Influence of hypoxia on adrenergic modulation of triggered activity in isolated adult canine myocytes

S. G. Priori, K. A. Yamada, P. B. Corr

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Although findings from several reports suggest that nonreentrant or focal mechanisms contribute to the genesis of arrhythmias during early ischemia, the contribution of triggered activity arising from early or delayed afterdepolarizations has not been resolved. We have previously demonstrated that β- but not α-adrenergic stimulation induces afterdepolarizations and triggered activity in isolated normoxic myocytes. In the present study, the influence of the extent of cellular derangements as well as increases in [K+](o) and α- and β-adrenergic-mediated afterdepolarizations and triggered activity was evaluated. Adult canine myocytes were exposed to one of the following experimental conditions with simultaneous intracellular transmembrane action potential recordings: 1) low PO2 (less than 10 mm Hg, obtained using a specially designed hypoxic chamber) and low (6.8) pH; 2) low PO2, low pH, and high extracellular potassium ([K+](o)) (10 mM); or 3) severe metabolic inhibition with cyanide (10-6 M). Cells from each group were superfused with either the α-agonist phenylephrine (10-5 or 10-7 M, with 10-5 M nadolol) or the β-agonist isoproterenol (10-6 M). Moderate changes in the action potentials were observed under conditions 1 and 2 (moderate hypoxia), whereas marked but reversible changes were observed with cyanide (severe metabolic inhibition). During moderate hypoxia in normal [K+](o), delayed afterdepolarizations or triggered activity were elicited by both α- (12 of 13 cells) and β-adrenergic (five of five cells) stimulation. Increasing [K+](o) during moderate hypoxia completely abolished the afterdepolarizations induced by α-adrenergic stimulation and prevented the occurrence of triggered activity. In contrast, the influence of β-adrenergic stimulation was only attenuated by an increase in [K+](o). Exposure to cyanide completely prevented the induction of afterdepolarizations and triggered activity by both α- and β-adrenergic stimulation. Our findings indicate that moderate hypoxia in normal [K+](o) is associated with the development of adrenergic-mediated afterdepolarizations and triggered activity. In contrast, accumulation of [K+](o) or severe impairment of cellular metabolism is accompanied by inhibition of adrenergic-mediated afterdepolarizations and triggered activity.

Original languageEnglish
Pages (from-to)248-259
Number of pages12
Issue number1
Publication statusPublished - 1991


  • α-adrenergic receptors
  • β-adrenergic receptors
  • afterdepolarizations
  • arrhythmias
  • hypoxia

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine


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