Neutrophil depletion does not prevent myocardial dysfunction after brief coronary occlusion

AbstractRecent evidence suggests that oxygen free radicals generated during ischemia or reperfusion may contribute to myocardial dysfunction after brief coronary occlusion (“myocardial stunning”). Because neutrophil leukocytes represent a potential source of oxygen radicals, the concept of whether depletion of neutrophils could attenuate myocardial stunning after 10 min of ischemia was examined. In 16 anesthetized dogs, the left anterior descending coronary artery was perfused by an extracorporeal circuit, either with (n = 8) or without (n = 8) neutrophil filters in the perfusion line. The group with filters had near total absence of neutrophils in blood perfusing the left anterior descending coronary artery territory (16 ± 8 versus 1,826 ± 399/μl in the control group). Systolic myocardial shortening and end-systolic pressure-segment length relations were recorded during rest conditions and during incremental intracoronary infusion of dobutamine (5 to 15 μg/min) before and after 10 min of coronary flow occlusion.Before coronary occlusion, systolic myocardial shortening at rest was similar in control (15.4 ± 1.7%) and neutropenic (12.4 ± 2.2%) groups. Dobutamine (15 μg/ min) resulted in increased shortening in both control (18.2 ± 1.4%, p < 0.01) and neutropenic (15.8 & 1.5%, p < 0.05) groups and in a leftward shift of the end-systolic pressure-length relation. During coronary occlusion, collateral coronary flow to the left anterior descending coronary artery territory was not significantly different in the control (0.10 ± 0.03 ml/min per g) and neutropenic (0.18 ± 0.06 ml/min per g) groups.After 20 min of reperfusion, myocardial shortening was equally reduced in both groups (control 5.6 ± 2.8%; neutropenic 4.5 ± 2.4%, p = NS versus control), and the end-systolic pressure-length relation was similarly shifted to the right, consistent with reduced myocardial contractility. Intracoronary dobutamine (15 μg/min) produced similar increases in systolic shortening in the two groups (control 10.8 ± 1.6%, p < 0.01 versus rest; neutropenic 9.6 ± 2.6%, p < 0.01 versus rest; p = NS versus control). However, myocardial shortening remained less than preocclusion levels and the end-systolic pressure-length relations remained shifted to the right, indicating persistent contractile dysfunction in both groups. These observations do not support a major role for neutrophil leukocytes in the pathogenesis of myocardial stunning after brief coronary occlusion