AJP - Heart and Circulatory Physiology, Vol 251, Issue 2 314-H323, Copyright © 1986 by American Physiological Society

ARTICLES

Role of leukocytes in response to acute myocardial ischemia and reflow in dogs

R. L. Engler, M. D. Dahlgren, D. D. Morris, M. A. Peterson and G. W. Schmid-Schonbein

Recent evidence indicates that leukocytes (LEU) are large, stiff, viscous cells that naturally adhere to vascular endothelium. Their broad role in the early myocardial microvascular response to acute ischemia was suggested by 1) the role of leukocyte capillary plugging in the no-reflow phenomenon, 2) resistance increases in skeletal muscle with LEU infusions, and 3) salvage of ischemic myocardium by anti-LEU agents. We perfused the coronary circulation under matched, controlled conditions with whole blood or granulocyte-depleted whole blood. During 1 h of ischemia (left anterior descending occlusion) circumflex perfusion pressure was servocontrolled to a constant value. In whole blood-perfused hearts, flow measured by the radiolabeled microsphere method decreased in endocardium from 0.12 +/- 0.05 at 5 min of ischemia to 0.09 +/- 0.04 ml X min-1 X g-1 at 60 min of ischemia and in epicardium from 0.27 +/- 0.17 to 0.21 +/- 0.16 ml X min-1 X g-1, both P less than 0.05. In granulocyte-depleted blood-perfused hearts, flow increased over the same period from 0.18 +/- 0.15 to 0.29 +/- 0.18 ml X min-1 X g-1 in endocardium (P less than 0.05) and did not change significantly in epicardium (0.36 +/- 0.22 to 0.41 +/- 0.24 ml X min-1 X g-1). The LEU-depleted blood perfusate contained less than 33 granulocytes/microliter, whereas control perfusate contained 4,265/microliter. Reperfusion at normal pressures with carbon suspension allowed for histologic evaluation of the no-reflow phenomenon. With whole blood perfusion the no-reflow phenomenon in the endocardium was present with 27% of capillaries occluded, compared with nearly complete reperfusion in LEU-depleted animals (1% of capillaries occluded, P less than 0.05). Furthermore, LEU depletion prevented the increases in tissue water content seen in control hearts and decreased the incidence of ventricular arrhythmias. These studies demonstrate the significant participation of granulocytes in the unfavorable responses of flow, edema formation, and arrhythmias to the 1st h of myocardial ischemia and further document their role in the no-reflow phenomenon.

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