Antioxidant protection against damage during cardiac ischemia and reperfusion: effect of dimercapto-propanol

Oxygen-derived free radicals and their metabolites may contribute to the extension of cellular injury that occurs on reperfusion of the ischemic myocardium; and therapy directed against the toxic effects of reactive oxygen species has provided protection to the ischemic myocardium which undergoes subsequent reperfusion. We evaluated the effectiveness of dimercapto-propanol (1,2-dimercapto-propanol, British Anti-Lewisite, dimercaprol) to limit the extent of myocardial damage resulting from 60 minutes of severe ischemia followed by 30 minutes of reperfusion in the Langendorff-perfused rabbit heart. Dimercaptopropanol is a thiol agent, with two free sulfhydryl groups per molecule, which has no effect on glutathione status nor on the total tissue thiol pool. Pretreatment of the hearts with 10(-6) M dimercapto-propanol resulted in marked myocardial protection, measured in terms of preserved mechanical function and reduced creatine kinase release. On reperfusion less oxidative stress developed. The beneficial effects of dimercapto-propanol could not be explained by hemodynamic differences or effects on energy metabolism. In addition, it is unlikely that dimercapto-propanol acts as a free radical scavenger at the concentrations employed. The protection may be achieved by the drug keeping some key sulfhydryl groups of functional proteins in the reduced state.