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Central Mechanisms Regulating Coordinated Cardiovascular and Respiratory Function
Summary and Keywords
In response to changes in metabolic demand, the cardiovascular and respiratory systems are regulated in a highly coordinated fashion, such that both ventilation and cardiac output increase in a parallel fashion, thus maintaining a relatively constant level of arterial blood PO2, PCO2, and pH. In addition, external alerting stimuli that trigger defensive or orienting behavioral responses also trigger coordinated cardiorespiratory changes that are appropriate for the particular behavior. Furthermore, environmental challenges such as hypoxia or submersion evoke complex cardiovascular and respiratory response that have the effect of increasing oxygen uptake and/or conserving the available oxygen.
The brain mechanisms that are responsible for generating coordinated cardiorespiratory responses can be divided into reflex mechanisms and feedforward (central command) mechanisms. Reflexes that regulate cardiorespiratory function arise from a wide variety of internal receptors, and include those that signal changes in blood pressure, the level of blood oxygenation, respiratory activity, and metabolic activity. In most cases more than one reflex is activated, so that the ultimate cardiorespiratory response depends upon the interaction between different reflexes. The essential central pathways that subserve these reflexes are largely located within the brainstem and spinal cord, although they can be powerfully modulated by descending inputs arising from higher levels of the brain. The brain defense mechanisms that regulate the cardiorespiratory responses to external threatening stimuli (e.g., the sight, sound, or odor of a predator) are highly complex, and include both subcortical and cortical systems. The subcortical system, which includes the basal ganglia and midbrain colliculi as essential components, is phylogenetically ancient and generates immediate coordinated cardiorespiratory and motor responses to external stimuli. In contrast, the defense system that includes the cortex, hypothalamus, and limbic system evolved at a later time, and is better adapted to generating coordinated responses to external stimuli that involve cognitive appraisal.
Keywords: cardiorespiratory regulation, homeostasis, defensive behavior, chemoreceptor reflex, central respiratory neurons, hypothalamus, basal ganglia, medulla oblongata
Homeostasis requires highly coordinated cardiovascular and respiratory regulatory mechanisms to ensure that the delivery of oxygen to all regions of the body is sufficient to match the metabolic demands of each region. This is especially important in the case of the heart and skeletal muscles, whose metabolic activity can vary greatly. For example, during maximal exercise in humans, the oxygen delivery to exercising skeletal muscles can increase to levels 20- to 50-fold greater than resting levels (Sarelius & Pohl, 2010). This is achieved by a combination of local, autonomic, and respiratory mechanisms, as shown in Fig. 1. Local mechanisms, which include metabolic, endothelial, and myogenic components (Sarelius & Pohl, 2010) result in vasodilation in metabolically active skeletal muscle vascular beds, which increases the blood flow to the metabolically active region provided the arterial pressure is maintained. The arterial pressure in maintained as a consequence of (1) an increase in cardiac output, which results from a sympathetically mediated increase in heart rate and ventricular contractility; and (2) increases in sympathetic vasoconstrictor activity in regions where metabolic activity has not increased, such as the kidneys, gut. and resting skeletal muscles.
An increase in oxygen delivery to match an increase in oxygen consumption in a particular region also requires, apart from increased blood flow, maintenance of the oxygen content of the blood supply to the region. This is achieved by increasing respiratory rate and depth such that the increase in alveolar ventilation is sufficient to ensure that the pulmonary venous blood (and thus systemic arterial blood) is fully saturated with oxygen, despite the large increase in blood flow to the lungs (i.e., cardiac output) that occurs during exercise. It is remarkable that the arterial blood oxygen partial pressure (PaO2) remains little changed from resting levels, even during heavy exercise (Asmussen & Nielsen, 1960). The cardiovascular and respiratory regulatory mechanisms therefore achieve a close matching of cardiac output, ventilation, and oxygen consumption over a wide range of exercise intensities.
Respiratory and cardiovascular function is also regulated in a highly coordinated fashion in other circumstances, such as in association with behavioral responses that are critical for survival, for example, escape from a predator or pursuit of a prey. In addition, environmental challenges, such as hypoxia or heat stress, also require coordinated cardiovascular and respiratory responses to maintain homeostasis. Finally, such coordinated regulation is also evident even under resting conditions, as shown for example by respiratory-related variations in heart rate (respiratory sinus arrhythmia) or in the activity of sympathetic vasomotor nerves. In this article the central mechanisms that subserve coordinated cardiovascular and respiratory regulation under resting conditions will first be discussed. This will be followed by a discussion of the regulatory mechanisms that help to maintain homeostasis in response to the environmental challenges of hypoxia and heat stress, and then finally the central mechanisms regulating the cardiovascular and respiratory changes associated with defensive behavior.
Resting Conditions
Respiratory-Related Changes in Heart Rate
Variations in heart rate associated with the respiratory cycle (respiratory sinus arrhythmia) occur in many vertebrate species, from fish to mammals (Yasuma & Hayano, 2004). Typically the heart rate increases during inspiration and decreases during expiration (Ben-Tal et al., 2014; Eckberg, 2009; Yasuma & Hayano, 2004). The heart rate changes are due almost entirely to variations in cardiac vagal activity, and the magnitude of heart rate changes in respiratory sinus arrhythmia is sometimes used as a surrogate measure for cardiac vagal activity (Yasuma & Hayano, 2004). There is evidence from studies in both humans and animals that respiratory sinus arrhythmia improves the efficiency of pulmonary gas exchange by better matching of perfusion to ventilation in each respiratory cycle (Giardino, Glenny, Borson, & Chan, 2003; Hayano, Yasuma, Okado, Mukai, & Fujinami, 1996). In addition, it has also been proposed that respiratory sinus arrhythmia reduces the work of the heart while maintaining the same cardiac output and physiological levels of arterial carbon dioxide (Ben-Tal et al., 2014).
It is generally recognized that there are two major mechanisms that are responsible for the respiratory-related variations in cardiac vagal activity. First, cardiac vagal activity is inhibited during the inspiratory and late expiratory phase, as a consequence of inhibitory inputs to cardiac vagal preganglionic neurons in the nucleus ambiguus arising from central respiratory neurons (Gilbey, Jordan, Richter, & Spyer,1984; Silvani, Calandra-Buonara, Dampney, & Cortelli, 2016; Yasuma & Hayano, 2004). These inhibitory inputs have the effect of gating excitatory inputs to cardiac vagal preganglionic neurons arising from baroreceptors, chemoreceptors, and nasopharyngeal receptors (Davidson, Goldner, & McCloskey, 1976; Gandevia, McCloskey, & Potter, 1978; Gilbey et al., 1984; Haymet & McCloskey, 1975). Secondly, lung inflation during inspiration activates pulmonary stretch receptors innervated by C-fibers, leading to a reflex inhibition of cardiac vagal activity (Daly & Scott, 1958; Yasuma & Hayano, 2004).
It has been argued, however, that respiratory sinus arrhythmia, at least in humans, is due mainly to inputs from arterial baroreceptors, whose activity fluctuates with respiration as a consequence of respiratory-related changes in arterial pressure (Karemaker, 2009). While there is no doubt that respiration affects venous return and consequently cardiac output and arterial pressure, there are several reasons why the respiratory sinus arrhythmia observed in humans cannot be explained as a consequence of baroreceptor reflex effects, as discussed by Eckberg (2009). In particular, mechanical artificial ventilation that suppresses the activity of central respiratory neurons, but increases respiratory-related fluctuations in arterial pressure, greatly reduces respiratory sinus arrhythmia (Koh, Brown, Beightol, & Eckberg, 1998). Secondly, as shown in Fig. 2, when the magnitude of respiratory sinus arrhythmia is increased by slow deep breathing the heart rate increases before, not after, the increase in arterial pressure.
The precise source(s) of the inhibitory input(s) to cardiac vagal preganglionic neurons during inspiration is not known. There appear, however, to be at least two classes of inputs, which release GABA and glycine, respectively (Neff, Wang, Baxi, Evans, & Mendelowitz, 2003). The Bötzinger region within the ventral respiratory group in the medulla oblongata contains glycinergic neurons that are active during inspiration (Morgado-Valle, Baca, & Feldman, 2010), and so these could be the source of the glycinergic inhibitory input to cardiac vagal preganglionic neurons. The origin of the GABAergic inhibitory input to these neurons, however, is unknown.
Respiratory-Related Changes in Sympathetic Vasomotor Activity
The activity of virtually all sympathetic nerves innervating blood vessels displays respiratory-related fluctuations, although the precise pattern of respiratory modulation (i.e., whether firing is maximal during the inspiratory period or some other phase of the respiratory cycle) varies according to the vascular region, species of animal, and experimental conditions (Guyenet, 2011; Malpas, 1998). Sympathetic vasomotor nerves, with the exception of those innervating cutaneous blood vessels, also show a cardiac rhythm that is due to their reflex responsiveness to baroreceptor inputs that also have a cardiac pulsatile activity (Guyenet, 2011; Malpas, 1998). It has been suggested that the physiological advantage of the bursting pattern of firing in sympathetic nerves, whether it is related to the cardiac or respiratory cycle, is that it facilitates neuroeffector transmission, such that stronger vasomotor responses are elicited than would be the case if sympathetic nerves did not fire in bursts (Malpas, 1998).
The activity of sympathetic vasomotor nerves is driven largely by spinally projecting neurons in the rostral ventrolateral medulla (RVLM) (Dampney et al., 2003; Guyenet, 2006). These neurons, which consist of both adrenaline-synthesizing (C1) and non-C1 neurons (Dampney et al., 2003; Guyenet, 2006), include subsets of neurons that preferentially or exclusively project to sympathetic preganglionic neurons that regulate blood vessels in particular regions, such as the skin, skeletal muscle, or kidney (Dampney & McAllen, 1988; McAllen, May, & Campos, 1997). Furthermore, RVLM sympathetic premotor neurons display different patterns of respiratory-related activity, which are similar to those recorded in the sympathetic outflows to particular vascular beds (Guyenet, 2006). It therefore seems likely that the respiratory modulation of the activity of different sympathetic vasomotor nerves derives from their antecedent premotor neurons in the RVLM.
RVLM sympathetic premotor neurons receive both excitatory and inhibitory inputs from a variety of sources (Dampney et al., 2003; Guyenet, 2006). One of the major inhibitory inputs originates from GABAergic neurons within the caudal ventrolateral medulla (CVLM), and is a critical link in the central pathways mediating the baroreceptor reflex (Dampney et al., 2003; Guyenet, 2006). Neurons in the CVLM display a variety of respiratory patterns, some of which are opposite to those observed in RVLM sympathetic premotor neurons (Mandel & Schreihofer, 2006). Thus, the inputs from CVLM inhibitory neurons can account for the different patterns of respiratory modulation of RVLM neurons. The sources of inputs to the CVLM neurons that produce their respiratory modulation is unknown, but as pointed out by Guyenet (2011) they lie in close proximity to the pre-Bötzinger complex and adjacent rostral ventral respiratory group, both of which are key components of the central respiratory pattern generator.
