ANTIARRHYTHMIC AND HEMODYNAMIC-EFFECTS OF TROPISETRON IN ANESTHETIZEDRABBITS

Tropisetron (ICS 205-930) is a novel drug that blocks serotonin (5-HT3 ) receptors and, at higher concentrations, potassium channels. Program med electrical stimulation (PES) and tracer microspheres were used to investigate antiarrhythmic, systemic, and regional hemodynamic effects in anesthetized rabbits. Tropisetron (0.3, 1, and 3 mg/kg intravenous ly, i.v.) dose-dependently increased the effective refractory period ( ERP) to a first and similarly to a second extrastimulus. The arrhythmi as elicited by PES with one and two extrastimuli were suppressed dose dependently. The same doses and a higher dose (6 mg/kg i.v.) were test ed for systemic, especially cardiodepressant, and regional hemodynamic activity in a second series of experiments. Doses less-than-or-equal- to 3 mg/kg were almost devoid of systemic hemodynamic activity and did not alter the ECG. At the highest dose used (6 mg/kg), cardiodepressi on caused a decrease in blood pressure (BP), cardiac output (CO), and heart rate (HR) and an increase in central venous pressure (CVP). A se lective increase in gastric blood flow was observed, starting at the l owest dose used. The highest cardiodepressant dose reversed this incre ase and decreased regional myocardial blood flow, especially to the su bendocardial layer of the left ventricle, probably by lowering myocard ial oxygen consumption. Antiarrhythmic effects thus start at 0.3 mg/kg , and doses less-than-or-equal-to 3 mg/kg i.v. did not elicit hemodyna mic side effects.