STUDIES OF CONTROLLED REPERFUSION AFTER ISCHEMIA: XI. Reperfusate composition: Interaction of marked hyperglycemia and marked hyperosmolarity in allowing immediate contractile recovery after four hours of regional ischemia

Abstract

This study tests the hypothesis that improved muscle salvage after prolonged ischemia (4 hours) occurs when the substrate-enriched blood cardioplegic solution is markedly hyperglycemic (greater than 400 mg/dl) and markedly hyperosmotic (greater than 400 mOsm). Thirty-five dogs underwent 4 hours of occlusion of the left anterior descending coronary artery and reperfusion during total vented bypass with substrate-enriched blood cardioplegic solution, in which the glucose concentration and osmolarity were varied in relation to one another. Spontaneous systolic shortening recovered consistently (31 +/- 6%) only when glucose was greater than 400 mg/dl and osmolarity was greater than 400 mOsm. The least recovery occurred (only one of six dogs recovering spontaneous shortening) when cardioplegic glucose was greater than 400 mg/dl and osmolarity was greater than 400 mOsm. Regional segments reperfused with our standard substrate-enriched blood cardioplegic solution had lower transmural flow rates following reperfusion (56 versus 87 ml/100 gm/min, p less than 0.05), markedly reduced mitochondrial State 3 and State 4 respiration in epicardial and endocardial muscle (p less than 0.05), and the most extensive histochemical evidence of damage (63% area of nonstaining versus area at risk, p less than 0.05). We conclude that markedly increased levels of osmolarity (greater than 400 mOsm) and glucose (greater than 400 mg/dl) improve the capacity of substrate-enriched blood cardioplegic solution to salvage myocardium after prolonged ischemia.