PHARMACOLOGICAL SUPPORT WITH HIGH-ENERGY PHOSPHATE PRESERVATION IN THE POSTISCHEMIC NEONATAL HEART

Milrinone improves function in failing adult hearts. This study examin ed its effect on immature myocardium, Using an isolated working neonat al rabbit heart preparation, we measured myocardial function, high-ene rgy compounds, and cyclic adenosine monophosphate. Hearts were subject ed to 1 hour of normothermic ischemia, 10 minutes of reperfusion with Ringer's solution, and 30 minutes of reperfusion with either unaltered Ringer's, Ringer's with dobutamine (0.1 mu g/mL), or Ringer's with mi lrinone (1 mu g/mL). These hearts were compared with each other, with a control group continuously perfused for 70 minutes, and with a group of hearts that were made ischemic and reperfused for only 10 minutes. There was a progressive decline in adenosine triphosphate levels meas ured in hearts from the groups receiving 10 and 40 minutes of reperfus ion with unaltered perfusate, and cardiac output fell to 82% + 4% of p reischemic control in the latter group. When either dobutamine or milr inone was added to the reperfusion solution, postischemic myocardial f unction was restored completely, and the loss of adenosine triphosphat e with reperfusion was halted. Cyclic adenosine monophosphate level wa s highest in ischemic/40-minute reperfused hearts, and there was no me asurable increase in cyclic adenosine monophosphate level in the group of hearts receiving milrinone. The mechanism of preservation of high- energy stores with inotropic agents is not known but may involve poten tiation of mitochondrial oxidative phosphorylation. Beginning presser support early in the reperfusion period may help preserve adenosine tr iphosphate, and use of milrinone may be an important new adjunct in th e treatment of neonates with myocardial dysfunction after congenital c ardiac operations.