Literature DB >> 19154442

Complex adrenergic and inflammatory mechanisms contribute to phase 2 ventricular arrhythmias in anaesthetized rats.

Hugh Clements-Jewery1, Ellen Andrag, David J Hearse, Michael J Curtis.   

Abstract

BACKGROUND AND
PURPOSE: The mechanisms responsible for phase 2 (infarct-related) ventricular arrhythmias remain unclear. We have investigated the role of alpha(1) and beta(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.

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Year:  2009        PMID: 19154442      PMCID: PMC2697680          DOI: 10.1111/j.1476-5381.2008.00054.x

Source DB:  PubMed          Journal:  Br J Pharmacol        ISSN: 0007-1188            Impact factor:   8.739


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