Effect of alpha 1-adrenergic receptor antagonists on susceptibility to malignant arrhythmias: protection from ventricular fibrillation

Journal of Cardiovascular Pharmacology
G E Billman

Abstract

alpha-Adrenergic receptor responsiveness has been reported to increase during myocardial ischemia, correlating with onset of malignant arrhythmias. If alpha-adrenoceptor mechanisms play a significant role in induction of life-threatening arrhythmias, inhibition of these receptors with specific alpha-adrenoceptor antagonists should protect against disturbances in cardiac rhythm. To test this hypothesis, we induced ventricular fibrillation (VF) in 21 mongrel dogs with healed myocardial infarctions (MI) by 2-min coronary artery occlusion during exercise. On a subsequent day, the exercise plus ischemia test was repeated after the alpha 1-adrenoceptor antagonist prazosin HCl (0.5 mg/kg intravenously, i.v.; n = 14) or the alpha 1A-adrenergic receptor subtype antagonist WB4101 (2.0 mg/kg i.v., n = 9). Prazosin elicited a significant reduction in left ventricular systolic pressure (LVSP, control 157.0 +/- 6.5 vs. prazosin 118.5 +/- 2.7 mm Hg) and prevented arrhythmias in 13 of 14 animals (chi square p < 0.001). No other hemodynamic parameters, either before or during the coronary occlusion, were altered by prazosin. WB4101 did not alter any hemodynamic parameters either before or during coronary artery occlusion, yet prevented VF in 7 ...Continue Reading

Citations

Feb 6, 2004·European Journal of Pharmacology·Yong-Fu XiaoAlexander Leaf
Sep 25, 1999·European Journal of Pharmacology·T Obata, Y Yamanaka
Oct 24, 1998·Progress in Biophysics and Molecular Biology·E Carmeliet, K Mubagwa
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Jun 26, 2001·Journal of Autonomic Pharmacology·R Chess-Williams, H L Milton
Jun 21, 2005·Journal of Cardiovascular Pharmacology and Therapeutics·James A Reiffel

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