Age-related differences in myocardial metabolism affects response to ischemia. Age in heart tolerance to ischemia

Abstract

Difficulties persist in providing optimum myocardial protection to neonatal hearts undergoing congenital cardiac repair. Controversy on actual ischemic sensitivity of neonatal hearts compared to adult hearts may depend on species, age selected, and conditions of the experimental protocol. In 1985, our laboratory began to investigate this area using the time to ischemic contracture (TIC) model popularized by Hearse and Wechsler and reported that neonates developed TIC in a significantly shorter time than adult hearts. The neonatal heart had rapid lactate accumulation and early rapid decline in glycogen that was not sustained. This led to ATP decline and triggered TIC. The adult heart had a more gradual lactate accumulation with complete glycogen utilization. As a result ATP stores were maintained longer, which prolonged TIC. Neonatal hearts demonstrated sensitivity to alterations in extracellular calcium and only minimal additional detrimental effects of ventricular fibrillation (VF) on TIC. More complete glycogen utilization and a greater tolerance to ischemia was noted in the neonates when constant washout was provided by removing tissue metabolites (Lactate). In neonates moderate hypothermia (25 degrees C) and deep hypothermia of varying levels (19 degrees C, 12 degrees C) demonstrated that lactate accumulation was significantly less than normothermia and ATP decline was slowed. A subgroup of hearts had 40%-50% lower ATP stores before ischemia and significantly shorter TIC. These "at risk" hearts do not have the same safe time for surgical repair. Further developments will result in improved outcomes for this young patient population.