Developmental changes in reperfusion injury. Comparison of intracellular ion accumulation in ischemic and...

Developmental differences in ischemic and potassium cardioplegic arrest were evaluated in newborn (birth to 7 day old) and adult (6 to 12 month old) New Zealand white rabbit hearts isolated and perfused by Langendorff's method. An extracellular space washout technique was used to measure intracellular sodium and calcium in the two age groups after ischemia alone, after normothermic and hypothermic cardioplegia, and after cardioplegia with reperfusion. Although the intracellular ionic contents of nonreperfused adult hearts after 30 and 40 minutes of ischemia were identical, there was a twofold elevation in intracellular sodium level after 40 minutes of ischemia in the newborn hearts. Adult hearts arrested by normothermic potassium cardioplegia demonstrated no alteration in the intracellular ionic content, whereas in the newborn hearts, potassium cardioplegia produced excess intracellular calcium loading before reperfusion, which was greater than that occurring with ischemia alone. When hypothermia (12 degrees C) was combined with cardioplegic arrest, a prereperfusion influx of sodium and calcium was not observed in the newborn hearts, and ionic reperfusion injury was blunted in both newborn and adult hearts. These studies demonstrate that the newborn heart is more susceptible than the adult to both ischemia and cardioplegia. This may be due to age-dependent differences in transmembrane passive diffusion, sodium/calcium exchange, or calcium slow channel properties and suggests alternative myocardial protective strategies for the newborn infant.