Repletion of high energy phosphates in the postischemic neonatal heart

Milrinone improves function in failing adult hearts, but it has not been examined in the immature myocardium. The purpose of this study was to characterize the effects of milrinone, a phosphodiesterase inhibitor, on immature hearts, and compare these to dobutamine, a commonly used catecholamine inotrope. One hundred isolated working neonatal rabbit hearts were used. Hearts were made ischemic (37 degrees C) for 1 hour and reperfused for 0, 10, 40, or 70 minutes. In separate groups, infusion of milrinone (1.0 microg/mL) or dobutamine (0.1 microg/mL) was begun after reperfusion for 10 or 40 minutes. High energy phosphates, total nondiffusable nucleotides, cyclic adenosine monophosphate (cAMP), and the percent recovery of cardiac output were determined. Cardiac output returned to normal, and adenosine triphosphate (ATP) and total nondiffusable nucleotide levels did not decline when dobutamine or milrinone were begun after 10 minutes of reperfusion. In hearts receiving inotropes after 40 minutes of reperfusion, when high energy phosphates were low, ATP increased, and total nondiffusable nucleotide repletion was observed. Cardiac output did not improve when inotropes were begun after 40 minutes. cAMP was higher in milrinone hearts compared to dobutamine, but there was no simple relation between cAMP and ventricular function. Inotropes may increase purine salvage pathway activity. Deriving maximum benefit from inotropes may depend on beginning infusions early, before the appearance of irreversible changes.