Protective effects of leukopenia and tissue plasminogen activator in microvascular ischemia-reperfusion injury

Ischemia shifts the anticoaugulant/procoagulant balance of the endothelium in favor of activation of coagulation. We studied whether cheek pouch micro circulation of leukopenic hamsters was protected by tissue plasminogen acti vator (tPA) (50 mu g/100 g body wt) against ischemia-reperfusion injury. Ad herent leukocytes, total perfused capillary length (PCL), permeability incr ease, and arteriolar and venular red blood cell (RBC) velocity were investi gated by fluorescence microscopy. Measurements were made at control, 30 or 60 min of ischemia, and at 30 or 60 min of reperfusion. Hamsters were made leukopenic by treatment with cyclophosphamide (20 mg/100 g body wt ip, 4 da ys before the experiment), which decreased circulating leukocyte count by 8 5-90%. Leukopenic hamsters undergoing 30 min of ischemia followed by 30 min of reperfusion showed no significant decrease in PCL or increased permeabi lity. Leukopenic hamsters undergoing 60 min of ischemia followed by 60 min of reperfusion presented a significant decrease in microvascular perfusion where PCL was 28 +/- 7% of baseline, low-flow conditions, and increased per meability. In leukopenic hamsters treated with tPA there was complete prote ction of capillary perfusion with no significant changes in permeability or arteriolar and venular RBC velocity. In conclusion, thrombus formation may be an additional and independent factor that with leukocyte-mediated mecha nisms determines ischemia-reperfusion injury.