Homeostatic Reflex Responses
Homeostasis is dependent, among other things, on reflexes that produce appropriate physiological responses to environmental challenges. In this section I shall consider particularly the central mechanisms that generate coordinated cardiovascular and respiratory reflex responses to such challenges, using hypoxia and heat stress as examples.
In arterial blood, over 95% of hemoglobin molecules are bound to oxygen, forming oxyhemoglobin, provided the arterial blood PO2 (PaO2) is greater than 90 mmHg. A decrease in arterial blood PO2 can occur when the atmospheric PO2 is reduced (e.g., at high altitudes), or when normal breathing is prevented, such as during submersion in diving animals or when a noxious substance (e.g., smoke) is encountered in the ambient air. The principal defense mechanism against hypoxia is the arterial chemoreceptor reflex, which when stimulated increases breathing (where that is possible) and simultaneously conserves the available oxygen. The chemoreceptors are located in the carotid and aortic bodies, and are activated primarily by a decrease in PaO2 and to a lesser extent by an increase in PaCO2 or a decrease in pH (Biscoe, Purves, & Sampson, 1970; Kumar & Prabahker, 2012).
As shown in Fig. 3, the reflex effects of hypoxic stimulation of the chemoreceptors are an increase in ventilation, due to increases in both the rate and depth of breathing, and cardiovascular effects, consisting of sympathetically mediated vasoconstriction in many vascular beds combined with vagally mediated bradycardia. The increase in ventilation allows oxygen uptake in the lungs to increase, while the reflexly evoked cardiovascular changes (vasoconstriction in skeletal muscle and visceral beds and bradycardia) tends to conserve the available oxygen.
It must be emphasized, however, that the chemoreceptor reflex is rarely, if ever, activated in isolation. For example, when hypoxia occurs under conditions where respiratory activity can increase, such as exposure to a high altitude, ventilation is reflexly increased, which in turn activates pulmonary stretch receptors, innervated by vagal afferent fibers. The pulmonary stretch receptor reflex tends to increase heart rate and decrease vascular resistance, thus opposing the primary cardiovascular reflex effects of chemoreceptor stimulation (Coleridge & Coleridge, 1994; Daly, Ward, & Wood, 1986). In contrast, when hypoxia occurs under conditions when respiratory activity cannot increase (such as during submersion or on exposure to a noxious substance), the primary reflex response to chemoreceptor stimulation is not opposed by secondary effects arising from pulmonary stretch receptor activation (Fig. 4). Instead, under such conditions, nasopharyngeal receptors may be stimulated, triggering the diving reflex. This reflex exists in all air-breathing vertebrates, but is particularly powerful in diving animals (Panneton, Gan, & Juric, 2010). Activation of the diving or nasopharyngeal reflex results in apnea, intense widespread peripheral vasoconstriction (except in the brain and heart), and a profound vagally mediated bradycardia (Fig. 4). The cardiovascular reflex effects conserve the available oxygen, which is thus preferentially provided to the brain and heart, two critical regions that cannot sustain an oxygen debt. In addition, the arterial hypoxia resulting from the reflexly evoked apnea will stimulate the arterial chemoreceptor reflex, thus reinforcing the vasoconstriction and bradycardia and further enhancing conservation of the available oxygen (Fig. 4).
In summary, the net effect of arterial hypoxia on cardiovascular and respiratory function depends upon interactions between several reflexes. The effect of such interactions between reflexes is that the pattern of reflexly evoked cardiovascular and respiratory responses is most appropriate for the particular environmental challenge.
The essential central pathways mediating the chemoreceptor reflex are shown in Fig 5. The chemoreceptor primary afferent fibers arising from the carotid and aortic bodies, which run in cranial nerves IX and X respectively, terminate on secondary interneurons in the nucleus of the tractus solitaries (NTS), primarily in the commissural and medial subnuclei (Finley & Katz, 1992). The primary chemoreceptor afferent fibers are probably glutamatergic (Guyenet, 2014; Vardhan, Kachroo, & Sapru, 1993) although it has been suggested that ATP may also have a role (Braga et al., 2007). The second-order neurons in the NTS that receive inputs from chemoreceptor afferent fibers do not receive inputs from baroreceptor or other types of sensory inputs; that is, there is little or no convergence of inputs from different receptor types to second-order NTS neurons (McDougall, Peters, & Andresen, 2009). There are direct projections from hypoxia-sensitive neurons in the commissural NTS to the RVLM (Hirooka, Polson, Potts, & Dampney, 1997) and also to the Kölliker-Fuse nucleus and lateral parabrachial nuclei in the dorsolateral pons (Song, Wang, Macdonald, & Poon, 2011). In addition, hypoxia-sensitive neurons in the Kölliker-Fuse nucleus project directly to the RVLM (Hirooka et al., 1997) (Fig. 5). Thus, signals from peripheral chemoreceptors may excite RVLM sympathetic premotor neurons by both direct and indirect routes from NTS neurons (Fig. 5). The hypoxia-sensitive neurons in the NTS that project directly to the RVLM, and those that project to the dorsolateral pons may arise from the same population of second-order chemosensitive neurons, which use glutamate as a neurotransmitter (Guyenet, 2014).
The increased sympathetic activity evoked by chemoreceptor stimulation occurs in respiratory-related bursts (Dick, Baekey, Paton, Lindsey, & Morris, 2009; Guyenet, 2014; Koshiya & Guyenet, 1996). After pontomedullary transection or blockade of central respiratory activity by inhibition of neurons in the ventral respiratory group, the bursting pattern of chemoreceptor-evoked sympathoexcitation is abolished but is replaced by tonic activation (Dick et al., 2009; Guyenet, 2014; Koshiya & Guyenet, 1996). Thus, it appears that tonic chemoreceptor-induced sympathoexcitation is mediated by the direct projection from NTS to RVLM sympathetic premotor neurons (Fig. 5), while the bursting pattern is mediated by the indirect pathway that includes neurons in the dorsolateral pons and ventrolateral medulla that are part of the central respiratory generator (Dick et al., 2009; Guyenet, 2014; Koshiya & Guyenet, 1996) (Fig. 5). It has been proposed that neurons in the central respiratory generator impose their respiratory-related bursting pattern on RVLM sympathetic premotor neurons via CVLM GABAergic neurons (Guyenet, 2014).
Chemoreceptor stimulation reflexly causes a vagally mediated bradycardia in the absence of secondary effects arising from increased respiratory activity, or when the stimulation is sufficiently intense so as to override secondary effects (McAllen, Salo, Paton, & Pickering, 2011). Such activity shows a respiratory modulation, such that it occurs primarily during the post-inspiratory and expiratory phase (McAllen et al., 2011). The reduced activity during the inspiratory phase is explained by respiratory gating as discussed above (see section Respiratory-Related Changes in Heart Rate), such that inputs to cardiac vagal preganglionic neurons in the nucleus ambiguus arising from chemoreceptors (and other peripheral receptors) are inhibited by inputs either from central respiratory neurons or from pulmonary stretch receptors (Davidson, Goldner, & McCloskey, 1976; Gandevia, McCloskey, & Potter, 1978). The site at which such gating occurs, at least in the case of inputs from pulmonary stretch receptors, is unlikely to be in the NTS, because as mentioned above, inputs from chemoreceptor and pulmonary stretch receptor afferents synapse with different neurons in the NTS. It is more likely that gating occurs in the nucleus ambiguus itself, because this nucleus receives direct inputs from the medial subnucleus of the NTS (Stuesse & Fish, 1984), one of the main sites of termination of primary chemoreceptor afferent fibers (Finley & Katz, 1992), as well as respiratory-related inputs (McAllen et al., 2011). The chemoreceptor-evoked excitation of cardiac vagal preganglionic neurons that occurs during the post-inspiratory and expiratory phase is presumably driven by the direct input from the medial NTS.
The receptors triggering the diving or nasopharyngeal reflex are innervated by trigeminal nerve afferents that terminate in the spinal trigeminal nucleus (Panneton, 2013), which in turn projects to various targets including the medial NTS, RVLM, and Kölliker-Fuse nucleus in the dorsolateral pons (Panneton et al., 2010). The medial NTS, which projects directly to the RVLM, is critical for the expression of the sympathoexcitatory component of the response (Dutschmann & Herbert, 1998b). In contrast, the Kölliker-Fuse nucleus is essential for the expression of the reflex apnea and bradycardia but not sympathoexcitation (Dutschmann & Herbert, 1998a). Thus, descending pathways from the Kölliker-Fuse nucleus to medullary respiratory neurons and cardiac vagal preganglionic neurons may mediate the reflex apnea and bradycardia, respectively. Alternatively, as suggested by Guyenet (2011), it is possible that the reflex bradycardia is secondary to the apnea, that is, it is caused by removal of the inhibition of cardiac vagal preganglionic neurons by central respiratory neurons that are responsible for respiratory sinus arrhythmia (see section on Respiratory-Related Changes in Heart Rate). In any case, it is clear that the inhibitory influence of the Kölliker-Fuse nucleus on respiration is sufficiently powerful to completely suppress respiratory activity during diving, even though the resultant arterial hypoxia would activate peripheral chemoreceptors.
Heat Stress
Maintenance of a core body temperature within narrow limits is essential for survival in mammals, and highly effective regulatory mechanisms have evolved that enable mammals to conserve and generate heat in response to cold stress, and increase heat loss in response to heat stress. The compensatory response to heat stress, in particular, requires a close coordination of cardiovascular and respiratory reflex responses.
An increase in ambient temperature is detected by warm receptors in the skin, and leads to cutaneous vasodilation, due to inhibition of sympathetic vasoconstrictor activity and excitation of sympathetic vasodilator activity (Kellogg, 2006; Morrison & Nakamura, 2011; Rowell, 1974). In humans and other mammals with sweat glands, sympathetic sudomotor activity is reflexly increased, causing increased sweat production and consequent increased evaporative heat loss from the skin. In mammals that lack sweat glands, evaporative cooling is achieved primarily by panting, which is characterized by rapid shallow breathing (Morrison & Nakamura, 2011). Even in non-panting animals such as humans, respiratory activity is altered, most typically by an increase in tidal volume (Saxton, 1975).
