The isolated blood-perfused rat heart: an inappropriate model for the study of ischaemia- and infarction-related ventricular fibrillation.
1. Well-characterized in vivo and in vitro models exist for the study of ischaemia- and infarction-related ventricular fibrillation (VF). In rats in vivo, VF appears to occur in distinct acute ischaemia- (early) and infarction-related (late) phases. Interestingly, isolated buffer-perfused rat hearts do not develop late VF. This raises the possibility that unidentified components of the blood may be responsible for late VF. We thus sought to characterize an isolated blood-perfused rat heart in order to investigate the possible influence of blood components on arrhythmias arising from ischaemia and infarction. 2. Hearts, excised from male Wistar rats, were perfused in the Langendorff mode with blood from support rats (male Wistar, 350-430 g) via an extracorporeal circuit. Perfused hearts underwent left coronary artery occlusion for 240 min or a sham procedure (n=10 group(-1)). 3. Only 10% of ischaemic hearts developed late VF (90-240 min). Tissue myeloperoxidase activity (an index of neutrophil accumulation) increased during ischaemia from 0.017+/-0.004 (six fresh hearts) to 0.056+/-0.005 units mg protein(-1) (P<0.05) at 240 min, but values were similar in sham hearts (0.083+/-0.013). Likewise, the decline (-1 vs 240 min of ischaemia shown) in circulating total white blood cells from 6.8+/-0.5 to 1.9+/-0.2 x 10(3) micro l(-1) and in platelets from 441+/-32 to 274+/-16 x 10(3) micro l(-1) (both P<0.05) was similar in time-matched sham hearts (data not shown). 4 Surprisingly, only 10% of ischaemic hearts developed early VF (0-90 min), although the incidence of early ventricular tachycardia was 100% in these hearts (P<0.05 vs sham hearts). Blood K+ values were normal (hyperkalaemia suppresses VF). 5 Although late VF was absent in blood-perfused hearts, it would be premature to conclude from this that late VF is not mediated by blood components. This is because the similar neutrophil accumulation in ischaemic and sham hearts, the decline in numbers of circulating blood components, and the unexpected paucity of early VF all question the validity of the model.
Clements-Jewery
Hugh
H
Centre for Cardiovascular Biology and Medicine, King's College London, The Rayne Institute, St Thomas' Hospital, Lambeth Palace Road, London SE1 7EH.
Hearse
David J
DJ
Curtis
Michael J
MJ
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology / Q000503:physiopathology; D001794:Blood Pressure / Q000502:physiology; D004562:Electrocardiography; D005780:Gelatin / Q000494:pharmacology; D006321:Heart / Q000187:drug effects / Q000503:physiopathology*; D006339:Heart Rate / Q000502:physiology; D006352:Heart Ventricles / Q000201:enzymology / Q000503:physiopathology; D006439:Hemodynamics / Q000502:physiology; D066298:In Vitro Techniques; D007958:Leukocyte Count; D008297:Male; D009203:Myocardial Infarction / Q000150:complications / Q000473:pathology; D017202:Myocardial Ischemia / Q000150:complications / Q000473:pathology; D010477:Perfusion / Q000379:methods*; D009195:Peroxidase / Q000378:metabolism; D010952:Plasma Substitutes / Q000494:pharmacology; D010976:Platelet Count; D051381:Rats; D017208:Rats, Wistar; D013386:Succinates / Q000494:pharmacology; D014693:Ventricular Fibrillation / Q000097:blood / Q000209:etiology / Q000503:physiopathology
D010952:Plasma Substitutes; D013386:Succinates; C060085:succinylated gelatin; D005780:Gelatin; D009195:Peroxidase