Copyright © 1993 by the European Society of Cardiology.
© 1993 The European Society of Cardiology
Myocardial damage during ischaemia and reperfusion
Cattedra di Cardiologia, Universita' di Brescia Brescia
* Centro di Fisiopatologia Cardiovasculai "Salvatore Maugeri", Fondazione Clinica del Lavoro Centro di Gussago Brescia, Italy
II Divisione di Cardiochirurgia, Spedali Civil Brescia, Italy
Correspondence: Prof. Roberto Ferrari, Cattedra di Cardiologia, Universita' degil Studi di Brescia, c/o Spedali Civili, P. le Spedali Civili, 1.25123 Brescua, Italy
Reperfusion, without doubt, is the most effective way to treat the ischaemic myocardium. Late reperfusion may, however, cause further damage. We attempted to identify the nature and time-course of metabolic changes occurring during ischaemia followed by reperfusion either in isolated and perfused rabbit hearts or in coronary artery disease (CAD) patients undergoing intracoronary thrombolysis or aortocoronary bypass grafting. In isolated hearts, reperfusion after prolonged ischaemia causes exacerbation of cell damage, leading to a breakdown of the permeability barrier of ions as well as of larger molecules, such as creatine phosphokinase. As consequence, reperfusion results in a large increase in intracellular calcium, leading to mitochondrial calcium overload with subsequent damage to the mitochondrial structure and loss of the ability to produce adenosine triphosphate (ATP). The ultimate mediator of the membrane damage is not known. It has been suggested that myocardial production of oxygen free radicals above the neutralizing capacity of the myocytes is an important cause of reperfusion damage. There is evidence that prolonged ischaemia reduces the naturally occurring defence mechanisms of the heart against oxygen free radicals, particularly mitochondrial manganese superoxide dismutase, and the intracellular pool of reduced glutathione. Consequently, reperfusion results in severe oxidative damage, as evidenced by tissue accumulation and release of oxidized glutathione. An oxygen free radical-mediated impairment of mechanical function also occurs during reperfusion of the human heart. During surgical reperfusion of CAD patients, we observed a prolonged and sustained release of oxidized glutathione; the degree of oxidative stress was inversely correlated with recovery of mechanical and haemodynamic function. These findings represent the rationale for therapeutic interventions which increase cellular antioxidant capacities and improve the efficacy of myocardial reperfu
Key Words: Oxygen free radicals • myocardial ischaemia • myocardial reperfusion • heart metabolism • thrombolysis