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Effects of Vasoactive Drugs on Thromboxane A2 Mimetic-Induced Pulmonary Hypertension in Newborn Lambs

ABSTRACT: Isoproterenol, dobutamine, dopamine, and nitroprusside are four vasoactive drugs used to decrease pulmonary arterial pressure and increase cardiac output in newborns, infants, and children with sepsis. Thromboxane A2 likely produces some of the hemodynamic changes in sepsis, and U46619, a thromboxane A2 mimetic, produces similar changes in lambs. We studied the hemodynamic effects of these four vasoactive drugs in 10 spontaneously breathing newborn lambs during an infusion of U46619. After baseline hemodynamic measurements, U46619 (1–2 μg/kg/min) was infused to increase pulmonary arterial pressure and to decrease cardiac output. Then, either isoproterenol (0.05–1.0 μg/kg/min), dobutamine (5–20 μg/kg/min), dopamine (3–30 μg/kg/min), or nitroprusside (0.5–10.0 μg/kg/min) was infused. Every 10 min, measurements were repeated and the dose increased. U46619 significantly increased pulmonary arterial pressure by 182% and decreased cardiac output by 25% (p < 0.05). Isoproterenol decreased pulmonary arterial pressure by 30% (p < 0.05) and increased cardiac output by 25% (p < 0.05) at low doses, and increased cardiac output by 115% at the maximum dose (p < 0.05). Dobutamine decreased pulmonary arterial pressure by 11% (p < 0.05) and increased cardiac output by 28% (p < 0.05) at low doses, and increased cardiac output by 71% at the maximum dose (p < 0.05). Dopamine did not decrease pulmonary arterial pressure or increase cardiac output. Nitroprusside decreased pulmonary arterial pressure by 11% at the maximum dose (p < 0.05). Isoproterenol and dobutamine may be more useful than dopamine and nitroprusside in the management of pulmonary hypertension and decreased cardiac output during sepsis.