Diabetes enhances leukocyte accumulation in the coronary microcirculation early in reperfusion following ischemia

Background: Diabetic hearts are particularly vulnerable to ischemia-reperfu sion injury. For leukocytes to participate in ischemia-reperfusion injury, they must first sequester in the microcirculation. The aim of this study wa s to determine, by direct observation, if early leukocyte deposition was in creased in the diabetic coronary microcirculation early in reperfusion foll owing myocardial ischemia. Methods: Non-diabetic and streptozotocin (STZ)-i nduced diabetic rat hearts, subjected to 30 min of 37 degrees C, no-flow is chemia, were initially reperfused with blood containing labeled leukocytes. The deposition of fluorescent leukocytes in coronary capillaries and venul es was directly visualized and recorded using intravital fluorescence micro scopy. In addition, flow cytometry was used to measure CD11b adhesion molec ule expression on polymorphonuclear (PMN) leukocytes from non-diabetic and STZ-diabetic rats. Results: in the nun-diabetic, control hearts, early in r eperfusion, leukocytes trapped in coronary capillaries and adhered to the w alls of post-capillary venules. In the diabetic hearts, leukocyte trapping in capillaries and adhesion to venules were both significantly increased (P < 0.05). PMN CD11b expression was also significantly increased in the diab etic blood compared to the non-diabetic blood (P < 0.05). Conclusions. Earl y in reperfusion following myocardial ischemia, leukocytes rapidly accumula te in greater numbers in the coronary microcirculation of the diabetic hear t by both trapping in coronary capillaries and by adhering to venules. The enhanced retention of leukocytes in the diabetic coronary microcirculation increases the likelihood of inflammation-mediate reperfusion injury and may explain, in part, the poor recovery of diabetic hearts from an ischemic ev ent. (C) 2000 Elsevier Science Inc. All rights reserved.