Afferent fibers conveying signals from warm receptors terminate in the dorsal column of the spinal cord, from which an ascending pathway conveys warm signals to the median preoptic nucleus (MnPO) in the hypothalamus, via a relay in the dorsolateral subnucleus of the lateral parabrachial nucleus (dlPB) (Fig. 6). The neurons in the MnPO that receive these inputs project to and excite neurons in the median preoptic nucleus (MPO) that inhibit the sympathetic premotor neurons in the raphe pallidus (RP) in the midline medulla that produce skin vasoconstriction and thermogenesis in brown adipose tissue, both directly and via the DMH (Fig. 6) (McKinley et al., 2015).
In animals such as dogs that normally pant in response to heat stress, localized heating in the preoptic area in the hypothalamus that includes the MnPO results in panting (Boulant, 1981; Kronert & Pleschka, 1976). Furthermore, the onset of panting in dogs is accompanied by a large increase in lingual blood flow, whether induced by increased ambient temperature or localized heating of the preoptic area (Kronert & Pleschka, 1976). The combination of panting and increased lingual blood flow greatly increases evaporative heat loss, and the fact that they occur simultaneously suggests that both are driven by a common central mechanism within the preoptic area. In contrast to the cardiovascular responses to heat stress, however, very little is known about the central pathways that mediate the respiratory responses, apart from the fact that in both cases the MnPO plays a critical role (Fig. 6).
Central Cardiovascular and Respiratory Regulation Associated With Defensive Behavior
The ability of an animal to respond rapidly and appropriately to threatening or potentially threatening stimuli in its environment is critical for survival. In the case of predators, the ability to respond appropriately to the presence of prey is equally critical. An appropriate response includes both behavioral responses (e.g., escape or pursuit) supported by cardiovascular and respiratory changes that meet the metabolic demands associated with the particular behavior. In this section the coordinated cardiovascular and respiratory changes that are triggered by alerting or potentially threatening stimuli will be summarized first, followed by a discussion of the brain mechanisms that subserve these responses.
Brief alerting stimuli such as an unexpected noise evokes immediate autonomic and respiratory responses, characterized by strong cutaneous vasoconstriction and respiratory activation, but without significant effects on the mesenteric, renal, and hindlimb vascular beds (Bondarenko, Averell, Hodgson, & Nalivaiko, 2013; Mohammed, Kulasekera, de Menezes, Ootsuka, & Blessing, 2013; Yu & Blessing, 2011). This initial response to a novel alerting stimuli may lead to what is often called a defense reaction if the stimulus is prolonged or more threatening (Casto et al., 1989). More prolonged threatening stimuli typically elicit a more complex autonomic response, which is characterized by a differentiated pattern of sympathetic responses, with increases in arterial pressure, heart rate, adrenaline release, and sympathetically mediated vasoconstriction in skin, renal, and mesenteric beds, but with highly variable effects on skeletal muscle sympathetic activity (for a more detailed discussion see Dampney (2015)). During naturally evoked psychological stress the baroreflex control of sympathetic vasomotor activity is reset, such that both the arterial pressure and sympathetic vasomotor activity are regulated over a higher operating range, without any decrease in reflex gain (Kanbar, Orea, Varres, & Julien, 2007). These autonomic responses are accompanied by an increased respiratory rate and ventilation (Bondarenko, Beig, Hodgson, Braga, & Nalivaiko, 2015; Bondarenko, Hodgson, & Nalivaiko, 2014; Suess, Alexander, Smith, Sweeney, & Marion, 1980).
All levels of the brain, from the medulla oblongata to the cortex, play a role in generating cardiovascular and respiratory responses to alerting or threatening stimuli. In regard to the mechanisms that produce highly synchronized and coordinated cardiovascular and respiratory responses, there is clear evidence that three regions have a pivotal role: the dorsomedial hypothalamus (DMH) and adjacent perifornical area (PeF), the midbrain periaqueductal gray (PAG), and midbrain colliculi. The DMH/PeF receives inputs from several forebrain regions, including the cortex and amygdala, and is well adapted to generating appropriate responses to sustained threatening stimuli that involve cognitive appraisal (Dampney, 2015). In contrast, the midbrain colliculi is part of a subcortical defense system that also includes the basal ganglia and which produces immediate stereotyped response to alerting stimuli (that may be visual, auditory, or somatosensory) (Müller-Ribeiro, Goodchild, McMullan, Fontes, & Dampney, 2016). The basal ganglia/colliculi system is phylogenetically ancient, going back to the beginning of vertebrate evolution 560 million years ago (Grillner & Robertson, 2015). In the following sections the mechanisms by which each of these different defense systems produce coordinated cardiovascular and respiratory responses will be discussed separately.
The Basal Ganglia/Colliculi Defense System
As shown in Fig. 7, the superior colliculus (also called the optic tectum in non-mammalian vertebrates) receives inputs arising from visual, auditory, and somatosensory stimuli, and can generate different patterns of highly coordinated behavioral responses, including orienting, defensive, or escape responses, via their descending projections to the brainstem and spinal cord (Dean, Redgrave, & Westby, 1989).
The collicular neurons that generate such coordinated responses are normally inhibited by tonic GABAergic inputs, which arise from the substantia nigra pars reticulata (Coimbra & Brandao, 1993) (Fig. 7). The substantia nigra pars reticulata itself receives inhibitory inputs from the striatum that in turn receives inputs from the thalamus as well as from the cortex and amygdala (McHaffie, Stanford, Stein, Coizet, & Redgrave, 2005) (Fig. 7). There are also projections back from the superior colliculus to the striatum, relayed via the thalamus (Fig. 7). The substantia nigra pars reticulata and striatum are components of the basal ganglia, and it has been proposed that this loop involving the basal ganglia and superior colliculus allows selection of an appropriate response to competing inputs, including those that arise from the cortex (McHaffie et al., 2005). In other words, the striatum acts as an "action selector," so that the most appropriate behavioral response can be selected, according to the inputs into the striatum. Such selection is achieved by withdrawing inhibition from the particular output neurons in the superior colliculus that regulate the appropriate behavioral response.
It should be emphasized that although there are inputs to the striatum from the cortex and amygdala (Fig. 7), highly coordinated behavioral responses to external stimuli can still be elicited even when such inputs are removed (Grillner & Robertson, 2015). That is, the basal ganglia/colliculi system is sufficient to produce complex behaviors, consistent with the fact that this system evolved very early in vertebrate evolution, before the development of the cerebral cortex.
Most studies of the role of the basal ganglia/colliculi system in generating behavioral responses have focused on the somatomotor components of such responses. Recently, however, it has been shown that in anesthetized rats natural auditory, visual, and somatosensory stimuli could evoke, in addition to somatomotor responses, increases in sympathetic and respiratory activity, but only after disinhibition (by microinjection of the GABA receptor antagonists picrotoxin or bicuculline) of certain sites within the midbrain colliculi (Müller-Ribeiro, Dampney, McMullan, Fontes, & Goodchild, 2014) (Fig. 8A). These effects were still observed after removal of the cerebral cortex and amygdala, and thus were independent of inputs from the cortex and amygdala (Müller-Ribeiro et al., 2014). Taken together with previous studies of the role of the basal ganglia/colliculi system in somatomotor control and behavior, these findings suggest that this system generates appropriate cardiovascular and respiratory responses to support the stereotyped behavioral responses evoked by auditory, visual, and somatosensory stimuli inputs to the colliculi (Fig. 7).
A remarkable feature of the sympathetic, respiratory, and somatomotor responses evoked by visual, auditory, and somatosensory stimuli following disinhibition of sites within the colliculi is that the responses are highly synchronized (e.g., Fig. 8A), suggesting the hypothesis that all these responses are driven by a common population of command neurons that are activated by these different inputs, as shown in Fig. 8B (Müller-Ribeiro et al., 2014). Consistent with this hypothesis, many neurons within the deep layers of the superior colliculus receive convergent visual, auditory, and somatosensory inputs, and also have descending projections to the brain stem (Meredith & Stein, 1986).
An alternative hypothesis to explain the synchrony between respiratory and sympathetic responses generated from the colliculi is that the collicular neurons project to respiratory neurons in the brain stem that in turn provide an input to sympathetic premotor neurons. In fact, such coupling does occur at the level of the brain stem (see Respiratory-Related Changes in Sympathetic Vasomotor Activity). This alternative hypothesis is highly unlikely, however, because the pattern of respiratory modulation of sympathetic activity that occurs at the level of the brain stem is distinctly different from that evoked by activation of collicular neurons. In particular, under resting conditions splanchnic sympathetic activity is increased during the expiratory phase (Dick, Hsieh, Morrison, Coles, & Prabhakar, 2004), whereas after collicular disinhibition the increase in splanchnic sympathetic activity evoked by auditory, visual, or somatosensory stimuli occurs primarily during the inspiratory phase of respiration (i.e., when phrenic nerve activity is increased) (Müller-Ribeiro et al., 2014) (Fig. 8A). It therefore seems more likely that the synchronized sympathetic and respiratory responses that can be evoked after collicular disinhibition are driven by the same population of collicular neurons. It is conceivable that these same neurons may also generate stereotyped behavioral responses from the colliculi, such as orienting or escape. In that case, the simultaneously evoked cardiovascular and respiratory effects are presumably appropriate for the particular behavioral response.
The DMH/PeF Defense System
As shown in Fig. 9, the DMH/PeF receives inputs from neurons in the prefrontal cortex, amygdala, and PAG, and projects directly and indirectly to other nuclei that regulate ACTH and vasopressin release, and cardiovascular and respiratory activity. The critical importance of this region in mediating stress-evoked cardiovascular and respiratory responses is well-established. First, inhibition of neurons within the DMH/PeF greatly reduces the cardiovascular, neuroendocrine, and respiratory responses to psychological stressors (Bondarenko et al., 2015; DiMicco, Samuels, Zaretskaia, & Zaretsky, 2002). Second, activation of neurons in the DMH/PeF evokes cardiovascular and respiratory responses that are very similar to naturally evoked stress responses (DiMicco et al., 2002; Fontes, Tagawa, Polson, Cavanagh, & Dampney, 2001; Horiuchi et al., 2004; McDowall, Horiuchi, & Dampney, 2007; McDowall, Horiuchi, Killinger, & Dampney, 2006). Finally, psychological stress evokes a marked increase in c-Fos expression in the DMH/PeF (Furlong, McDowall, Horiuchi, Polson, & Dampney, 2014; Spencer & Day, 2004).
The fact that cardiovascular and respiratory changes are evoked by activation of DMH/PeF neurons raises the question as to whether both responses are driven from the same population of neurons. There is little correlation, however, between the magnitude of respiratory responses (measured as changes in phrenic nerve activity) or cardiovascular responses (measured as changes in renal or cutaneous sympathetic activity) when different sites in the DMH/PeF are activated (McDowall et al., 2007; Tanaka & McAllen, 2008). It therefore can be concluded that the increased sympathetic and respiratory activities that are evoked by activation of DMH/PeF neurons are mediated by separate descending pathways (Fig. 9). These descending pathways, however, have not been clearly defined, except for a direct projection from the DMH to the raphe pallidus in the midline medulla that regulates heart rate (Fig. 9) (Dampney, 2015).
