Alpha-2 adrenergic antagonism enhances risk of ventricular tachycardia during acute ischemia

Scand Cardiovasc J. 2007 Dec;41(6):378-85. doi: 10.1080/14017430701487713.

Abstract

Objective: In this study we tested the hypothesis that alpha-2 adrenergic antagonism could facilitate induction of previously non-inducible ventricular tachycardia (VT) during acute ischemia. Previous reports suggest that VT during ischemia may be modulated by (alpha-2 adrenergic agonists.

Design: The left anterior descending artery was occluded after instrumentation of the ischemic risk zone with 21 multipolar plunge needles, each recording 6 bipolar electrograms. Three dimensional mapping characterized the mechanism of VT induced with extrastimuli.

Results: Of 16 non-inducible dogs included, eight which were given the alpha-2 adrenergic antagonist yohimbine all had inducible VT, while all eight in the control group remained non-inducible (p < 0.05). Six of the VTs were of focal Purkinje origin. The cycle length of the VTwas 119 +/- 4 ms. Mean arterial pressure (81+/- 8 to 82 +/- 8 mmHg, p = ns), ventricular effective refractory period (146 +/- 6 to 144 +/- 5 ms, p = ns) and ischemic zone size (55 +/-6% vs. 61 +/- 4%, p = 0.45) were not altered by yohimbine indicating minimal central or pre-junctional effects of the drug.

Conclusions: Yohimbine facilitates induction of VT, especially those with focal Purkinje fiber origin, suggestive of an effect mediated through antagonism of post-junctional alpha-2 adrenoceptors on Purkinje fibers.

MeSH terms

  • Adrenergic alpha-Antagonists / adverse effects*
  • Animals
  • Disease Models, Animal
  • Dogs
  • Electrocardiography
  • Electrophysiologic Techniques, Cardiac
  • Female
  • Male
  • Myocardial Ischemia / drug therapy*
  • Purkinje Fibers / drug effects
  • Purkinje Fibers / physiopathology
  • Receptors, Adrenergic, alpha-2 / drug effects
  • Tachycardia, Ventricular / chemically induced*
  • Tachycardia, Ventricular / physiopathology
  • Yohimbine / adverse effects*

Substances

  • Adrenergic alpha-Antagonists
  • Receptors, Adrenergic, alpha-2
  • Yohimbine