Oxygen Free Radical‐Mediated Heart Injury in Animal Models and during Bypass Surgery in Humans Effects of α‐Tocopherola

There is evidence that oxygen free radicals play a role in myocardial ischemic and reperfusion injury. We investigated the effect of ischemia and reperfusion on glutathione status. Reperfusion after prolonged ischemia (60 min) induced an important release of reduced (GSH) and oxidized (GSSG) glutathione, concomitant with an increase of tissue GSSG and no recovery of mechanical function, indicating that reperfusion results in oxidative stress. These alterations are associated with tissue and mitochondrial calcium accumulation, loss of mitochondrial function, and membrane damage. We also determined the arteriocoronary sinus difference for GSH and GSSG of 16 CAD patients undergoing coronary artery bypass. Patients were divided in two groups according to the length of clamping period: 25 +/- 2 min (group 1), and 55 +/- 6 min (group 2). In group 1, reperfusion resulted in a transient release of GSH, GSSG, CPK, and lactate, with return to preclamping values in 10 minutes. In group 2, reperfusion determined a sustained and pronounced release of GSH, GSSG, CPK, and lactate during declamping, suggesting the occurrence of an oxidative stress. Using an in vitro model, administration of alpha-tocopherol bound with albumin showed protection of mitochondrial function, improved recovery of contraction, and reduced oxidative stress during reperfusion.