Lesions or inhibition of neurons in the amygdala reduce both the cardiovascular and respiratory responses to psychological stress (Bondarenko et al., 2014; McDougall, Widdop, & Lawrence, 2005). The amygdala is also the source of one of the major inputs to the DMH/PeF (Dampney, 2015) (Fig. 9), and so it seems likely that the input from the amygdala is a major component of the central pathways driving cardiovascular and respiratory responses to psychological stress. An additional input to the DMH/PeF that also may also contribute to these responses arises from the dorsolateral part of the PAG (Horiuchi, McDowall, & Dampney, 2009).
Survival of an animal depends on regulating the delivery of oxygen to all regions of the body so as to match the metabolic requirements of each region. That in turn depends upon a close coordination of central cardiovascular and respiratory mechanisms. Such coordination results from three general mechanisms: (1) reflexes that simultaneously regulate both cardiovascular and respiratory function in response to inputs from peripheral receptors, such as chemoreceptors, nasopharyngeal receptors, or warm receptors; (2) central connections between neurons regulating respiratory activity and those regulating cardiovascular function; and (3) central command, whereby neurons at higher levels of the brain have collateral projections to both cardiovascular and respiratory neurons within the brain stem. In many cases two or more of these mechanisms may contribute to the coordination of cardiovascular and respiratory function, together with local mechanisms that are also required to ensure that blood flow to particular regions, especially the skeletal muscles and heart, matches the metabolic demands of those regions.
While much progress has been in identifying and unraveling the central cardiovascular and respiratory mechanisms, there is still much that is not understood. For example, while it is generally agreed that central command has a critical role in regulating cardiovascular and respiratory function in exercise (Forster, Haouzi, & Dempsey, 2012; Williamson, Fadel, & Mitchell, 2006), very little is known about the central pathways that subserve central command in exercise. Future studies will be needed to address these important unanswered questions.
Asmussen, E., & Nielsen, M. (1960). Alveolo-arterial gas exchange at rest and during work at different 02 tensions. Acta Physiologica Scandinavica, 50, 153–166.Find this resource:
Ben-Tal, A., Shamailov, S. S., & Paton, J. F. (2014). Central regulation of heart rate and the appearance of respiratory sinus arrhythmia: New insights from mathematical modeling. Mathematical Biosciences, 255, 71–82.Find this resource:
Biscoe, T. J., Purves, M. J., & Sampson, S. R. (1970). The frequency of nerve impulses in single carotid body chemoreceptor afferent fibres recorded in vivo with intact circulation. Journal of Physiology, 208, 121–131.Find this resource:
Bondarenko, E., Averell, L., Hodgson, D. M., & Nalivaiko, E. (2013). Neuronal network mediating respiratory activation in response to alerting stimuli and stress. Autonomic Neuroscience, 177, 37–38.Find this resource:
Bondarenko, E., Beig, M. I., Hodgson, D. M., Braga, V. A., & Nalivaiko, E. (2015). Blockade of the dorsomedial hypothalamus and the perifornical area inhibits respiratory responses to arousing and stressful stimuli. American Journal of Physiology Regulatory Integrative and Comparative Physiology, 308, R816–R822.Find this resource:
Bondarenko, E., Hodgson, D. M., & Nalivaiko, E. (2014). Amygdala mediates respiratory responses to sudden arousing stimuli and to restraint stress in rats. American Journal of Physiology Regulatory Integrative and Comparative Physiology, 306, R951–R959.Find this resource:
Boulant, J. A. (1981). Hypothalamic mechanisms in thermoregulation. Federation Proceedings, 40, 2843–2850.Find this resource:
Braga, V. A., Soriano, R. N., Braccialli, A. L., De Paula, P. M., Bonagamba, L. G., Paton, J. F., & Machado, B. H. (2007). Involvement of L-glutamate and ATP in the neurotransmission of the sympathoexcitatory component of the chemoreflex in the commissural nucleus tractus solitarii of awake rats and in the working heart-brainstem preparation. Journal of Physiology, 581, 1129–1145.Find this resource:
Casto, R., Nguyen, T., & Printz, M. P. (1989). Characterization of cardiovascular and behavioral responses to alerting stimuli in rats. American Journal of Physiology Regulatory Integrative and Comparative Physiology, 256, R1121–R1126.Find this resource:
Coimbra, N. C., & Brandao, M. L. (1993). GABAergic nigro-collicular pathways modulate the defensive behaviour elicited by midbrain tectum stimulation. Behavioral Brain Research, 59, 131–139.Find this resource:
Coleridge, H. M., & Coleridge, J. C. (1994). Pulmonary reflexes: Neural mechanisms of pulmonary defense. Annual Review of Physiology, 56, 69–91.Find this resource:
Daly, M. de B., & Scott, M. J. (1958). The effects of stimulation of the carotid body chemoreceptors on heart rate in the dog. Journal of Physiology, 144, 148–166.Find this resource:
Daly, M. de B., Ward, J., & Wood, L. M. (1986). Modification by lung inflation of the vascular responses from the carotid body chemoreceptors and other receptors in dogs. Journal of Physiology, 378, 13–30.Find this resource:
Dampney, R. A. L. (2008). Cardiovascular and respiratory reflexes: Physiology and pharmacology. In P. Low & E. Benarroch (Eds.), Clinical autonomic disorders (pp. 43–56). Philadelphia: Lippincott Williams & Wilkins.Find this resource:
Dampney, R. A. L. (2015). 2013 Carl Ludwig Distinguished Lectureship of the APS Neural Control and Autonomic Regulation Section: Central mechanisms regulating coordinated cardiovascular and respiratory function during stress and arousal. American Journal of Physiology Regulatory Integrative and Comparative Physiology, 309, R429–R443.Find this resource:
Dampney, R. A. L. (2016). Central neural control of the cardiovascular system: Current perspectives. Advances in Physiology Education, 40, 283–296.Find this resource:
Dampney, R. A. L., Coleman, M. J., Fontes, M. A. P., Hirooka, Y., Horiuchi, J., Li, Y.-W., … Tagawa, T. (2002). Mechanisms underlying short- and long-term regulation of the cardiovascular system. Clinical and Experimental Phatmacology and Physiology, 29, 261–268.Find this resource:
Dampney, R. A. L., Horiuchi, J., Tagawa, T., Fontes, M. A. P., Potts, P. D., & Polson, J. W. (2003). Medullary and supramedullary mechanisms regulating sympathetic vasomotor tone. Acta Physiologica Scandinavica, 177, 209–218.Find this resource:
Dampney, R. A. L., & McAllen, R. M. (1988). Differential control of sympathetic fibres supplying hindlimb skin and muscle by subretrofacial neurones in the cat. Journal of Physiology, 395, 41–56.Find this resource:
Davidson, N. S., Goldner, S., & McCloskey, D. I. (1976). Respiratory modulation of baroreceptor and chemoreceptor reflexes affecting heart rate and cardiac vagal efferent nerve activity. Journal of Physiology, 259, 523–530.Find this resource:
Dean, P., Redgrave, P., & Westby, G. W. (1989). Event or emergency? Two response systems in the mammalian superior colliculus. Trends in Neuroscience, 12, 137–147.Find this resource:
Dick, T. E., Baekey, D. M., Paton, J. F., Lindsey, B. G., & Morris, K. F. (2009). Cardio-respiratory coupling depends on the pons. Respiratory Physiology and Neurobiology, 168, 76–85.Find this resource:
Dick, T. E., Hsieh, Y. H., Morrison, S. F., Coles, S. K., & Prabhakar, N. (2004). Entrainment pattern between sympathetic and phrenic nerve activities in the Sprague-Dawley rat: Hypoxia-evoked sympathetic activity during expiration. American Journal of Physiology Regulatory Integrative and Comparative Physiology, 286, R1121–R1128.Find this resource:
DiMicco, J. A., Samuels, B. C., Zaretskaia, M. V., & Zaretsky, D. V. (2002). The dorsomedial hypothalamus and the response to stress: Part renaissance, part revolution. Pharmacology, Biochemistry and Behavior, 71, 469–480.Find this resource:
Dutschmann, M., & Herbert, H. (1998a). NMDA and GABAA receptors in the rat Kolliker-Fuse area control cardiorespiratory responses evoked by trigeminal ethmoidal nerve stimulation. Journal of Physiology, 510, 793–804.Find this resource:
Dutschmann, M., & Herbert, H. (1998b). The medial nucleus of the solitary tract mediates the trigeminally evoked pressor response. Neuroreport, 9, 1053–1057.Find this resource:
Eckberg, D. L. (2009). Point:counterpoint: Respiratory sinus arrhythmia is due to a central mechanism vs. respiratory sinus arrhythmia is due to the baroreflex mechanism. Journal of Applied Physiology, 106, 1740–1742.Find this resource:
Finley, J. C. W., & Katz, D. M. (1992). The central organization of carotid body afferent projections to the brainstem of the rat. Brain Research, 572, 108–116.Find this resource:
Fontes, M. A. P., Tagawa, T., Polson, J. W., Cavanagh, S. J., & Dampney, R. A. L. (2001). Descending pathways mediating cardiovascular response from dorsomedial hypothalamic nucleus. American Journal of Physiology Heart and Circulatory Physiology, 280, H2891–H2901.Find this resource:
Forster, H. V., Haouzi, P., & Dempsey, J. A. (2012). Control of breathing during exercise. Comprehensive Physiology, 2, 743–777.Find this resource:
Furlong, T. M., McDowall, L. M., Horiuchi, J., Polson, J. W., & Dampney, R. A. L. (2014). The effect of air puff stress on c-Fos expression in rat hypothalamus and brainstem: Central circuitry mediating sympathoexcitation and baroreflex resetting. European Journal of Neuroscience, 39, 1429–1438.Find this resource:
Gandevia, S. C., McCloskey, D. I., & Potter, E. K. (1978). Reflex bradycardia occurring in response to diving, nasopharyngeal stimulation and ocular pressure, and its modification by respiration and swallowing. Journal of Physiology, 276, 383–394.Find this resource:
Giardino, N. D., Glenny, R. W., Borson, S., & Chan, L. (2003). Respiratory sinus arrhythmia is associated with efficiency of pulmonary gas exchange in healthy humans. American Journal of Physiology Heart and Circulatory Physiology, 284, H1585–H1591.Find this resource:
Gilbey, M. P., Jordan, D., Richter, D. W., & Spyer, K. M. (1984). Synaptic mechanisms involved in the inspiratory modulation of vagal cardio-inhibitory neurones in the cat. Journal of Physiology, 356, 65–78.Find this resource:
