Influence of leukopenia on collateral flow, reperfusion flow, reflow ventricular fibrillation, and infarct size in dogs.

Leukocytes contribute to myocardial damage during ischemia and reperfusion. However, the mechanism involved has not been clearly elucidated. The purpose of the present study was to determine whether leukocyte-induced myocardial damage is flow mediated. In open-chest dogs submitted to 2 hours of ischemia, area at risk, infarct size, and regional myocardial blood flow before, during, and after ischemia were measured. Leukopenia was induced by a two-step method (chemotherapy and antineutrophil serum) in a group of 14 dogs as compared to a control group of 18 dogs. The relation of infarct size to the major determinants of infarct size was analyzed by uni- and multilinear regressions. Seven control dogs had ventricular fibrillation at reperfusion compared to one dog with leukopenia. In the group with leukopenia the mean infarct size was smaller (31.1 +/- 5.8% of area at risk) than in the control group (47.7 +/- 2.9, p = 0.02). In addition, the two multiple linear regression equations were significantly different (p = 0.01). Myocardial blood flow to the central ischemic zone did not change significantly between 20 and 120 minutes of ischemia in the control dogs (n = 12; subendocardial = 0.08 +/- 0.03 vs 0.07 +/- 0.03 ml/min/gm; subepicardial = 0.20 +/- 0.07 vs 0.20 +/- 0.05 ml/min/gm) and in the dogs with leukopenia (n = 12; 0.07 +/- 0.02 vs 0.07 +/- 0.02 ml/min/gm and 0.15 +/- 0.004 vs 0.18 +/- 0.04 ml/min/gm). A similar reduction in myocardial blood flow was observed after 6 hours of reperfusion in the control dogs (0.34 +/- 0.07 ml/min/gm vs 1.02 +/- 0.11 at baseline, p less than 0.01) and in the dogs with leukopenia (0.25 +/- 0.04 vs 0.81 +/- 0.08 ml/min/gm, p less than 0.01). It was concluded that the leukocyte-dependent myocardial injury did not appear to be mediated through a flow mechanism during either ischemia or reperfusion.