Document Detail


K+ channel blockade in the prevention of ventricular fibrillation in dogs with acute ischemia and enhanced sympathetic activity.
MedLine Citation:
PMID:  8606519     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The value of K+ channel blockade in preventing lethal arrhythmias, and specifically those triggered by acute myocardial ischemia and sympathetic hyperactivity, remains unproven. To address this issue, we tested the antifibrillatory effect of d-sotalol, and Ikr blocker, d,l-sotalol, its racemic compound which blocks Ikr, and beta-adrenoreceptors, and propranolol. Ten dogs with a healed anterior myocardial infarction (MI) had ventricular fibrillation (VF) during a 2-min occlusion of the circumflex coronary artery performed toward the end of a submaximal exercise stress test. In successive trials in the same animals, d-sotalol (three injections of 8 mg/kg, one every 12 h), d,l-sotalol (8 mg/kg), and propranolol (1 mg/kg) were tested. All three interventions significantly reduced heart rate (HR) response to exercise, but only d,l-sotalol and propranolol also blunted the reflex HR increase during acute myocardial ischemia. With d-sotalol, HR at 30 s of coronary occlusion was similar (253 +/- 28 beats/min) to that observed in the control tests (259 +/- 35 beats/min). d-Sotalol prevented recurrence of VF in only 1 of 10 dogs tested. One dog was lost to the continuation of the study after occurrence of VF with d-sotalol. Six of 9 dogs (67%) tested with d,l-sotalol and 5 (56%) of the same 9 dogs tested with propranolol were protected from VF. d-Sotalol does not reduce risk of VF during acute myocardial ischemia associated with sympathetic hyperactivity, and lethal events can be prevented by antiadrenergic interventions.
Authors:
E Vanoli; S S Hull; P B Adamson; R D Foreman; P J Schwartz
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of cardiovascular pharmacology     Volume:  26     ISSN:  0160-2446     ISO Abbreviation:  J. Cardiovasc. Pharmacol.     Publication Date:  1995 Dec 
Date Detail:
Created Date:  1996-05-23     Completed Date:  1996-05-23     Revised Date:  2003-11-14    
Medline Journal Info:
Nlm Unique ID:  7902492     Medline TA:  J Cardiovasc Pharmacol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  847-54     Citation Subset:  IM    
Affiliation:
Istituto di Clinica Medica Generale e Terapia Medica, Università di Milano, Italy.
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MeSH Terms
Descriptor/Qualifier:
Animals
Anti-Arrhythmia Agents / pharmacology*
Blood Pressure / drug effects
Dogs
Electrocardiography
Heart Rate / drug effects
Myocardial Ischemia / complications*,  physiopathology
Potassium Channel Blockers*
Propranolol / pharmacology
Sotalol / pharmacology*
Stereoisomerism
Sympathetic Nervous System / drug effects*,  physiopathology
Ventricular Fibrillation / prevention & control*
Chemical
Reg. No./Substance:
0/Anti-Arrhythmia Agents; 0/Potassium Channel Blockers; 3930-20-9/Sotalol; 525-66-6/Propranolol

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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