Independent contribution of catecholamines to arrhythmogenesis during evolving infarction in the isolated rat heart.
Ventricular fibrillation (VF) in conscious rats with coronary artery ligation occurs in two phases, before (phase 1) and after (phase 2) 90 min of ischaemia respectively. The mechanisms of phase 2 VF are not established. Interestingly, phase 2 VF is absent in isolated (denervated) buffer-perfused rat hearts. We investigated whether catecholamine supplementation (to mimic sympathetic drive) was sufficient to restore phase 2 VF in such hearts. Isolated rat hearts (n=10 per group) underwent coronary ligation for 240 min. At 90 min, during a period of relative electrical stability, the perfusion solution was switched from standard (Krebs) to identical solution or Krebs containing catecholamines (313 nM noradrenaline and 75 nM adrenaline) with or without 10 microM trimazosin (an alpha(1)-adrenoceptor antagonist) or 10 microM atenolol (a beta(1)-adrenoceptor antagonist). Although in all groups the incidence of phase 1 VF was high (80 - 100%), the temporal distribution of VF was monophasic, i.e. only one heart in one group developed phase 2 VF (P=NS). Other ventricular arrhythmias (e.g., tachycardia; VT) exhibited a similar temporal distribution. Nevertheless, haemodynamic changes confirmed sympathomimetic effects of catecholamines, e.g., heart rate was increased from 278+/-7 beats min(-1) in controls to 335+/-8 beats min(-1) (P<0.05) by catecholamines, an effect that could be blocked by atenolol (285+/-7 beats min(-1)) but not by trimazosin (342+/-12 beats min(-1)). Coronary flow was correspondingly increased from 7.7+/-0.7 ml min(-1) g(-1) to 16.5+/-1.3 ml min(-1) g(-1) (P<0.05); this effect could be blocked by atenolol (8.1+/-0.6 ml min(-1) g(-1)) and was enhanced by trimazosin (20.7+/-2.4 ml min(-1) g(-1)). In conclusion, despite evidence of adequate alpha- and beta-adrenoceptor activation, catecholamine supplementation to isolated buffer-perfused rat hearts was insufficient to restore phase 2 VF. It therefore appears unlikely that catecholamines alone mediate phase 2 VF.
Clements-Jewery
Hugh
H
The King's Centre for Cardiovascular Biology and Medicine, Cardiovascular Research, The Rayne Institute, St Thomas' Hospital, Lambeth Palace Road, London SE1 7EH.
Hearse
David J
DJ
Curtis
Michael J
MJ
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism*; D002395:Catecholamines / Q000494:pharmacology / Q000502:physiology* / Q000627:therapeutic use; D003326:Coronary Circulation / Q000187:drug effects / Q000502:physiology; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism*; D017202:Myocardial Ischemia / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D013610:Tachycardia / Q000209:etiology / Q000378:metabolism; D014693:Ventricular Fibrillation / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism
D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D002395:Catecholamines