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Regulation of Cardiac Output with Controlled Heart Rate in Newborn Lambs

ABSTRACT: To determine the factors regulating cardiac output in newborn lambs and to examine the effects of age after birth, we altered heart rate, afterload, preload, and myocardial contractility in eight younger lambs, 5 to 13 days old, and seven older lambs, 15 to 36 days old. To control heart rate, we ablated the atrioventricular node by injecting formalin into the region of the node, and paced the right ventricle at a baseline heart rate of 200 beats/min. After the lambs recovered from surgery, we performed two protocols. In the first protocol we assessed the effects of changing heart rate by pacing the ventricle at various rates. We also examined the effect of altering afterload and preload at a fixed heart rate: afterload was increased by infusing phenylephrine and decreased by infusing nitroprusside. Preload was increased by infusing blood or 0.9% NaCl solution over 2 min. In the second protocol, we increased myocardial contractility by infusing isoproterenol at a fixed heart rate. Increasing heart rate above baseline levels caused no significant increase in cardiac output in the younger lambs (3.9 ± 4.0%, mean ± SD), and only small increases in the older lambs (11.4 ± 6.7%). Decreasing heart rate, however, resulted in a progressive decrease in cardiac output in both groups of lambs. Decreasing afterload caused no significant increase in cardiac output in the younger lambs (1.4 ± 14.0%) and only a small increase in the older Iambs (11.1 ± 1.9%). However, increasing afterload resulted in a fall in cardiac output in both groups of lambs, but this was significant only in the younger group (-14.4 ± 8.2%). Volume infusion caused a modest increase in cardiac output in the younger lambs (19.9 ± 13.8%) and a more variable but not significant response in the older lambs (15.8 ± 18.2%). Isoproterenol infusion caused the largest increases in cardiac output of 33.5 ± 10.8% in the younger lambs and 64.0 ± 20.0% in the older lambs at a dose of 0.3 μg/kg/min. We conclude that 1) resting heart rates are near optimal in lambs such that increasing heart rate by ventricular pacing does not markedly increase cardiac output, whereas decreasing heart rate significantly decreases output; 2) afterload is near optimal as well since decreasing afterload minimally increases cardiac output, whereas increasing it markedly reduces output; 3) the response to volume loading is limited in the lamb during ventricular pacing; and 4) there is a significant response to β-adrenoreceptor stimulation with out changes in heart rate, and this response is more pronounced in the older lamb. This supports the concept that there is a postnatal change in β-adrenoreceptor stimulation of myocardial performance.