Low-flow reperfusion after myocardial ischemia enhances leukocyte accumulation in coronary microcirculation

During early reperfusion after myocardial ischemia, the mechanisms responsible for leukocyte accumulation in the heart are unclear. We examined the effects of reducing coronary blood flow during reperfusion on leukocyte accumulation in coronary capillaries and postcapillary venules. Isolated rat hearts were perfused for 30 min and then subjected to 30 min of 37°C, no- flow ischemia. The deposition of fluorescently labeled leukocytes was observed directly in coronary capillaries and venules using intravital microscopy after 5, 20, and 35 min of reperfusion. Blood cell velocity was measured in venules after 5 min of reperfusion (R₅) and shear rate (s^-1) was calculated. Four groups were studied: nonischemic control (NIC) hearts and postischemic hearts reperfused at full flow (I/R₁₀₀) and at 50 and 10% of full flow (I/R₅₀ and I/R₁₀, respectively). In I/R₁₀₀ hearts, there was a significant increase in leukocyte trapping in capillaries compared with the NIC group (R₅: 5.7 ± 0.6 vs. 2.0 ± 0.4 leukocytes/capillary field, respectively; P < 0.05). However, the increase in leukocyte adhesion to venules was not statistically significant compared with NIC (R₅: 3.2 ± 0.4 vs. 1.5 ± 0.6 leukocytes/100-μm venule, respectively; P < 0.2). In I/R₅₀ hearts, a further increase in leukocyte accumulation occurred in the capillaries but not in the venules. However, in I/R₅₀ hearts, there was a statistically significant increase in both capillaries (R₅: 9.2 ± 0.8; P < 0.05) and venules (R₅: 4.4 ± 0.5; P < 0.05). When leukocyte margination in coronary venucles was examined as a function of venular shear rate, a significant correlation (r = 0.99, P < 0.05) was found. These results suggest that, after ischemia, a reduction in reflow enhances leukocyte trapping in capillaries and that leukocyte adhesion in venules is inversely related to shear rate. Enhanced leukocyte accumulation may in turn increase the leukocyte contribution to early reperfusion in jury in the heart.