CARDIAC-FAILURE IN ISOLATED WORKING RAT-HEART - EFFECT OF CICLETANINE

Background: The aim of this study was to introduce a simple experimental model for evaluation of drug action on cardiac functional capacity after development of myocardial infarction and to assess the effect of cicletanine, a furopyridine antihypertensive drug with cardioprotective properties. Methods: The effect of cicletanine gavaged for 2 weeks at a 30-mg/kg daily dose on cardiac functional parameters in working hearts isolated from rats subjected to permanent ligation of the left anterior descending coronary artery was studied. Coronary artery ligation was performed under anesthesia at the 7th day of treatment. One day after termination of treatment, hearts were isolated in a ''working'' mode, and aortic flow (AF), left ventricular developed pressure (LVDP), its first derivative (+dP/dt(max)), and left ventricular end-diastolic pressure (LVEDP) were monitored at different preload and afterload pressures. Results: Aortic flow, LVDP, and +dP/dt(max) were significantly lower and LVEDP was higher in vehicle-treated infarcted hearts as compared with hearts isolated from sham-operated rats, which did not undergo coronary ligation and were treated with the vehicle 1% methylcellulose suspension. Cicletanine significantly improved AF, LVDP, +dP/dt(max), and LVEDP; however, it did not influence heart rate and coronary flow. The drug decreased the number of premature ventricular contractions as compared with vehicle-treated infarcted hearts. Infarcted hearts of cicletanine-treated rats exhibited higher ability to adapt to increasing preload and afterload than did vehicle-treated infarcted hearts. Conclusions: The results presented here show the usefulness of this simple model of in vivo infarcted, isolated working heart to evaluate drug action in left ventricular dysfunction after coronary artery occlusion in rats. The beneficial effect of cicletanine suggests that this drug is a favorable therapeutic option in alleviating left ventricular dysfunction developed after myocardial infarction.