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


METHODS
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.


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
Phase 2 arrhythmias appear to depend in part on a complex interaction between catecholamines and neutrophils. A model of this interaction is proposed.
Clements-Jewery
Hugh
H
The Rayne Institute, St Thomas' Hospital, London, UK.
Andrag
Ellen
E
Hearse
David J
DJ
Curtis
Michael J
MJ
D000317:Adrenergic alpha-Antagonists / Q000008:administration & dosage / Q000627:therapeutic use; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000627:therapeutic use; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000188:drug therapy / Q000209:etiology* / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D001262:Atenolol / Q000008:administration & dosage / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D002395:Catecholamines / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D004562:Electrocardiography; D006339:Heart Rate / Q000187:drug effects; D007958:Leukocyte Count; D008297:Male; D020556:Neutrophil Infiltration / Q000187:drug effects* / Q000276:immunology; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects; D011224:Prazosin / Q000008:administration & dosage / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D011941:Receptors, Adrenergic / Q000378:metabolism*
D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D002395:Catecholamines; D011941:Receptors, Adrenergic; D001262:Atenolol; D011224:Prazosin