AN IN-VITRO METHOD FOR THE EVALUATION OF ANTIARRHYTHMIC AND ANTIISCHEMIC AGENTS BY USING PROGRAMMED ELECTRICAL-STIMULATION OF RABBIT HEART

A new model using isolated rabbit hearts perfused at constant flow in the Langendorff mode with the sinus node destroyed and under constant (2 Hz) pacing is described. Ventricular ischemia (24 min) was induced by ligation of the left ventricular branch of the coronary artery (LVB ), followed by reperfusion (15 min). The programmed electrical stimula tion (PES) technique was used to induce arrhythmias in the ischemic zo ne (IZ). Three agents with different mechanisms of action were tested to validate this model: dl-sotalol (10(-6) and 10(-5) M), oxfenicine ( 10(-6) M), and lidocaine (10(-5) M). These compounds were administered 15 min before the ligature and maintained until the end of the experi ment. Ventricular effective refractory period (VERP), PES-induced vent ricular fibrillation (VF), and coronary perfusion pressure (CPP) were monitored. PES-induced VF was only observed in ischemic tissue. Sotalo l slightly reduced VF incidence only during reperfusion. Oxfenicine pr evented PES-induced VF during the ischemia, but not during reperfusion , while lidocaine prevented VF during ischemia and throughout the repe rfusion period. In conclusion, the rabbit heart model where PES is app lied to normal and ischemic myocardium, appears useful to discern diff erent mechanisms involved in ventricular arrhythmias. In addition, thi s model is considerably cheaper than equivalent dog models.