Grillner, S., & Robertson, B. (2015). The basal ganglia downstream control of brainstem motor centres – an evolutionarily conserved strategy. Current Opinion in Neurobiology, 33, 47–52.Find this resource:
Guyenet, P. G. (2006). The sympathetic control of blood pressure. Nature Reviews Neuroscience, 7, 335–346.Find this resource:
Guyenet, P. G. (2011). Cardiorespiratory integration. In I. J. Llewellyn-Smith & A. J. M. Verbene (Eds.), Central regulation of autonomic functions (pp. 180–201). New York: Oxford University Press.Find this resource:
Guyenet, P. G. (2014). Regulation of breathing and autonomic outflows by chemoreceptors. Comprehensive Physiology, 4, 1511–1562.Find this resource:
Hayano, J., Yasuma, F., Okada, A., Mukai, S., & Fujinami, T. (1996). Respiratory sinus arrhythmia. A phenomenon improving pulmonary gas exchange and circulatory efficiency. Circulation, 94, 842–847.Find this resource:
Haymet, B. T., & McCloskey, D. I. (1975). Baroreceptor and chemoreceptor influence on heart rate during the respiratory cycle in the dog. Journal of Physiology, 245, 699–712.Find this resource:
Hirooka, Y., Polson, J. W., Potts, P. D., & Dampney, R. A. L. (1997). Hypoxia-induced Fos expression in neurons projecting to the pressor region in the rostral ventrolateral medulla. Neuroscience, 80, 1209–1224.Find this resource:
Horiuchi, J., McAllen, R. M., Allen, A. M., Killinger, S., Fontes, M. A. P., & Dampney, R. A. L. (2004). Descending vasomotor pathways from the dorsomedial hypothalamic nucleus: Role of medullary raphe and RVLM. American Journal of Physiology Regulatory Integrative and Comparative Physiology, 287, R824–R832.Find this resource:
Horiuchi, J., McDowall, L. M., & Dampney, R. A. L. (2009). Vasomotor and respiratory responses evoked from the dorsolateral PAG are mediated by the dorsomedial hypothalamus. Journal of Physiology, 587, 5149–5162.Find this resource:
Kanbar, R., Orea, V., Barres, C., & Julien, C. (2007). Baroreflex control of renal sympathetic nerve activity during air-jet stress in rats. American Journal of Physiology Regulatory Integrative and Comparative Physiology, 292, R362–R367.Find this resource:
Karemaker, J. M. (2009). Counterpoint: Respiratory sinus arrhythmia is due to the baroreflex mechanism. Journal of Applied Physiology, 106, 1742–1743.Find this resource:
Kellogg, D. L. (2006). In vivo mechanisms of cutaneous vasodilation and vasoconstriction in humans during thermoregulatory challenges. Journal of Applied Physiology, 100, 1709–1718.Find this resource:
Koh, J., Brown, T. E., Beightol, L. A., & Eckberg, D.L. (1998). Contributions of tidal lung inflation to human R-R interval and arterial pressure fluctuations. Journal of the Autonomic Nervous System, 68, 89–95.Find this resource:
Koshiya, N., & Guyenet, P. G. (1996). Tonic sympathetic chemoreflex after blockade of respiratory rhythmogenesis in the rat. Journal of Physiology, 491, 859–869.Find this resource:
Kronert, H., & Pleschka, K. (1976). Lingual blood flow and its hypothalamic control in the dog during panting. Pflügers Archives, 367, 25–31.Find this resource:
Kumar, P., & Prabhakar, N. R. (2012). Peripheral chemoreceptors: Function and plasticity of the carotid body. Comprehensive Physiology, 2, 141–219.Find this resource:
Malpas, S. C. (1998). The rhythmicity of sympathetic nerve activity. Progress in Neurobiology, 56(1), 65–96.Find this resource:
Mandel, D. A., & Schreihofer, A. M. (2006). Central respiratory modulation of barosensitive neurones in rat caudal ventrolateral medulla. Journal of Physiology, 572, 881–896.Find this resource:
McAllen, R. M., May, C. N., & Campos, R. R. (1997). The supply of vasomotor drive to individual classes of sympathetic neuron. Clinical and Experimental Hypertension, 19, 607–618.Find this resource:
McAllen, R. M., Salo, L. M., Paton, J. F., & Pickering, A. E. (2011). Processing of central and reflex vagal drives by rat cardiac ganglion neurones: An intracellular analysis. Journal of Physiology, 589, 5801–5818.Find this resource:
McDougall, S. J., Peters, J. H., & Andresen, M. C. (2009). Convergence of cranial visceral afferents within the solitary tract nucleus. Journal of Neuroscience, 29, 12886–12895.Find this resource:
McDougall, S. J., Widdop, R. E., & Lawrence, A. J. (2005). Central autonomic integration of psychological stressors. Focus on cardiovascular modulation. Autonomic Neuroscience, 123, 1–11.Find this resource:
McDowall, L. M., Horiuchi, J., & Dampney, R. A. L. (2007). Effects of disinhibition of neurons in the dorsomedial hypothalamus on central respiratory drive. American Journal of Physiology Regulatory Integrative and Comparative Physiology, 293, R1728–R1735.Find this resource:
McDowall, L. M., Horiuchi, J., Killinger, S., & Dampney, R. A. L. (2006). Modulation of the baroreceptor reflex by the dorsomedial hypothalamic nucleus and perifornical area. American Journal of Physiology Regulatory Integrative and Comparative Physiology, 290, R1020–R1026.Find this resource:
McHaffie, J. G., Stanford, T. R., Stein, B. E., Coizet, V., & Redgrave, P. (2005). Subcortical loops through the basal ganglia. Trends in Neuroscience, 28, 401–407.Find this resource:
McKinley, M. J., Yao, S. T., Uschakov, A., McAllen, R. M., Rundgren, M., & Martelli, D. (2015). The median preoptic nucleus: Front and centre for regulation of body fluid, sodium, temperature, sleep and cardiovascular homeostasis. Acta Physiologica, 214, 8–32.Find this resource:
Meredith, M. A., & Stein, B. E. (1986). Visual, auditory, and somatosensory convergence on cells in superior colliculus results in multisensory integration. Journal of Neurophysiology, 56, 640–662.Find this resource:
Mohammed, M., Kulasekara, K., de Menezes, R. C., Ootsuka Y., & Blessing, W. W. (2013). Inactivation of neuronal function in the amygdaloid region reduces tail artery blood flow alerting responses in conscious rats. Neuroscience, 228, 13–22.Find this resource:
Morgado-Valle, C., Baca, S. M., & Feldman, J. L. (2010). Glycinergic pacemaker neurons in pre-Bötzinger complex of neonatal mouse. Journal of Neuroscience, 30, 3634–3639.Find this resource:
Morrison, S. F., & Nakamura, K. (2011). Central neural pathways for thermoregulation. Frontiers in Biosciences, 16, 74–104.Find this resource:
Müller-Ribeiro, F. C. F., Dampney, R. A. L., McMullan, S., Fontes, M. A. P., & Goodchild, A. K. (2014). Disinhibition of the midbrain colliculi unmasks coordinated autonomic, respiratory, and somatomotor responses to auditory and visual stimuli. American Journal of Physiology Regulatory Integrative and Comparative Physiology, 307, R1025–R1035.Find this resource:
Müller-Ribeiro, F. C. F., Goodchild, A. K., McMullan, S., Fontes, M. A. P., & Dampney, R. A. L. (2016). Coordinated autonomic and respiratory responses evoked by alerting stimuli: Role of the midbrain colliculi. Respiratory Physiology and Neurobiology, 226, 87–93.Find this resource:
Neff, R. A., Wang, J., Baxi, S., Evans, C., & Mendelowitz, D. (2003). Respiratory sinus arrhythmia: Endogenous activation of nicotinic receptors mediates respiratory modulation of brainstem cardioinhibitory parasympathetic neurons. Circulation Research, 93, 565–572.Find this resource:
Panneton, W. M. (2013). The mammalian diving response: An enigmatic reflex to preserve life? Physiology, 28, 284–297.Find this resource:
Panneton, W. M., Gan, Q., & Juric, R. (2010). The rat: A laboratory model for studies of the diving response. Journal of Applied Physiology, 108, 811–820.Find this resource:
Rowell, L. B. (1974). Human cardiovascular adjustments to exercise and thermal stress. Physiological Reviews, 54, 75–159.Find this resource:
Sarelius, I., & Pohl, U. (2010). Control of muscle blood flow during exercise: Local factors and integrative mechanisms. Acta Physiologica, 199, 349–365.Find this resource:
Saxton, C. (1975). Respiration during heat stress. Aviation Space Environmental Medicine, 46, 41–46.Find this resource:
Silvani, A., Calandra-Buonara, G., Dampney, R. A. L., & Cortelli, P. (2016). Brain-heart interactions: Physiology and clinical implications. Philosophical Transactions of the Royal Society, A 374, 20150181.Find this resource:
Song, G., Xu, H., Wang, H., Macdonald, S. M., & Poon, C. S. (2011). Hypoxia-excited neurons in NTS send axonal projections to Kolliker-Fuse/parabrachial complex in dorsolateral pons. Neuroscience, 175, 145–153.Find this resource:
Spencer, S. J., & Day, T. A. (2004). Role of catecholaminergic inputs to the medial prefrontal cortex in local and subcortical expression of Fos after psychological stress. Journal of Neuroscience Research, 78, 279–288.Find this resource:
Stuesse, S. L., & Fish, S. E. (1984). Projections to the cardioinhibitory region of the nucleus ambiguus of rat. Journal of Comparative Neurology, 229, 271–278.Find this resource:
Suess, W. M., Alexander, A. B., Smith, D. D., Sweeney, H. W., & Marion, R. J. (1980). The effects of psychological stress on respiration: A preliminary study of anxiety and hyperventilation. Psychophysiology, 17, 535–540.Find this resource:
Tanaka, M., & McAllen, R. M. (2008). Functional topography of the dorsomedial hypothalamus. American Journal of Physiology Regulatory Integrative and Comparative Physiology, 294, R477–R486.Find this resource:
Vardhan, A., Kachroo, A., & Sapru, H. N. (1993). Excitatory amino acid receptors in commissural nucleus of the NTS mediate carotid chemoreceptor responses. American Journal of Physiology Regulatory Integrative and Comparative Physiology, 264, R41–R50.Find this resource:
Williamson, J. W., Fadel, P. J., & Mitchell, J. H. (2006). New insights into central cardiovascular control during exercise in humans: A central command update. Experimental Physiology, 91, 51–58.Find this resource:
Yasuma, F., & Hayano, J. (2004). Respiratory sinus arrhythmia: Why does the heartbeat synchronize with respiratory rhythm? Chest, 125, 683–690.Find this resource:
Yu, Y. H., & Blessing, W. W. (2011). Neurons in amygdala mediate ear pinna vasoconstriction elicited by unconditioned salient stimuli in conscious rabbits. Autonomic Neuroscience, 87, 236–242.Find this resource:


text:
Here is a long overdue testimonial to the untold influence of a gifted Twentieth Century magician's magician, who might well be called "The Father of the Modern Magic Lecture." Among Fetsch's creations is one of the most popular mental magic feats of all time, Mental Epic. Other creations include the popular Rope Epic, Symbologic, and Quad-Ropelets. If this sort of innovative thinking interests you, then Fetsching Magic is a book fit for your library.
