DMPO and reperfusion injury

Arrhythmia, heart function, electron spin resonance, and nuclear magnetic resonance studies in isolated working guinea pig hearts

A. Tósaki, Pierre Braquet

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44 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)819-830
Number of pages12
JournalAmerican Heart Journal
Volume120
Issue number4
DOIs
Publication statusPublished - 1990

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Electron Spin Resonance Spectroscopy
Reperfusion Injury
Oxides
Cardiac Arrhythmias
Guinea Pigs
Magnetic Resonance Spectroscopy
Reperfusion
Free Radicals
Reactive Oxygen Species
Ischemia
Adenosine Triphosphate
Phosphates
Phosphocreatine
Ventricular Fibrillation
Ventricular Pressure
Ventricular Tachycardia
Incidence

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

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title = "DMPO and reperfusion injury: Arrhythmia, heart function, electron spin resonance, and nuclear magnetic resonance studies in isolated working guinea pig hearts",
abstract = "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.",
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T2 - Arrhythmia, heart function, electron spin resonance, and nuclear magnetic resonance studies in isolated working guinea pig hearts

AU - Tósaki, A.

AU - Braquet, Pierre

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N2 - 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.

AB - 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.

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