We propose to test the hypothesis that differences in the metabolic machinery regulating ATP synthesis, transport and utilization in the mature and immature myocardium are important components underlying their differences in susceptibility to hypoxic, ischemic and reperfusion injuries. These differences may create unique requirements for adequate cardioplegic protection in the immature myocardium. Since the tissue content of those enzymes which regulate ATP content changes during normal and hypertrophic growth, we will study myocardium at different stages of maturation, with and without hypertrophy. Two approaches will be adopted. First, we will take advantage of our unique opportunity to analyze biopsy material from the myocardium of neonates and infants, both from organ donors with no heart disease and from those with disease undergoing surgery. Second, we will establish rabbit heart models of normal and hypertrophic growth with and without cyanosis; define changes in the tissue content of certain proteins involved in ATP metabolism; and then, using P-31 NMR magnetization transfer techniques, assess the impact of these changes on ATP turnover in the intact beating heart pre- and post-hypoxia and ischemia. Having defined any differences between the susceptibility of the mature and immature myocardium to hypoxic, ischemic and reperfusion injuries, we will then develop new cardioplegic strategies to protect the immature heart. Our major goal is to achieve optimal protection of the immature myocardium during both ischemic/cardioplegic arrest and also during early reperfusion.
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