The role of heme oxygenase-related carbon monoxide and ventricular fibrillation in ischemic/reperfused hearts

I. Bak, Gabor Papp, Tibor Turoczi, E. Varga, Levente Szendrei, M. Vecsernyés, Ferenc Joo, A. Tósaki

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

Reperfusion-induced ventricular fibrillation (VF) and heme oxygenase (HO)-related carbon monoxide (CO) production in isolated ischemic/reperfused rat hearts were studied by gas chromatography. Hearts were subjected to 30 min ischemia followed by 2 h reperfusion, and the expression of HO-1 mRNA (about 4-fold) was observed in ischemic/reperfused-nonfibrillated hearts. In fibrillated hearts, the reduction (about 75%) in HO-1 mRNA expression was detected. These changes in HO-1 mRNA expression were reflected in tissue CO production. Thus, in the absence of VF, CO production was increased about 3.5-fold, while in the presence of VF, CO production was under the detectable level in comparison with the control group. Our results suggest that the stimulation of HO-1 mRNA expression may lead to the prevention of reperfusion VF via an increase in endogenous CO production. To prove this, hearts were treated with 1 μM of N-tert-butyl-α-phenylnitrone (PBN) as an inducer of HO-1. PBN treatment resulted in about 20 times increase in HO-1 mRNA expression, and even a higher production rate in endogenous CO. HO protein level and enzyme activity followed the same pattern, as it was observed in HO-1 mRNA expression, in fibrillated and nonfibrillated myocardium. Five mM/l of zinc-protoporphyrin IX (ZnPPIX) significantly blocked HO enzyme activity and increased the incidence of VF, therefore the application of ZnPPIX led to a significant reduction in HO-1 mRNA and protein expression. Our data provide direct evidence of an inverse relationship between the development of reperfusion-induced VF and endogenous CO production. Thus, interventions that are able to increase tissue CO content may prevent the development of reperfusion-induced VF.

Original languageEnglish
Pages (from-to)639-648
Number of pages10
JournalFree Radical Biology and Medicine
Volume33
Issue number5
DOIs
Publication statusPublished - Sep 1 2002

Fingerprint

Heme Oxygenase (Decyclizing)
Heme Oxygenase-1
Ventricular Fibrillation
Carbon Monoxide
Reperfusion
Messenger RNA
Enzyme activity
Tissue
Enzymes
Gas chromatography
Gas Chromatography
Rats
Myocardium
Proteins
Ischemia
Control Groups
Incidence

Keywords

  • Carbon monoxide
  • Cardiac function
  • Free radicals
  • Heme oxygenase
  • Ischemia
  • Isolated heart
  • Reperfusion
  • Ventricular fibrillation

ASJC Scopus subject areas

  • Medicine(all)
  • Toxicology
  • Clinical Biochemistry

Cite this

The role of heme oxygenase-related carbon monoxide and ventricular fibrillation in ischemic/reperfused hearts. / Bak, I.; Papp, Gabor; Turoczi, Tibor; Varga, E.; Szendrei, Levente; Vecsernyés, M.; Joo, Ferenc; Tósaki, A.

In: Free Radical Biology and Medicine, Vol. 33, No. 5, 01.09.2002, p. 639-648.

Research output: Contribution to journalArticle

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abstract = "Reperfusion-induced ventricular fibrillation (VF) and heme oxygenase (HO)-related carbon monoxide (CO) production in isolated ischemic/reperfused rat hearts were studied by gas chromatography. Hearts were subjected to 30 min ischemia followed by 2 h reperfusion, and the expression of HO-1 mRNA (about 4-fold) was observed in ischemic/reperfused-nonfibrillated hearts. In fibrillated hearts, the reduction (about 75{\%}) in HO-1 mRNA expression was detected. These changes in HO-1 mRNA expression were reflected in tissue CO production. Thus, in the absence of VF, CO production was increased about 3.5-fold, while in the presence of VF, CO production was under the detectable level in comparison with the control group. Our results suggest that the stimulation of HO-1 mRNA expression may lead to the prevention of reperfusion VF via an increase in endogenous CO production. To prove this, hearts were treated with 1 μM of N-tert-butyl-α-phenylnitrone (PBN) as an inducer of HO-1. PBN treatment resulted in about 20 times increase in HO-1 mRNA expression, and even a higher production rate in endogenous CO. HO protein level and enzyme activity followed the same pattern, as it was observed in HO-1 mRNA expression, in fibrillated and nonfibrillated myocardium. Five mM/l of zinc-protoporphyrin IX (ZnPPIX) significantly blocked HO enzyme activity and increased the incidence of VF, therefore the application of ZnPPIX led to a significant reduction in HO-1 mRNA and protein expression. Our data provide direct evidence of an inverse relationship between the development of reperfusion-induced VF and endogenous CO production. Thus, interventions that are able to increase tissue CO content may prevent the development of reperfusion-induced VF.",
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AU - Turoczi, Tibor

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AU - Szendrei, Levente

AU - Vecsernyés, M.

AU - Joo, Ferenc

AU - Tósaki, A.

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