An alpha-1-adrenergic receptor subtype is responsible for delayed afterdepolarizations and triggered activity during simulated ischemia and reperfusion of isolated canine Purkinje fibers.

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  • Author(s): Molina-Viamonte V;Molina-Viamonte V; Anyukhovsky EP; Rosen MR
  • Source:
    Circulation [Circulation] 1991 Oct; Vol. 84 (4), pp. 1732-40.
  • Publication Type:
    Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: Lippincott Williams & Wilkins Country of Publication: United States NLM ID: 0147763 Publication Model: Print Cited Medium: Print ISSN: 0009-7322 (Print) Linking ISSN: 00097322 NLM ISO Abbreviation: Circulation Subsets: MEDLINE
    • Publication Information:
      Publication: Hagerstown, MD : Lippincott Williams & Wilkins
      Original Publication: [Dallas, Tex., etc., American Heart Association, etc.]
    • Subject Terms:
      Arrhythmias, Cardiac/*etiology ; Myocardial Reperfusion Injury/*physiopathology ; Purkinje Fibers/*physiopathology ; Receptors, Adrenergic, alpha/*physiology; Adrenergic alpha-Antagonists/pharmacology ; Animals ; Arrhythmias, Cardiac/physiopathology ; Clonidine/analogs & derivatives ; Clonidine/pharmacology ; Dioxanes/pharmacology ; Dogs ; Myocardial Reperfusion Injury/etiology ; Phenylephrine/pharmacology ; Receptors, Adrenergic, alpha/drug effects
    • Abstract:
      Background: We used standard microelectrode techniques to study delayed afterdepolarizations and triggered activity induced by alpha 1-adrenergic stimulation in canine Purkinje fibers in the setting of simulated ischemia and reperfusion.
      Methods and Results: The ischemic environment included 10.8 mM [Ca2+]o, 10 mM [K+]o, 40-50 mm Hg PO2, 20 mM lactate (pH 6.7), and 1 x 10(-7) M phenylephrine. During ischemia, there was the variable occurrence of abnormal automaticity, early afterdepolarizations, and delayed afterdepolarizations. During reperfusion, 100% of preparations manifested delayed afterdepolarizations and 40% manifested triggered activity. Decreasing PO2 to less than 20 mm Hg markedly reduced the incidence of delayed afterdepolarizations and triggered activity, as did increasing PO2 to values of more than 90 mm Hg. WB 4101, an alpha 1-subtype-selective competitive blocker that antagonizes the effects of alpha 1-agonists to induce phosphoinositide metabolism and increase [Ca2+]i, significantly reduced the incidence of delayed afterdepolarizations and triggered activity. In contrast, the alpha 1-subtype-selective blocker chloroethylclonidine, an alkylating agent, had no effect on afterdepolarizations or triggered activity.
      Conclusions: Our results indicate that a specific alpha 1-adrenergic pathway is involved in the induction of triggered activity in the setting of ischemia and reperfusion and suggest that interventions used to block this specific pathway have the potential to be antiarrhythmic. They also emphasize the importance of the magnitude of hypoxia in the expression of the arrhythmias.
    • Grant Information:
      HL-28223 United States HL NHLBI NIH HHS; HL-43731 United States HL NHLBI NIH HHS
    • Accession Number:
      0 (Adrenergic alpha-Antagonists)
      0 (Dioxanes)
      0 (Receptors, Adrenergic, alpha)
      1WS297W6MV (Phenylephrine)
      3X825O680H (chlorethylclonidine)
      E9H51OIT2B ((2-(2',6'-dimethoxy)phenoxyethylamino)methylbenzo-1,4-dioxane)
      MN3L5RMN02 (Clonidine)
    • Publication Date:
      Date Created: 19911001 Date Completed: 19911101 Latest Revision: 20190623
    • Publication Date:
      20221208
    • Accession Number:
      10.1161/01.cir.84.4.1732
    • Accession Number:
      1680578