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

Article date: February 2009

By: Hugh Clements‐Jewery, Ellen Andrag, David J Hearse, Michael J Curtis in Volume 156, Issue 3, pages 444-453

Background and purpose:  The mechanisms responsible for phase 2 (infarct‐related) ventricular arrhythmias remain unclear. We have investigated the role of α1 and β1 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 (log10‐transformed totals were 1.25 ± 0.26 vs. 2.43 ± 0.18 in controls; P < 0.05). Neutrophil depletion attenuated this antiarrhythmic effect (log10‐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

DOI: 10.1111/j.1476-5381.2008.00054.x

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