HEMODYNAMIC-EFFECTS OF CARCININE IN THE ANESTHETIZED, INSTRUMENTED, OPEN-CHEST RAT

Objective: To determine the pharmacologic effect of carcinine (beta-al anyl histamine), a compound that has been shown to be a positive inotr ope in the isolated perfused guinea pig heart, on hemodynamics in an i ntact, anesthetized rat model. Design: Prospective dose-response study . Setting: Animal research laboratory of a university medical center. Subjects: Male Sprague-Dawley rats. Interventions: Eight male Sprague- Dawley rats were anesthetized with ketamine and midazolam. A tracheost omy tube, and central venous and arterial catheters were inserted. An electromagnetic flow probe was placed around the ascending aorta throu gh a right thoracotomy for measurement of cardiac output. Dosages of c arcinine from 0 to 10 mg/kg were infused intravenously over 30 sees, a nd hemodynamic parameters were measured at baseline and at peak effect . Measurements and Main Results: At dosages of 3 mg/kg and 10 mg/kg, c arcinine significantly reduced mean arterial blood pressure, systemic vascular resistance index, and left ventricular stroke work index. The re was no carcinine-induced effect on heart rate, central venous press ure, cardiac index, or stroke index. Lower doses of carcinine had no e ffect on the measured variables. Conclusions: In this open chest rat m odel, the primary pharmacologic effect of carcinine is systemic arteri al vasodilation. A negative inotropic effect is suggested. Hypotension is secondary to these carcinine induced actions. These results differ from results previously published using an isolated guinea pig heart preparation. Our model suggests that efforts to develop a clinical rol e for carcinine should exploit Vascular rather than cardiac effects. S pecies differences may also play a role.