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 reperfusion after ischaemia in patients subjected to aortocoronary bypass grafting. Methods: Ten selected patients were studied. All had normal ejection fraction and normal left ventricular end diastolic pressures before operation. Each patient required at least three grafts, so that the duration of aortic crossclamping exceeded 30 min, the minimum ischaemic period required to detect oxidative stress upon reperfusion. Oxidative stress was assessed by measuring the formation and release of oxidised glutathione (GSSG) in the coronary sinus 1 min before and 3 min after 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 the end of the cardiopulmonary bypass. The arterial-coronary sinus difference for neutrophils, elastase-a, protease complex (elastase), and creatine phosphokinase was also monitored at the same intervals. Results: Before clamping, GSSG was undetectable in arterial and coronary sinus blood. There was no significant arterial-coronary sinus difference for 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 coronary blood flow, there was both a release of GSSG into the coronary sinus [arterial-coronary sinus difference: 11(2.6) nmol.dl(-1)] and an accumulation of neutrophils in the heart [arterial-coronary sinus difference: 262(33), P < 0.01 cell.ml(-1)], whereas no elastase release from the heart was measured [arterial-coronary sinus difference 7.6(4.46) mu g.litre(-1), NS]. The arterial levels of elastase increased progressively during the operation from 48(5) mu g.litre(-1) (preclamping) to 405(62) mu g.litre(-1), P < 0.01 (end of the cardiopulmonary bypass). Conclusions: These data indicate that, in man, neutrophils do accumulate in the myocardium during early reperfusion. However, they are not activated when oxidative stress occurs. It is unlikely that the neutrophil localisation in the heart has pathological significance in the production of oxygen free radicals during early reperfusion. Free radical accumulation in the coronary vessels may contribute to disorders of coronary flow associated with reperfusion.