Abnormal automatic rhythms in ischemic Purkinje fibers are modulated by a specific alpha 1-adrenergic receptor subtype.

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  • Author(s): Anyukhovsky EP;Anyukhovsky EP; Rosen MR
  • Source:
    Circulation [Circulation] 1991 Jun; Vol. 83 (6), pp. 2076-82.
  • Publication Type:
    Journal Article; Research Support, Non-U.S. Gov't; 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:
      Heart Rate*/drug effects; Coronary Disease/*physiopathology ; Purkinje Fibers/*physiopathology ; Receptors, Adrenergic, alpha/*physiology; Adrenergic alpha-Antagonists/pharmacology ; Animals ; Arrhythmias, Cardiac/etiology ; Calcium/metabolism ; Clonidine/analogs & derivatives ; Clonidine/pharmacology ; Coronary Disease/metabolism ; Dioxanes/pharmacology ; Dogs ; Extracellular Space/metabolism ; Phenylephrine/pharmacology ; Propranolol/pharmacology
    • Abstract:
      Background: Recent advances in adrenergic pharmacology have made possible the identification of alpha 1-adrenergic receptor subtypes using the specific blockers chloroethylclonidine and WB 4101.
      Methods and Results: In the present study, we used these two blockers to determine the mechanisms responsible for automatic rhythms occurring during simulated ischemia and reperfusion of isolated canine Purkinje fibers. Experiments were done in the presence of propranolol to minimize beta-adrenergic contributions to the rhythms studied. In the control situation, all fibers showed membrane potentials greater than -90 mV and normal automatic rhythms. During simulated ischemia, membrane potential depolarized to the -60 mV range. Abnormal automaticity was seen in 20% of fibers not treated with phenylephrine and in 50% of those superfused with 1 x 10(-7) M phenylephrine. The incidence of abnormal automaticity was reduced to 0% by WB 4101 (which blocks phosphoinositide metabolic effects of alpha 1-adrenergic stimulation in the heart) and was increased to 90% by chloroethylclonidine (which blocks Na-K pump-stimulating effects of alpha-agonists). Moreover, the ischemic fibers were significantly more hyperpolarized during superfusion with WB 4101 than with chloroethylclonidine. Triggered activity induced by delayed or early after depolarizations was not seen in any experiment.
      Conclusions: Automatic arrhythmias induced by alpha 1-adrenergic stimulation during simulated ischemia may be attributed to a specific alpha 1-adrenergic receptor subtype that is blocked by WB 4101. These results have important implications with respect to the induction of arrhythmias in the setting of ischemia and the means for their prevention or treatment.
    • Grant Information:
      HL-28223 United States HL NHLBI NIH HHS; HL-28958 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)
      9Y8NXQ24VQ (Propranolol)
      E9H51OIT2B ((2-(2',6'-dimethoxy)phenoxyethylamino)methylbenzo-1,4-dioxane)
      MN3L5RMN02 (Clonidine)
      SY7Q814VUP (Calcium)
    • Publication Date:
      Date Created: 19910601 Date Completed: 19910708 Latest Revision: 20190623
    • Publication Date:
      20221213
    • Accession Number:
      10.1161/01.cir.83.6.2076
    • Accession Number:
      1674901