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.
Ceconi
C
C
University of Brescia, Italy.
Curello
S
S
Cargnoni
A
A
Boffa
G M
GM
Ferrari
R
R
D000818:Animals; D003402:Creatine Kinase / Q000378:metabolism; D004112:Dimercaprol / Q000627:therapeutic use*; D016166:Free Radical Scavengers; D005978:Glutathione / Q000378:metabolism; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D008297:Male; D008929:Mitochondria, Heart / Q000502:physiology; D009200:Myocardial Contraction / Q000187:drug effects; D015425:Myocardial Reperfusion; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism; D011292:Premedication; D011817:Rabbits; D013438:Sulfhydryl Compounds / Q000378:metabolism; D013997:Time Factors
D016166:Free Radical Scavengers; D007773:Lactates; D013438:Sulfhydryl Compounds; D004112:Dimercaprol; D019344:Lactic Acid; D003402:Creatine Kinase; D005978:Glutathione