OXIDATIVE STRESS DURING REPERFUSION OF HUMAN HEARTS - POTENTIAL SOURCES OF OXYGEN-FREE RADICALS

Objective: The aim was to examine the role of neutrophil activation in the genesis of oxidative stress during the early phases of reperfusio n after ischaemia in patients subjected to aortocoronary bypass grafti ng. Methods: Ten selected patients were studied. All had normal ejecti on fraction and normal left ventricular end diastolic pressures before operation. Each patient required at least three grafts, so that the d uration of aortic crossclamping exceeded 30 min, the minimum ischaemic period required to detect oxidative stress upon reperfusion. Oxidativ e stress was assessed by measuring the formation and release of oxidis ed glutathione (GSSG) in the coronary sinus 1 min before and 3 min aft er the start of the cardiopulmonary bypass, and then 1, 5, 10, and 20 min after removal of the aortic clamp, and again 5 and 10 min after th e end of the cardiopulmonary bypass. The arterial-coronary sinus diffe rence for neutrophils, elastase-a, protease complex (elastase), and cr eatine phosphokinase was also monitored at the same intervals. Results : Before clamping, GSSG was undetectable in arterial and coronary sinu s blood. There was no significant arterial-coronary sinus difference f or neutrophils or elastase [53(SEM 66) cell.ml(-1) and 1.10(2.49) mu g .litre(-1), respectively]. Five minutes after re-establishment of coro nary blood flow, there was both a release of GSSG into the coronary si nus [arterial-coronary sinus difference: 11(2.6) nmol.dl(-1)] and an a ccumulation of neutrophils in the heart [arterial-coronary sinus diffe rence: 262(33), P < 0.01 cell.ml(-1)], whereas no elastase release fro m the heart was measured [arterial-coronary sinus difference 7.6(4.46) mu g.litre(-1), NS]. The arterial levels of elastase increased progre ssively during the operation from 48(5) mu g.litre(-1) (preclamping) t o 405(62) mu g.litre(-1), P < 0.01 (end of the cardiopulmonary bypass) . Conclusions: These data indicate that, in man, neutrophils do accumu late in the myocardium during early reperfusion. However, they are not activated when oxidative stress occurs. It is unlikely that the neutr ophil localisation in the heart has pathological significance in the p roduction of oxygen free radicals during early reperfusion. Free radic al accumulation in the coronary vessels may contribute to disorders of coronary flow associated with reperfusion.