Effect of hyaluronidase during the early phase of acute myocardial ischemia: An ultrastructural and morphometric analysis

Abstract

Hyaluronidase has been shown to reduce the size of experimental myocardial infarcts and to prevent the reduction in collateral coronary blood flow that normally occurs 15 minutes to 6 hours after coronary occlusion. To study the mechanism of action of this agent further, its effects on cardiac ultrastructure during the early phases of myocardial ischemia in the rat were examined. The left coronary artery was ligated for 1 or 3 hours in untreated and hyaluronidase-treated rats and tissue was sampled for electron microscopy. Morphometric analysis, using light microscopy on 1 μ thick specimens of tissue taken from comparable anatomic sites of the ischemic anterior left ventricular wall 3 hours after occlusion, showed that in the untreated rats 80 ± 7 percent (mean ± standard error) of myocardial cells and 48 ± 8 percent of vessels had morphologic evidence of ischemic damage, whereas in treated rats 50 ± 10 percent of myocardial cells ( P < 0.05) and 24 ± 6 percent ( P < 0.05) of vessels had ischemic changes. Ultrastructural studies of untreated ischemic tissue at 1 hour showed absence of glycogen, nuclear chromatin clumping, intermyofibrillar edema, I bands, intramitochondrial dense bodies and edema, endothelial blebs, gaps and swelling and decreased pinocytotic vesicles, red cell sludging and microscopic foci of hemorrhage. At 3 hours myocardial cell and vascular damage were more severe. In treated animals, more myocardial and endothelial cells from the ischemic anterior ventricular wall appeared normal on electron microscopy at both times. In these animals, myocardial cells that showed ischemic damage had nuclear, mitochondrial and myofibrillar morphologic features similar to those of untreated rats, but more glycogen granules were present than in the untreated group. Hyaluronidase may protect ischemic myocardium by preserving glycogen, and its preservation of collateral flow may be related to its reduction of ischemic damage in the microvasculature.