The author, Robert Kirkwood Spencer, has spent many years researching the legacy of one of the most prolific creators and inventors in the history of the magical arts. The result is both a tribute biography with many rare photos and an illustrated, detailed instruction book of more than 100 brilliant, unique items of magic and mentalism for close-up and stage. For this magical journey of discovery, there is an introduction by Fetsch's daughter and only child.
Fetsching Magic is a book that will inspire and enthrall you with its special kind of magic for years to come. Readers will be glad to say that they now know "the only and only" Hen Fetsch.
Hard bound, 8.5 x 11", 206 pages.
Do you own this product? Write a review.

subset: commoncrawl


text:
Dennis Chmiel necesitaba un nuevo diseño de logotipo y lanzó un concurso de diseño en 99designs.
Un ganador ha sido elegido entre 38 diseños de 11 diseñadores freelance.
"VLG" http://www.vlg.us
The Veterinary Leadership Group (VLG) is composed of approximately twenty-five current or former veterinary practice owners or senior managers of animal hospitals.
We are a diverse group with many interests and areas of expertise. Represented in the group are both solo and multi-practitioner practices, practices with multiple locations and large referral practices. We have several members who are well recognized in the veterinary world as experts in practice management and marketing, as well as members who are former practice owners but who still contribute as mentors.
The greatest benefit from membership in VLG is the ability to network with a group of individuals and practices regarding any aspect of the business of veterinary medicine. At meetings, we are constantly comparing different methods used to solve similar problems. Between meetings, we use our web site's Discussion Forums to continue these discussions. Additionally, our web site is a repository of documents we can all download for use in our practices.
Our website serves as the introduction for potential new members (managing veterinarians). It also introduces corporate sponsors to our organization who help fund efforts. Our group focuses on management and leadership training with the ultimate goal of promoting high quality veterinary medicine.
We need to update the look of our website but realize that the redesign of our logo must come first, as the website design will be based on the new logo. Our logo appears dated and needs to look vibrant and innovative. Even though this is a veterinary organization, animals are not necessary as part of the logo and the new logo doesn't need to look anything like the current logo (see http://www.vlg.us). We are looking for out-of-the-box ideas.
Descubre cómo funciona un concurso de diseño u obtén más información sobre nuestros servicios de diseño de logo.


text:
It is with pain in my heart that I must say CrypticVPN is shutting down for the forseeable future.
During this shutdown we will be working hard to create a new Windows and Mac client, mobile apps, and getting our payment processing in order. All current and past customers will be welcomed back with a discount in the future.
Thank you for all the support, we would love to see you again sometime!


text:
Move over, John Elway; swimmer Missy Franklin has you beat
John Elway is the king of Colorado sports. And deservedly so. He won two Super Bowls. He embodies Broncomania.
But is Elway the best Colorado athlete of all time? Nope. He has been beaten by an 18-year-old. Swimmer Missy Franklin won six gold medals at the world championships. The only other U.S. swimmers to win at least six golds in a single Olympic or world championship meet? Two guys named Mark Spitz and Michael Phelps. On top of her breakout, stellar performance at the 2012 Summer Olympics, does that put Franklin on a par with Elway? Listen to Peter Burns of Mile High Sports Radio and I debate here:
Who's your nomination for the greatest Colorado athlete of them all? Chauncey Billups? Dave Logan? Somebody else?
Kick it with Kiz and Peter Burns by joining the discussion on Mile High Sports Radio Monday through Friday from 7-9 a.m. At 93.7 FM and 1510 AM.
Find Kiz on Twitter @MarkKiszla. And Peter Burns @PeterBurnsRadio.


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Oct. 13 Bruce Bochy workout day interview
Q. As comebacks go, yours was outstanding. How does the Cardinals coming from six runs down compare to what you guys did by winning three games in Cincinnati?
BRUCE BOCHY: Well, it's impressive what the Cardinals did. And really, if you look at the game we had and the game they had, they were similar. We were up 6 0, barely hung on, and they found a way to get it done. Both clubs at some point had their backs against the wall. We had to win three straight and they're down a couple of runs in the 9th. They found a way to get it done.
I think it says a lot about the two clubs, the character of the clubs and how hard they fight, and it should be a really hard fought series here.
Q. Talk about the logistics, what you guys went through last night. When did you check out of the hotel, when did you leave for the airport, and when did you find out about the results?
BRUCE BOCHY: Yeah, we had, I thought, a pretty good plan (laughter).
We had a little mechanical problem on the plane. But anyway, we watched the first part of the game, the Cardinal/Washington game. And at 11 o'clock we headed to the airport. It was around the 7th inning, and at that time Washington had a lead. So we went through security, got on the plane. And the timing was great. It's the 9th inning and so we could see what was happening and the guys, we're watching the game with a lot of interest. Great game, exciting game.
At one point you think you're heading to Washington and then the Cardinals come back and we realized we were coming home. And then we had a problem on the plane with the hydraulic system. We had to sit there for two and a half hours, and that made it a long night. I think the boys were getting a little restless.
So we got in, I'm not sure what time, 5:30, 6:00, somewhere in there. It was a long night. But we still think we did the right thing on how we headed to the airport at that time. I know the guys would have wanted to come home after the game anyway, instead of staying in Cincinnati. We just got delayed there for a little bit. It worked out fine.
Q. You were on the plane watching the game?
BRUCE BOCHY: Yeah, yeah, yeah. We were all watching the game and could see what was going on. And in a matter of minutes you're going from Washington to coming back home. And it's a great ballgame.
Q. What time did you actually get airborne, do you know?
BRUCE BOCHY: You know, I would say, I don't know, 2:30, somewhere in there. I can't tell you the exact time. At that point I think most of us were asleep or trying to fall asleep. But I know it was two to two and a half hour delay we had.
Q. As a catcher you've seen Buster Posey, 2010, this year, and the inevitable comparisons between him and Yadi Molina are coming up. What are your impressions for somebody that understands it as well as anybody?
BRUCE BOCHY: Well, we saw in 2010 what a difference maker Buster Posey can be for us. And we put a lot on him at that time, at his age, his lack of experience. We put him in the cleanup role and went on to win the World Series because of his bat and how well he caught.
So it shows us not just the talent that Buster has, but his makeup is off the chart in the way he handled everything thrown at him, to be on stage and carry himself the way he did.
And, sure, I think you're talking about two of the best catchers in the game when you're looking at Yadi and Buster, two guys who catch well, throw well, handle the bat, hit for power. They have the whole game. And so it's a big reason why these two teams are here, because of the two catchers. So I'm sure there's going to be a lot of comparisons.
But they're different players. I don't want to go into that. But in their own way, their own style. But both just incredibly talented catchers.
Q. You've announced one and two, is it likely Cain for three, and are you looking for Lincecum as a starter?
BRUCE BOCHY: The reason we named the first two is because we felt we had to. I think you're fair in mentioning Cain likely for Game 3. As far as Game 4, we'll wait to announce that.
Again, we talked about this in the first series. They're all available. The first game or second game here at home and we'll see how it goes and then we'll name Game 4. But Timmy threw the ball great. Zito, he was a little bit off, but not bad. He ended up throwing a lot of pitches. But at this point we're just going to wait until we get to St. Louis before we name those starters.
Q. What has Gregor Blanco meant to the team and to you as a manager as the guy who replaced Cabrera in leftfield?
BRUCE BOCHY: He had a great series against Cincinnati. He had a big home run. Played well defensively. He did a lot of good things. It's not easy to lose a player like a Melky who did a great job for us. But what happened, happened. We crossed that bridge and moved on. And part of the reason we moved on was because of Gregor and the way he played, and Xavier, too, I'll mention. And we couldn't have asked Blanco to do more than what he did in that last series. And he'll be out there in this series. He gives you the added dimension of speed. He also showed he's got some pop. He had a big home run there for us.
It's nice to have a guy like this when you have to replace somebody, you've got a quality outfielder out there who can do some things for you.
Q. What do you have to do to stop what are the key areas that you have to stop the Cardinals to beat them, in your mind?
BRUCE BOCHY: Well, they're a great team, great offensive team. They can beat you in different ways. They have power. They run. They get those timely hits. They won a World Series last year because of being a balanced ballclub that can do a lot of things.
It's not an easy lineup to go through. We know it and you've got to make your pitches or you'll probably pay for it. And they have good pitching and a really good bullpen. They have some guys throwing really hard coming out of that bullpen. And a closer who's throwing well right now.
I said this about the team we just played, Cincinnati, how balanced they are. And you saw how that series went, hard fought series, and I expect the same in this series. You've got to go out and play your best ball. That's the only way you're going to beat a team like this.
Q. How would you assess Bumgarner's start in the Division Series, and what are the qualities about him that give you the confidence to put him in this kind of tone setting Game 1 start?
BRUCE BOCHY: He's done such a great job all year for us in the previous postseason, his first start. He had a good first inning, and he just got out of sync with his delivery and made some mistakes, couldn't get the ball where he wanted and it happened.
But it's a start. And that's how we look at it. These guys are going to have a hiccup now and then. But we still have all the confidence in the world in Madison to go out there and pitch like he's been pitching all year and has thrown well, and hopefully just giving us a chance to win.
Q. Is Zito definitely going to be on the roster for this series?
BRUCE BOCHY: Yeah, Zito will be on the roster.
Q. When you have Lincecum as an option do you play into the Cardinals predominantly right handed hitting, how big a factor is that setting up your rotation?
BRUCE BOCHY: Sure, you've heard me mention all the variables, right handed bats, how they hit righties or lefties, more importantly is how our guys are throwing or playing. And I'm talking about position players.
