DMPO and reperfusion injury: arrhythmia, heart function, electron spin resonance, and nuclear magnetic resonance studies in isolated working guinea pig hearts.
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 the vulnerability of the heart to reperfusion-induced arrhythmias. Studied in concentrations ranging from 10 to 500 mumol/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 less than 0.001) and 50% (p less than 0.05), and 25% (p less than 0.001) and 41% (p less than 0.05), respectively, with DMPO concentrations of 10, 30, 100, and 500 mumol/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.
Tosaki
A
A
Institut Henri Beaufour, Les Ulis, France.
Braquet
P
P
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology / Q000517:prevention & control*; D003497:Cyclic N-Oxides / Q000627:therapeutic use*; D004578:Electron Spin Resonance Spectroscopy; D005609:Free Radicals; D006168:Guinea Pigs; D006439:Hemodynamics / Q000187:drug effects*; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000150:complications / Q000188:drug therapy*; D009206:Myocardium / Q000737:chemistry; D010710:Phosphates / Q000032:analysis
D003497:Cyclic N-Oxides; D005609:Free Radicals; D010710:Phosphates; C017245:5,5-dimethyl-1-pyrroline-1-oxide