This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Priori, S. G. Articles by Corr, P. B. Search for Related Content PubMed PubMed Citation Articles by Priori, S. G. Articles by Corr, P. B. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB POTASSIUM

Circulation, Vol 83, 248-259, Copyright © 1991 by American Heart Association

ARTICLES

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

SG Priori, KA Yamada and PB Corr
Department of Internal Medicine, Washington University School of Medicine, St. Louis, Mo 63110.

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 beta- but not alpha-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 on alpha- and beta- 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 alpha-agonist phenylephrine (10(- 5) or 10(-7) M, with 10(-5) M nadolol) or the beta-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 alpha- (12 of 13 cells) and beta-adrenergic (five of five cells) stimulation. Increasing [K+]o during moderate hypoxia completely abolished the afterdepolarizations induced by alpha-adrenergic stimulation and prevented the occurrence of triggered activity. In contrast, the influence of beta-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 alpha- and beta-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.

This article has been cited by other articles:

				N. Dzimiri Regulation of beta -Adrenoceptor Signaling in Cardiac Function and Disease Pharmacol. Rev., September 1, 1999; 51(3): 465 - 502. [Abstract] [Full Text] [PDF]