Acute and chronic observations of complete atrioventricular block in rats

Abstract

The mechanisms of production, and gross, microscopic and electrocardiograhic findings of surgically-induced complete heart block (CHB) in the adult rat are presented. This is an effective in vivo model for establishing alternative methods to electronic pacemakers and for providing detailed information aimed at replacement, reduction and refinement of the technique. Sternal thoracotomy was employed to identify the epicardial fat pad by the aortic root, used as a landmark for cauterization of the atrioventricular (AV) node. Stable CHB was produced in 60 rats with a 70% survival rate. The best survival rate was observed in 8-week-old animals weighing 221±27.6 g. Heart rate before cauterization was 387±55 bpm, reduced after cauterization to 126±40 bpm in the survival and to 65±19 bpm in the non-survival groups. At 30 days findings were: elevated left ventricular end-diastolic pressure (21±5.4 mmHg, P<0.05); maximal rate of rise of left ventricular pressure (LVP) during isovolumetric contraction (2192±235 mmHg/s, P<0.05); maximal rate of decrease of LVP (-1658±191 mmHg/s, P<0.05); isovolumetric relaxation constant (5.7±0.8 ms, P<0.05) with wet-to-dry lung–weight ratio (78.1±0.4, P<0.05); heart weight/body weight (0.6±0.1, P<0.05); heart volume (1.8±0.3 mL, P<0.05); longitudinal diameter (20.2±1.91 mm, P<0.05); and transversal diameter (17.0±1.4 mm, P<0.05) with supported dilated cardiomyopathy which culminated in chronic heart failure. CHB hearts had increased preload and replacement of myofibrils by collagen. CHB was achieved reproducibly by cauterization of the rat AV node and/or His bundle. This led to electrophysiological, hemodynamic, and structural remodeling, and could be useful in long-term cardiac remodeling assessments and potential therapy development.