Decrease in acute myocardial ischemia by hyaluronidase in isolated, perfused, rabbit hearts

Abstract

Hyaluronidase has been reported to reduce infarct size and cellular damage after coronary artery occlusion. The influence of hyaluronidase (H) on experimental myocardial ischemia was studied in isolated perfused rabbit hearts. Changes in ischemic area were assessed by epicardial NADH fluorescence photography, an intrinsic, high-resolution display of myocardial ischemia. Computerized determination of ischemic area was made from standardized photographs. H was begun 5 min after coronary artery ligation at 4 units/ml perfusate. NADH fluorophotographs were taken at 10-min intervals up to 40 min of ischemia. Coronary sinus oxygen tension ( P esO 2) myocardial oxygen consumption (MV̇ O 2) and coronary flow were determined. After 40 min, the hearts were perfused with a rhodamine solution to indicate areas of myocardial perfusion. In 18 H-treated hearts 55 ± 6% (mean ± SE) of the nonperfused area was ischemic (NADH fluorescent) and the ischemic areas had a patchy distribution. In 26 untreated hearts 86 ± 2% of the nonperfused area was ischemic and the ischemic areas were uniform, ( P < 0.001). The distance between perfused and ischemic tissue was 861 ± 76 μm in the H-treated and 359 ± 19 μm in the untreated hearts, ( P < 0.001). In the H-treated hearts P esO 2 increased to 154% of the postligation control while it decresed to 77% in the untreated hearts ( P < 0.001). MV̇ O 2 decreased to 87% of control after ligation in both groups. The H-treated hearts had a further decline of 37% while the untreated hearts had no further change. In the H-treated hearts, coronary flow increased to 150% of the postligation control while it fell to 80% in the untreated group ( P < 0.001). We conclude that hyaluronidase increases P esO 2 and coronary flow while it decreases MV̇ O 2 during acute ischemia. In hyaluronidase-treated hearts, significant amounts of myocardium remain normoxic within the nonperfused areas.