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

Background: The aim of this study was to introduce a simple experiment al 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 cardioprotecti ve properties. Methods: The effect of cicletanine gavaged for 2 weeks at a 30-mg/kg daily dose on cardiac functional parameters in working h earts isolated from rats subjected to permanent ligation of the left a nterior descending coronary artery was studied. Coronary artery ligati on 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-diasto lic pressure (LVEDP) were monitored at different preload and afterload pressures. Results: Aortic flow, LVDP, and +dP/dt(max) were significa ntly 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% methylc ellulose suspension. Cicletanine significantly improved AF, LVDP, +dP/ dt(max), and LVEDP; however, it did not influence heart rate and coron ary flow. The drug decreased the number of premature ventricular contr actions as compared with vehicle-treated infarcted hearts. Infarcted h earts of cicletanine-treated rats exhibited higher ability to adapt to increasing preload and afterload than did vehicle-treated infarcted h earts. Conclusions: The results presented here show the usefulness of this simple model of in vivo infarcted, isolated working heart to eval uate 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 ventr icular dysfunction developed after myocardial infarction.