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Complex adrenergic and inflammatory mechanisms contribute to phase 2 ventricular arrhythmias in anaesthetized rats
Author(s) -
ClementsJewery Hugh,
Andrag Ellen,
Hearse David J,
Curtis Michael J
Publication year - 2009
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.2008.00054.x
Subject(s) - atenolol , prazosin , medicine , ventricular fibrillation , ventricular tachycardia , cardiology , heart rate , tachycardia , myocardial infarction , anesthesia , blood pressure , receptor , antagonist
Mandarin translation of abstract Background and purpose: The mechanisms responsible for phase 2 (infarct‐related) ventricular arrhythmias remain unclear. We have investigated the role of α 1 and β 1 adrenoceptor activation and the interaction of this with infarct neutrophil accumulation, in anaesthetized rats. Experimental approach: Neutrophil‐replete Sprague‐Dawley rats ( n = 8–9 per group) were anaesthetized and randomized to receive vehicle, prazosin (0.5 mg·kg −1 i.v.), atenolol (4 mg·kg −1 i.v.) or their combination prior to left main coronary artery occlusion. A further group was depleted of neutrophils and received both atenolol and prazosin. Coronary ligation in all groups was maintained for 240 min. Key results: Atenolol and prazosin treatment lowered heart rates and blood pressures respectively, but neither agent given alone affected the incidence of phase 2 ventricular tachycardia or fibrillation. However, co‐administration of atenolol with prazosin reduced phase 2 ventricular premature beats (log 10 ‐transformed totals were 1.25 ± 0.26 vs. 2.43 ± 0.18 in controls; P < 0.05). Neutrophil depletion attenuated this antiarrhythmic effect (log 10 ‐transformed total ventricular premature beats were 1.66 ± 0.35; P > 0.05 vs. controls). Conclusions and implications: Phase 2 arrhythmias appear to depend in part on a complex interaction between catecholamines and neutrophils. A model of this interaction is proposed. Mandarin translation of abstract