So we'll look at all those things, how they were used the first two games, who's available. That's why we haven't named Game 3, Game 4 starter. But, sure, I think you have to look at the team that you're playing. For us it's either St. Louis or Washington. It might have made a difference how he ran this rotation out there. But we'll announce that soon.
Q. It's been a few months since George Kontos got called up from the Triple A. What have you seen from him this season, especially in the confidence you've shown in him?
BRUCE BOCHY: I really like the way he's carried himself in the last series. He wasn't afraid. He threw strikes, quality strikes. He really saved us a couple of times going out there and getting some big outs. He hasn't been in this situation before, but you wouldn't know it. That's how you want your pitchers to be, is go out there and throw quality strikes and don't show any fear. And this guy didn't.
And that's why I had no problem putting him in there and he ended up I should say nice surprise. We carried him because we thought he could help us. He ended up being the 11th pitcher, the 12th guy to get some outs.
Q. Of the four teams left to still play and three are managed by former catchers, one, does that prove that catchers are the smartest guys on the field?
BRUCE BOCHY: I don't know.
Q. And two, could Buster and Molina in 15 or 20 years be managers?
BRUCE BOCHY: Yeah, I think they're all catchers. That's a good thing, I think. I've said this, you do see a lot of catchers managing. I do think catchers have a slight advantage as far as making that transition from player to manager because in essence that's what you're doing. You're having to handle a staff, 11 or 12 pitchers. Hopefully you have some understanding of pitching. You're watching the game. You can't drift mentally during the game at all. You've got to keep that focus for nine innings. You're out in the outfield, you can maybe think about that last at bat.
For me being a role player, I watch a lot of games. Hopefully these things help. It doesn't mean managing is going to be for you. But I do think it does help you in making that transition.
You're talking about two guys without question if they wanted to manage, they'd be great managers because of what they do. They're managing a team out there on a daily basis, handling a staff, running the game. You have to know all the signs. You're looking at the manager. There's no part of the game you can't know something about being a catcher. So those two, I think, would be great choices.
Q. Just to clarify, is Lincecum available out of the bullpen in Games 1 and 2?
BRUCE BOCHY: Yes, he is.
Q. Your team has had surges all year long, surges back from difficulties. Is it because of the difficulty that your club rises to the occasion or just in spite of it?
BRUCE BOCHY: No, I think it helps when you've had to go through them. I think it says a lot about the character of a club, I'll start with that, that they have not let anything distract them or cause them to lose any confidence. I'll go back to Spring Training, Sanchez, he ended up going on the DL. Then, of course, Wilson going down. And the Cabrera thing. Every club has to deal with it. It's just not us.
We know all the teams have their ups and downs and have to deal with injuries. But what's important is how you deal with them. This club has kept their focus on winning ballgames. I think once you have to go through them it does help you or have to come back I'll go back to LA, we were behind them, had to go in there and win and these guys did it. And that experience is invaluable. And they did something that's never been done in the National League and that's go in and beat a club on the road, a very good club. And I think it does say a lot about the makeup of the team here.


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U.S. Women's Update - March 2
Bill Kauffman
Manager, Media Relations and Publications
Phone: 719-228-6800
E-Mail: email@example.com
COLORADO SPRINGS, Colo. (March 2, 2009) – The current edition of the U.S. Women's National Team Weekly update released on March 2 includes briefs on national team players competing overseas, U.S. Women's National Team Open Tryouts, trivia questions, how to purchase replica national team jerseys, updated list of United States players competing professionally overseas (including non-National Team members) and much more.
For the complete PDF document that includes the international transfer list, trivia questions and other fan interaction sections, click here.
BERG RINGS STOCK EXCHANGE BELL: Lindsey Berg (Honolulu), a two-time Olympian with the U.S. Women's National Volleyball Team, assisted the Jack Brewer Foundation in ringing the New York Stock Exchange closing bell on Feb. 27. As a Jack Brewer Foundation supporter, Berg assisted in ringing the closing bell along with Foundation founder Jack Brewer, Congressman Charles Rangel and Dallas Cowboy Marion Barber. "This is such a huge honor for me to ring the New York Stock Exchange Bell," Berg said. "Ringing the bell and being a part of the Jack Brewer Foundation is yet another great and positive experience in my life. I am proud to be able to join some other very prestigious people who have had the opportunity to ring the bell. But more importantly, I am happy to be here to support my friend Jack and his foundation. Sometime in the near future, I would like to develop a foundation of my own and become more active in the community." For the full story, click here.
TRIVIA QUESTIONS: 1. How many different U.S. Olympic Teams has Toshi Yoshida been on staff? 2. What former U.S. Olympic National Team player is currently a head coach within the USA Volleyball High Performance Pipeline? Answers can be found on page four in the full PDF version (click here) of the current U.S. Women's National Team Weekly update.
TOM UPDATE: Logan Tom (Salt Lake City, Utah), a three-time U.S. Olympian and Best Scorer of the 2008 Olympic Games, is playing with Hisamitsu Springs in the Japanese V-League. She started the weekend off with 29 points in a hard-fought 19-25, 25-21, 20-25, 25-21, 15-9 victory over Hitachi on Feb. 28. Tom netted 26 kills on 64 attacks, two blocks and an ace in the victory. She added 18 positive service receptions on 29 chances for a 62.1 percent. Tom followed up the performance with 10 points in a sweep (26-24, 27-25, 25-20) over JT on March 1. She was held to just six kills on 24 attacks, but made up on the defensive side of the net with four blocks and an 89.7 positive service reception percent (26 of 29). Hisamitsu Springs moves up to third place in the V-League standings with a 16-8 record and is in good position for the playoffs. Hisamitsu Springs only has a March 8 match next week against Denso, which is currently in fourth place and three victories behind Hisamitsu Springs.
HANEEF-PARK UPDATE: Tayyiba Haneef-Park (Laguna Hills, Calif.), a two-time U.S. Olympian, is competing for the Pioneer Red Wings of the Japanese V-League. She contributed 19 points in a 25-18, 25-22, 25-15 sweep of Hitachi on March 1. Haneef-Park provided 17 kills on 33 attacks with just one error. She added two aces on 13 serves. Pioneer improves to 12-11 on the season and is in sixth place in the V-League standings. Pioneer challenges Takefuji Bamboo (9-12, eighth place) on March 8 in its only match of the week.
METCALF, STALLS UPDATE: Nancy Metcalf (Hull, Iowa), a 2004 Olympian, is playing for Eczacibasi Zentiva of the Turkish professional league along with 2008 Olympic Games alternate Tracy Stalls (Denver, Colo.). Metcalf scored a match-high 16 points as Eczacibasi defeated Nilufer Belediye Spor 25-17, 25-14, 26-24 on Feb. 28. She was credited with 14 kills on 24 attacks, one block and an ace. Stalls chipped in three kills on six swings and two blocks in a starting role. Eczacibasi Zentiva, currently tied for third in the Turkish League with an 11-5 record, returns to action in the CEV Indesit Champions League on March 5 with a Playoff 6 Round match against Poland's Fakro Muszynianka. The home-and-home series concludes on March 11 with a spot into the Indesit Champions League semifinals on the line. To view a photo gallery of Eczacibasi's match against V Gunes Sigorta from Feb. 18, click here.
NNAMANI UPDATE: Ogonna Nnamani (Bloomington, Ill.), a two-time Olympian now playing professionally in Turkey for Galatasaray, tallied 11 points in a 17-25, 25-18, 25-11, 25-22 loss to V Gunes Sigorta on Feb. 25. She recorded nine of her 11 points via kills while adding a block and ace. Galatasaray, currently seventh in the league standings with an 8-7 record, returned to the win column on Feb. 28 as it defeated Konya Eregli 25-23, 25-13, 25-23. Nnamani pounded 17 kills on 28 attempts for a 61 kill percent, while adding four blocks as part of a match-high 21 points.
McGINNIS, HUGHES UPDATE: Angie McGinnis (Fraser, Mich.) and Heather Hughes (Fallbrook, Calif.), both alternates on the 2008 U.S. Olympic Team and now competing for Besiktas JK Bayan of the Turkish professional volleyball league, dropped a 25-14, 19-25, 25-19, 25-21 match to V. Gunes Sigorta on March 1. Full match stats are unavailable. Besiktas is 8-9 on the season and in sixth place.
BUSSE, CRIMES, PRESSEY UPDATE: Toa Baja, competing in the Puerto Rico Super League, features three players who trained with the U.S. Women's National Team during 2008. Cassie Busse (Prior Lake, Minn.), Angie Pressey (Lake Mary, Fla.) and Alexis Crimes (Rancho Cucamonga, Calif.) all are sharing a heavy offensive load for Toa Baja. The trio combined for 35 points as the Llaneras swept Ponce on Feb. 24. Busse and Crimes tallied a dozen points apiece, while Pressey added 11 points and 11 digs. Toa Baja won its 10th match in a row as Busse produced 22 points via 18 kills, two blocks and two aces in a sweep of Mayaguez. Crimes added nine points and Pressey chipped in six points. Jeanne Fairchild led Mayaguez with 12 points in the loss. Toa Baja remained undefeated in 11 matches as it defeated Caguas in straight sets on March 1. Pressey recorded 12 points and 12 digs, while Crimes added 11 points and Busse eight.
OTHER AMERICAN STANDOUTS IN PUERTO RICO LEAGUE: Kylie Atherstone tallied 16 kills in leading Carolina to a sweep of Juncos on Feb. 24. In the loss, Vicky Brown totaled 13 points…Jessica Vander Kooi, in her first match of the season, contributed 13 points with 11 digs and 22 receptions as Mayaguez defeated Guaynabo in four sets. Teammate Jeanne Fairchild added 13 points in the victory, while Lindsay Phillips produced 23 points in the loss…Jane Collymore pocketed a match-high 20 points as San Sebastian defeated Ponce in straight sets on Feb. 26. Kara Uhl, playing her first match for Ponce, tallied 11 points…Vicky Brown chipped in 13 points as Juncos topped Caguas in four sets on Feb. 26. Kelly Wing, playing her first match for Juncos, added nine points, 15 digs and 17 receptions…Jane Collymore charted 20 points and Shonda Cole added 16 points as San Sebastian swept Ponce on Feb. 26. Kara Uhl scored 11 points in the loss…Jordan Larson hammered a match-high 23 points in leading Bayamon to a four-set victory over San Sebastian on Feb. 27. Shonda Cole scored 14 points in the loss, while Jane Collymore added 12…Kristee Porter tallied 16 points in leading Corozal to a sweep of Ponce on Feb. 28…Kylie Atherstone scored a team-high 18 points in leading Carolina to a five-set victory over Mayaguez on March 1. Jessica Vander Kooi was credited with 12 points and 15 digs in the loss…For more highlights from the Puerto Rico Super League, click here.
