The long-term goal of this research is to evaluate alternative methods of myocardial preservation and to assess the significance of risk factors such as hypoxemia or age in children who must undergo cardiopulmonary bypass. Three hypotheses will be tested in an animal model: (1) The presence of chronic hypoxemia prior to global ischemia and reperfusion (GIR) is associated with more severe cardiac deficits after GIR than is seen in hearts from normoxic animals; (2) The administration of an oxygen free radical scavenging solution (ORS) prior to GIR improves the subsequent cardiac status compared to potassium-containing (KCS) cardioplegic solutions or control (NaCl); (3) The neonatal heart suffers more severe damage from GIR than does the adult heart. Hearts from 4 groups of neonatal (10 day old) and adult (8 weeks old) New Zealand white rabbits, raised under normoxic or hypoxic conditions will be studied in an isolated heart apparatus. Following control electrophysiological (E) and ventricular function (F) measurements, the hearts will alternatively receive NaCl, ORS, or KCS prior to 60 minutes of hypothermic (15 degrees C) ischemia. The initial studies will be repeated after 5 minutes and 45 minutes of reperfusion (E) or at 45 minutes after reperfusion (F). Tissue will then be collected for cellular E studies, papillary muscle contractile measurements, histopathology including electron microscopy, and wet weight/dry weight determination. Hearts from an additional control group of normoxic 10 day old rabbits will undergo similar E and F measurements. However, these hearts will be maintained at normal perfusion conditions for 1 hr. 45 min, with subsequent E, F, and other studies conducted as already described. These studies will test the stated hypotheses and provide a data base for future development of methods of myocardial preservation in the infant.
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