The effects of milrinone in the neonatal pig heart

Summary

Milrinone, a selective inhibitor of phosphodiesterase (PDE), was examined in neonatal hearts and in ventricular myocytes. Isolated, paced (180 beats/min), isovolumically beating hearts from pigs, <3 days of age, were perfused with an erythrocyte-enriched solution. In one group (control, n=6), milrinone was studied at perfusate concentrations of 1, 10, and 100 μg/ml. In a second group (postischemia, n=10), hearts were subjected to 30 minutes of no-flow ischemic arrest, prior to the addition of milrinone. Left ventricular peak systolic pressure (PSP) and end-diastolic pressure, coronary flow (CF), heart rate (HR), and myocardial oxygen consumption (MVO₂) were measured. The PSP averaged ∼100 mmHg during the baseline periods for both groups and decreased to ∼85 mmHg in those hearts subjected to ischemic arrest. In both groups, PSP increased ∼14% at the 1μg/ml concentration of milrinone. No additional increases in PSP were observed in the control group at the higher concentrations. However, PSP increased 28% and 41% (p<0.05), in the postischemia group at the 10 and 100 μg/ml concentrations, respectively. The CF averaged ∼3 ml/min/g during the baseline periods of both groups and increased significantly at each milrinone concentration. The HR in both groups increased to ∼200 and ∼250 beats/min at the 10 and 100 μg/ml concentrations, respectively. Additionally, milrinone's effects in intact hearts were found to be comparable to those of isobutylmethyl xanthine (IBMX), a nonspecific PDE inhibitor. In isolated myocytes, however, milrinone produced only modest increases in cAMP levels, compared to IBMX. We conclude that milrinone has positive inotropic, coronary vasodilatory, and chronotropic effects in the neonatal pig heart. In particular, milrinone also was capable of reversing the contractile dysfunction that resulted when these immature hearts were subjected to 30 minutes of normothermic, no-flow ischemic arrest. Thus, milrinone may be a useful agent in the treatment of neonates with contractile dysfunction.