Bipyridine derivatives lower arteriolar resistance and improve left ventricular function in newborn lambs

Milrinone may be used in the treatment of pulmonary hypertensive diseases of the newborn. We have studied its effects in chronically instrumented newborn lambs over a dose range from 1-100 micrograms/kg. These actions have been compared with those of amrinone. We have also tested the effect of milrinone on hypoxia and leukotriene D4-induced pulmonary vasoconstriction. Injected into the right pulmonary artery, both amrinone and milrinone cause a dose-related fall in pulmonary arteriolar resistance with milrinone being approximately 20 times more potent than amrinone and possessing an ED50 of about 10 micrograms/kg. Both agents increase left ventricular dp/dt significantly and tend to increase cardiac output. Systemic vascular resistance falls with both drugs but the change is significant only with milrinone. While milrinone attenuates the increase in pulmonary arteriolar resistance induced by leukotriene D4 and hypoxia, this is probably an indirect effect. Milrinone does not modify either the increases in left atrial, aortic pressure, and systemic vascular resistance or the decreases in cardiac output and left ventricular dp/dt induced by leukotriene D4. These findings suggest that milrinone deserves clinical trial in newborn infants with pulmonary hypertension in whom myocardial depression often coexists.