Isoproterenol and the genesis of reperfusion-induced arrhythmias in isolated rat heart: Adrenoceptor or free radical-mediated mechanisms?

A. Tósaki, Brian Woodward, Fumio Yamamoto, David J. Hearse

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9 Citations (Scopus)

Abstract

In the isolated rat heart, reperfusion-induced arrhythmias were exacerbated by isoproterenol (0.01-1.0 μM). The proarrhythmic action of isoproterenol was primarily the result of a β1-receptor-mediated tachycardia rather than via a free radical-mediated process, since it was prevented competitively by the β1-receptor antagonist metoprolol, but not by the free radical scavengers mannitol, superoxide dismuiase, and catalase. If heart rate was maintained by electrical pacing, the protective action of metoprolol against the isoproterenol-induced arrhythmias was lost. At high concentrations (5 and 50 μM), metoprolol alone produced a bradycardia that was probably not related to β1 blockade, and this resulted in some nonspecific antiarrhythmic activity. The data provide evidence that, in this model, heart rate during ischaemia is an important'determinant of reperfusion-induced arrhythmias, and that free radical formation from the oxidation of high levels of exogenous isoproterenol present at the time of reperfusion does not contribute in a major way to the detrimental action of isoproterenol.

Original languageEnglish
Pages (from-to)398-407
Number of pages10
JournalJournal of Cardiovascular Pharmacology
Volume15
Issue number3
Publication statusPublished - 1990

Fingerprint

Isoproterenol
Adrenergic Receptors
Reperfusion
Free Radicals
Cardiac Arrhythmias
Metoprolol
Heart Rate
Free Radical Scavengers
Mannitol
Bradycardia
Tachycardia
Superoxides
Catalase
Ischemia

Keywords

  • Catecholamines
  • Free radicals
  • Heart rate
  • Rat heart
  • Reperfusion arrhythmias

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Pharmacology

Cite this

Isoproterenol and the genesis of reperfusion-induced arrhythmias in isolated rat heart : Adrenoceptor or free radical-mediated mechanisms? / Tósaki, A.; Woodward, Brian; Yamamoto, Fumio; Hearse, David J.

In: Journal of Cardiovascular Pharmacology, Vol. 15, No. 3, 1990, p. 398-407.

Research output: Contribution to journalArticle

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