With the use of isolated working guinea pig hearts with normothermic global ischemia, it was shown that 5,5-dimethyl-pirroline-N-oxide (DMPO), an organic spin trap agent designed specifically to form stable adducts with oxygen free radicals in electron spin resonance studies, can dramatically reduce te vulnerability of the heart to reperfusion-induced arrhythmias. Studied in concentrations ranging from 10 to 500 μmol/L, DMPO exerted a dose-dependent protective effect. Thus, after 30 minutes of global ischemia, the incidence of ventricular fibrillation (total) and tachycardia was reduced from control values of 100% and 100% to 100% and 100%, 91% and 100%, 25% (p < 0.001) and 50%(p < 0.05), and 25% (p < 0.001) and 41% (p < 0.05), respectively, with DMPO concentrations of 10, 30, 100, and 500 μmol/L. Maximum signals of DMPO-OH adduct, with the use of electron spin resonance studies, were observed after 3 minutes of reperfusion in fibrillated hearts but were not detected in nonfibrillated hearts. Results of nuclear magnetic resonance studies of myocardial adenosine triphosphate, creatine phosphate, pH, and inorganic phosphate showed that these parameters were not significantly changed by treatment with DMPO, and consequently myocardial heart function was not improved, although there was a dissociation between myocardial adenosine triphosphate content and left ventricular developed pressure during reperfusion. The data presented here indicate that oxygen free radicals play an important role in the development of reperfusion-induced arrhythmias but trapping these cytotoxic free radicals does not improve the recovery of postischemic heart function and high-energy phosphate contents in isolated working guinea pig hearts.
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine