Pentoxifylline reduces leukocyte retention in the coronary microcirculation early in reperfusion following ischemia

Using direct visualization techniques, we recently confirmed earlier histologic studies that leukocytes accumulate primarily in the coronary capillaries of ischemic hearts during early reperfusion. The purpose of this study was to determine if pentoxifylline (PTX) would reduce leukocyte trapping in postischemic hearts. Isolated rat hearts were subjected to 30 min of 37°C, no-flow ischemia. Hearts were initially reperfused with diluted whole blood containing fluorescent leukocytes. At 5, (R5), 20, and 35 min of reperfusion, the deposition of leukocytes inthe coronary capillaries and venules was observed directly usingintravital fluorescence microscopy. Three groups were studied: anon-ischemic control group (group I) and postischemic groups reperfused with diluted whole blood treated with vehicle group II or PTX (5 mM; group III). Postischemic reperfusion with unactivated blood caused a significant trapping of leukocytes in coronarycapillaries throughout reperfusion (R5, group I = 2.0 ± 0.3 vs. group II = 5.7 ± 0.6 leukocytes/capillary field, p< 0.05). The addition of PTX reduced capillary leukocyte trapping below control values throughout reperfusion (R5, group III = 1.6 ± 0.2 leukocytes/capillary field, p < 0.05). At R5, there was no statistically significant difference inleukocyte accumulation in venules for all groups (group I = 1.5 ± 0.6, group II = 3.2 ± 0.4, group III = 3.3 ± 0.4 leukocytes/100 μm venule). During the reperfusion period, leukocyte persistence in the capillaries of postischemic hearts (36%) was greater than in the venules (13%). These data indicate that early in reperfusion after myocardial ischemia, leukocyte trapping occurs primarily in the coronary capillaries. PTX reduced early leukocyte trapping in the capillaries. The results also demonstrate that during reperfusion, the mechanisms affectingcapillary retention are more persistent than those in the venule. These findings suggest that attempts to attenuate the damagingpotential of early leukostasis in capillaries consider the biophysical properties of the leukocyte.