Search

Equal reductions in heart rate (44 beats X min-1) were obtained in cats by treatment with either the beta blocking agent timolol or alinidine, an agent claimed to cause bradycardia without interfering with beta adrenoceptor function. Infarct size was measured by staining with triphenyltetrazolium-chloride after 5 h of coronary occlusion and related to the area of hypoperfused myocardium as measured by autoradiography. Regional myocardial blood flow was measured by 15 micron radiolabelled microspheres. Compared with the control cats, in whom 87.4 (SEM 2.2)% of hypoperfused myocardium developed into necrosis, timolol reduced infarct size to 65.8 (SEM 2.6)% (p less than 0.001) and alinidine to 76.2 (SEM 3.1)% (p less than 0.01) of the hypoperfused area. Timolol reduced infarct size more than did alinidine (p less than 0.01). Necrosis was more extensive in the endocardium than in the epicardium in all groups. In the subendocardium timolol and alinidine reduced infarct size to the same extent, whereas timolol reduced infarct size more than alinidine in the subepicardium. Although heart rate proved to be the dominant haemodynamic predictor of infarct size, this study indicates that mechanisms other than reduced oxygen demand associated with bradycardia and cardiodepression are operating in the ischaemic myocardium during beta adrenergic blockade.

Distribution of radiolabelled microspheres is widely utilized for determination of regional blood flow in experimental myocardial infarction studies. The purpose of this investigation was evaluation of the microsphere method during 1 h of regional ischaemia. Special attention was focused upon loss of preocclusion microspheres from ischaemic myocardium; mechanisms for loss and blood flow distribution in non-ischaemic left ventricle. Microspheres (15 micron) were injected into the left atrium in nine pentobarbital anaesthetized cats prior to coronary artery occlusion and again after 1 h of occlusion. Preocclusion blood flow estimates were lower in ischaemic compared with non-ischaemic myocardium (1.36 vs. 1.62 cm3 X min-1 X g-1, P = 0.002), corresponding to 16% apparent loss. In endocardial ischaemic tissue, development of oedema could account for the loss. In epicardial ischaemic tissue, oedema was not present and loss was therefore due to migration of microspheres. Epicardial loss increased in proportion to restoration of left ventricular contractility. There was no evidence for significant microsphere loss through lymphatic pathways. In non-ischaemic left ventricular tissue, myocardial blood flow was evenly distributed from apex to base, and also between endocardial and epicardial layers. This study quantitates an important limitation to measurements of local blood flow in ischaemic myocardium by radiolabelled microspheres.

The relationship between myocardial infarct size and loss of 15-micron microspheres from ischaemic tissue was investigated in anaesthetized cats. Radioactive microspheres were injected in the left atrium before and 5 h after left anterior descending coronary artery occlusion. Left ventricular hypoperfused zone (HZ) averaged 36.6% and infarct size (IS) 31.6%. Thus, 86% of HZ evolved into necrosis. Preocclusion blood flow was lower in ischaemic (1.62 ml/min per g) compared with non-ischaemic myocardium (2.09, p = 0.002), indicating 22% microsphere loss. In ischaemic subendocardium, oedema (3.7%) could account for the apparent loss. In ischaemic subepicardium, oedema was less pronounced and 18% physical sphere loss occurred. Subepicardial loss increased in proportion to IS and IS/HZ ratio (r2 = 0.71; p less than 0.005). Non-entrapment of 15-micron spheres in coronary circulation averaged 0.6%, and preocclusion spheres appeared in coronary sinus blood throughout the ischaemic period. In systemic circulation, non-entrapment during injection of preocclusion spheres was 7.8%, but only 1.8% 5 h later. Release of postocclusion spheres took place during KCl injection. Thus, myocardial ischaemia is associated with alterations in microvascular function allowing release of entrapped 15-micron spheres. Also, the magnitude of microsphere loss per gram tissue is related to infarct size.

The fate of 15 micrometers microspheres in ischaemic myocardial tissue was investigated. The spheres were delivered to the left atrium before acute coronary artery ligation. 10 h later the myocardium was examined for its contents of preocclusion spheres, as well as spheres delivered immediately before sacrifice. The ischaemic tissue contained 11 to 60% less preocclusion spheres, compared with nonischaemic tissue in the same hearts. On average, 26% of preocclusion spheres were lost during the 10 h period. Negligible amounts of the lost spheres could be retrieved from cardiac lymph nodes in the mediastinum. Most likely, the spheres migrated through venous pathways; a substantial number of preocclusion spheres were present in the lungs after 10 h, the bulk of which had originated from other organs than the infarct. These results quantify an important limitation to the use of microsphere distribution as a method for tissue blood flow measurements in infarcted myocardium when the period of coronary artery occlusion exceeds a few hours.