Age differences in effects of hypothermic ischemia on endothelial and ventricular function

Abstract

Prior studies indicate that immature myocardium has a greater tolerance to ischemia. Prior studies from our laboratory have shown that impaired postischemic endothelial function was correlated with reduced ventricular contractility, and that coronary endothelium has an important role in ischemia and reperfusion injury in neonatal hearts. We examined the differences of endothelial function as well as ventricular function between immature and mature hearts in isolated blood-perfused lamb and sheep hearts after 2 hours of 15 degrees C cardioplegic ischemia. Three groups were defined according to age: neonatal ( < 1 week) hearts (n = 8), infant (1 month) hearts (n = 8), and adult (1 year) hearts (n = 6). Each of the three groups underwent a similar protocol including ischemic time, myocardial temperature, and cardioplegic solution. Based on earlier work, all had low perfusion pressures during the first 10 minutes of reperfusion. Thereafter the perfusion pressure was constant at 60 mm Hg in the neonatal hearts, 80 mm Hg in the infant hearts, and 100 mm Hg in the adult hearts to match the mean arterial pressure at each age in this species. At 30 minutes of reperfusion, the neonatal and infant hearts achieved significantly improved recovery of left ventricular systolic (maximum developed pressure and positive first time derivative of pressure, and volume normalized developed pressure and first time derivative of pressure) and diastolic (negative maximum first time derivative of pressure) functions and coronary blood flow. The postischemic endothelial function determined by the coronary vasodilator response to acetytlcholine was better in the neonatal and infant hearts compared with the adult hearts (p < 0.05). These results show that the immature hearts had better recovery of endothelial function and coronary blood flow as well as ventricular function compared with adult hearts after hypothermic ischemia and reperfusion. These results combined with previous studies add further support to the concept that events in the coronary vascular bed play an important role in reperfusion injury in both immature and mature hearts.