AH MOW-SANTOS UPDATE: Robyn Ah Mow-Santos (Honolulu), a three-time Olympian for Team USA, has returned to her professional team in Switzerland as Volero continues into the playoffs. In the best-of-five league championship playoff, Volero lost to VC Kanti Schaffhausen 25-19, 25-17, 25-20 in the opening match on the road. "Our organization has to play much better by Wednesday, so we give away fewer points from our own mistakes," Ah Mow-Santos said in a Volero press release. Volero returns home to host VC Kanti Schaffhausen on March 4 as part of the best-of-five series. The third match of the best-of-five is scheduled for March 7. If needed, the final two matches will be played on March 11 and March 14.
SCOTT-ARRUDA UPDATE: Danielle Scott-Arruda (Baton Rouge, La.), a four-time U.S. Olympian middle blocker, tallied eight points for CGF Recycle Florens Castellana Grotte in a 25-23, 25-19, 20-25, 26-24 loss to Monte Schiavo Banca Marche Jesi in an Italian Serie A match on March 1. Scott-Arruda was credited with five kills and three blocks in the match. Castellana Grotte falls to 8-12 on the season and is in ninth place, five points out of reaching eighth place to gain a playoff spot. Castellana Grotte looks to make up ground on March 8 against Yamamay Busto Arsizio, which currently is in sixth place.
BOWN UPDATE: Heather Bown (Yorba Linda, Calif.), a three-time Olympian and middle blocker on the silver-medal winning 2008 U.S. Olympic Team, did not play in her Italian Serie A professional league match on March 1 as Monte Schiavo Banca Marche Jesi defeated CGF Recycle Florens Castellana Grotte 25-23, 25-19, 20-25, 26-24. Jesi improves to 13-7 on the season and remains five points out of third place behind Asystel Volley Novara. Jesi returns to Italian Serie A action on March 7 agaist Riso Scotti Pavia. Jesi will also host the GM Capital Challenge Cup on March 14-15 as it plays Leningradka in the semifinals.
WILLOUGHBY UPDATE: Kim Willoughby (Napoleonville, La.), a 2008 U.S. Olympic Games silver medalist and now playing for Despar Perugia in the Italian Serie A league, played a limited role in her team's five-set loss to Famila Chieri on March 1. Willoughby entered as a sub in the third set and started the fourth set, which resulted in Perugia winning both 25-23, 25-22 to tie the match and send it to the tiebreaker. However, Willoughby was not on the court in the 15-8 tiebreaker loss. She scored one kill on five attempts in the match. Perugia, 11-9, is in fifth place in the Italian Serie A standings. Perugia takes on Asystel Volley Novara on March 8 in its next match.
GLASS UPDATE: Kim Glass (Lancaster, Pa.), a 2008 U.S. Olympian playing professionally in Russia with Universitet Belogorie, did not play in her team's 25-23, 25-20, 25-18 loss to Zarechie-Odintsovo on March 1. Universitet Belogorie returns to action on March 8 against league-leader Dinamo.
JOINES, RICHARDS UPDATE: Jennifer Joines (Milpitas, Calif.), a 2008 U.S. Olympian, and Kristin Richards (Orem, Utah), a 2008 U.S. Olympic Team alternate, are competing for Fakel in the Russian professional league this winter. Fakel dropped a heart-breaking five-set match to Avtodor-Metar on Feb. 28. Match statistics were not available for the match when this release was distributed. Fakel faces Spartak on March 8.
OLYMPIC LIBEROS TO HOST CAMP:www.finerpointsvball.com.
2009 PAN AMERICAN CUP COMING TO MIAMI: USA Volleyball will host the Eighth Annual Women's Pan American Cup June 26-July 4 in conjunction with the USA Junior Olympic Girls' Volleyball Championship in the Miami area. The nine-day Pan American Cup, which will tentatively have three of the four 2008 Olympic Games semifinalists (Brazil, USA and Cuba), will be played on the campuses of the University of Miami and Florida International University. "USA Volleyball is extremely excited about the opportunity to host one of the largest international volleyball events in Miami and to pair it with the 2009 USA Junior Olympic Girls' Volleyball Championships," USA Volleyball Chief Executive Officer Doug Beal said. "It will provide a unique opportunity for our developing young volleyball players to be exposed to elite international volleyball teams from North America, South America and the Caribbean. The two events will also generate terrific excitement in the community and lead to greater popularity for the sport." USA Volleyball is hosting its first-ever Women's Pan American Cup, which serves as a qualifying event into the 2010 FIVB World Grand Prix. The event is the largest international volleyball event hosted by USA Volleyball in terms of country participation. Team USA has not hosted a women's senior-level international tournament since the 1998 FIVB World Championship Qualifier tournament in 1998. Due to international scheduling and professional league commitments, matches on domestic soil have become a rarity with only seven contests against foreign teams in the most recent Olympic quadrennial (2005-2008).
REPLICA JERSEY AVAILABLE FOR LIMITED TIME: Are you looking for a unique holiday gift for your volleyball loved ones? USA Volleyball has the answer with replica jerseys from its 2008 Olympic Games indoor teams being made available for a limited time by clicking here. The U.S. Olympic Women's Team replica jerseys, priced at $65 apiece, are available in extra small, small, medium, large and extra large. Replica jerseys are available for all 12 U.S. players who participated in the 2008 Olympic Games. Each replica jersey will have the Olympian's name on the back with their jersey number on both the front and back. In addition, USA Volleyball has several other 2008 Olympic Games apparel items commemorating the unprecedented indoor and beach volleyball success obtained in Beijing. Products available on the online store include short and long-sleeve T-shirts, sweatshirts and hoodies in multiple designs.
OLYMPIC COMMEMORATIVE APPRAREL ON SALE: USA Volleyball has unveiled five commemorative logo designs to appear on apparel saluting USA Volleyball's medal successes at the recent Olympic Games and Paralympic Games in Beijing. Apparel can be purchased by clicking here. Men's and ladies' T-shirt designs are $15, while the youth T-shirt size is $13. Long sleeve t-shirts are $18, crew sweatshirts are $23 and hoodies are $30. Sizes XXL and larger have a slightly higher price. USA Volleyball's success on the Olympic grand stage in Beijing has never been achieved by any other nation since volleyball was added to the Olympics in 1964. The U.S. Olympic Men's Indoor Volleyball Team, which was named the United States Olympic Committee Team of the Month for August 2008, captured the gold medal at the Olympic Games without losing a single match. Women's Beach Volleyball (Misty May-Treanor and Kerri Walsh) and Men's Beach Volleyball (Phil Dalhausser and Todd Rogers) both came back from Beijing with Olympic Games gold medals. The U.S. Olympic Women's Indoor Volleyball Team captured the silver medal in Beijing, as did the U.S. Women's Sitting Team during the Paralympic Games. No other country has ever participated in the gold-medal match of all four Olympic Games volleyball disciplines during the same year. Team USA added a fifth gold-medal appearance at the Paralympic Games.


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Granted, this sign at tonight's Mississippi State/LSU game would have been more phenomenally noteworthy had a prominent "O" been an afterthought to a prominent "U," but it's phenomenal in and of itself. Several tipsters are to be commended for sending this in. You know who you are.
The No. 3 and No. 25 teams in the land are tied at three in the second quarter.


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1 SalaryUpdated Sep 6, 2016
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It is late Tuesday night and I am sure all of you are preoccupied with your Hechos de Pesach or Passover Preparations. I have lost count of how many grocery stores and how many dozen eggs I have purchased. I will share something with you all, [click to continue…]
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- Description
- Tasting Notes
- What's Inside
- Occasions
Convey an unforgettable message of love, friendship, and appreciation with the stunning gift of eighteen fresh pink roses dramatically arranged with lush ivy.
The 60 cm roses are artistically arranged with garden greens to create a large and eye-catching display. When hand-delivered to the recipient's door, this classic bouquet always fills the recipient's heart with joy and amazement.
Gift Includes:
- 18 Pink Long-Stemmed Roses (60 cm).
- Green Ivy.
- Pitta Negra.
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- A plush teddy bear, balloons, wine, champagne, or chocolates may be added to your order based on availability. Please contact customer service for more information.
Measures approximately 20" x 28".
During checkout, please be sure to indicate your preferred occasion when you choose a gift card. Exact flowers and vase may vary depending upon location and availability.
Same day delivery is available if you place your order by 2pm in your recipient's time zone, M-F and by 1pm on Saturday. To see if Sunday delivery is available in your area please contact customer service.Gift #13147
Dreaming in Pink Rose Bouquet is a hand delivered gift. These gifts are delivered by one of our local design centers located throughout the United States and Canada.
Typically, standard deliveries are made between 9:00 AM and 6:00 PM, with business deliveries before 5:00 PM. Hours may be extended during holidays. Please note in some locations we may need an additional 24 hours for the delivery of exotic flowers, wine and fruit baskets.
Same day delivery is available for most gifts when ordered before the cutoff time. Saturday delivery is possible if ordered before 12 PM Friday. The cutoff time for Dreaming in Pink Rose Bouquet is in the recipient's time zone.
Dreaming in Pink Rose Bouquet has been purchased most frequently by our customers for the following occasions:
Average Rating:(4 reviews) write a review
MaddieGot there before she went to workMay 28, 2017
I ordered the best 30 roses about 3 days before my aunt's birthday I paid for the extra shipping cost ( guaranteed to arrive before 2pm ) and put a note asking if they can be delivered before 12pm because my aunt has work at 12; they were delivered around 10am which was perfect timing! I'm super happy she got her flowers on her birthday before she went to work and she was super impressed by the arrangement.
XfactorEcstatic WifeMay 13, 2015
My wife really enjoyed the flowers and vase. They were a bit pricey but anything for her. The delivery was also as promised. This was so many flowers and so much greenery that the base of the vase was really too small. It was quite nice but a vase with a larger base for this arrangement would definitely help for its stability.
Amazing presentation, courteous delivery person, just as ordered.
Mclark1990Huge roses...May 12, 2014
I ordered these for a friend who recently lost her mother. Her mother loved pink roses. I was told that these were the most beautiful arrangement of roses that she had ever seen. She sent me pictures via text to show how truly pink the roses were and commented for several days on the size of each flower.


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Welcome to WestportKC.com
Westport is one of Kansas City's premier destinations for dining, shopping, site seeing and is the heart of the city's nightlife. Located in the midtown, Westport is just North of the Country Club Plaza and a few miles South of downtown Kansas City.
Before there was a Kansas City, there was a Westport, built along the Santa Fe Trail as an outfitting center for wagon trains heading west. Today the area is filled with renovated and new buildings housing trendy shops, restaurants, and nightspots. Read more about the history of Westport.