Changes in cardiac output, hepatic and renal functions in rats with isoprenaline-induced heart damage

A model of acute rat heart damage by a large single dose of isoprenaline (ISO) (100 mg.kg-1 s.c.) was assessed for its suitability to evaluate changes in drug kinetics in acute heart failure. Within 24h after the administration of the above dose the colorimetric dilution method revealed a decrease in cardiac output by more than 20% and mild increase in total peripheral resistance in anaesthetized female Wistar rats. At the same time, marked hypotension developed with a decrease in mean arterial blood pressure by nearly 20%. An acceleration of both depolarization and repolarization of the atrial and ventricular musculatures and a surprising bradycardia were demonstrated electrocardiographically. ECG failed to demonstrate any signs of myocardial ischaemia. Determination of bromsulphalein and inulin clearance values revealed decreased liver and kidney function. Mild anaesthesia-induced respiratory and metabolic acidosis was improved by ISO administration. The described model at least partially corresponds to the manifestations of acute heart failure with hypotension in man.