ENERGY METABOLISM IN THE IMMATURE HEART

我们建议测试的假设，在代谢的差异， 成熟期ATP合成、运输和利用的调节机制 和未成熟心肌是其潜在的重要组成部分， 对缺氧、缺血和再灌注的敏感性差异 受伤 这些差异可能会产生独特的要求， 停搏液对未成熟心肌的保护作用。 由于组织 在正常情况下，调节ATP含量变化的酶的含量 和肥大性生长，我们将研究心肌在不同阶段， 成熟，有和没有肥大。 将采取两种办法。 首先，我们将利用我们独特的机会， 来自新生儿和婴儿心肌的材料， 没有心脏病的捐赠者和患有心脏病的捐赠者 手术 其次，建立正常兔心脏模型， 肥大性生长伴或不伴发绀;明确组织变化 参与ATP代谢的某些蛋白质的含量;然后，使用 P-31核磁共振磁化转移技术，评估这些影响 缺氧前后心脏不停跳ATP周转的变化 和局部缺血。 在确定了不同的敏感性之间的任何差异， 成熟和未成熟心肌对缺氧、缺血和再灌注的影响 我们将开发新的心脏停搏策略，以保护 不成熟的心脏 我们的主要目标是实现最佳保护 在缺血/心脏停搏期间的未成熟心肌， 早期再灌注。

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.