This application proposes to develop improved methods of myocardial preservation during cardiac surgery and to define mechanisms through which the heart may tolerate prolonged cardioplegic (CP) arrest. 1) On-line measurements of myocardial pH during infusion of oxygenated versus aerated hypothermic (H) CP solutions will be correlated with myocaridal preservation in dogs. Preservation will be assessed by left ventricular function curves (right heart bypass) and by myocardial biopsies for purine content, including creatine phosphate, ATP, ADP, AMP, adenosine, inosine, hypoxanthine, and xanthine (high pressure liquid chromatography), water content, and ultrastructure (electron microscopy). Adequacy of 02 delivery during arrest and recovery will be assessed from myocardial oxygen consumption, tissue PO2 and PCO2 (mass spectrometer), and regional myocardial blood flow (microspheres). 2) Measurements in isolated rate hearts of pH, ATP, and creatine phosphate with 31P nuclear magnetic resonance will characterize further the beneficial effects of oxygenation of HCP solutions. Basic studies of the effects of temperature alone on intracellular pH will also be done in the same model. 3) The effects on myocardial preservation of adding substrates for aerobic and anaerobic metabolism and for purine synthesis and salvage to oxygenated HCP will be measured in dogs. Substrates studied will be glucose, pyruvate, glutamate, adenosine, inosine, hypoxanthine, and ribose. Measurements of preservation and function will be as in Part 1) above. 4) In the isolate, hypothermic, arrested canine heart the supply, uptake, and consumption of 02 will be elucidated. O2 consumption during adequate O2 supply will be related to myocardial temperature. Effluent perfusate PO2, and myocardial PO2, pH, water, and coronary vascular resistance will be related to O2 consumption during progressive hypoxia. An intermittent perfusion schedule, with perfusion duration, volume, and interval optimized, will be designed from determinations in the heart at 10 C (a level of hypothermia attained clinically) of the time course of O2 uptake, and ability to repay O2 debt and reverse ischemic effects. Duration of stability at 10 C during perfusion with this schedule will be assessed from myocardinal O2 consumption, PO2, pH, water, purine content, and ultrastructure. How O2 uptake during a brief perfusion is divided between temporary cardiac O2 stores and immediate consumption will be determined by comparing uptake before and during cyanide inhibition of cellular respiration. Whether a few red cells, independent of O2 carriage, added to oxygenated crystalloid cardioplegia can increase O2 consumption and extraction will be tested. In view of the more than 200,000 open heart surgical procedures performed each year in the United States, optimum intraoperative myocardial preservation is of major importance to health care.
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| Horvath, K A; Torchiana, D F; Daggett, W M et al. (1992) Monitoring myocardial reperfusion injury with NADH fluorometry. Lasers Surg Med 12:2-6 |
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