Hemodynamic effects of carcinine in the anesthetized, instrumented, open-chest rat

Objective: To determine the pharmacologic effect of carcinine (β- alanyl histamine), a compound that has been shown to be a positive inotrope in the isolated perfused guinea pig heart, on hemodynamics in an intact, 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 tracheostomy tube, and central venous and arterial catheters were inserted. An electromagnetic flow probe was placed around the ascending aorta through a right thoracotomy for measurement of cardiac output. Dosages of carcinine from 0 to 10 mg/kg were infused intravenously over 30 secs, and hemodynamic parameters were measured at baseline and at peak effect. Measurements and Main Results: At dosages of 3 mg/kg and 10 mg/kg, carcinine significantly reduced mean arterial blood pressure, systemic vascular resistance index, and left ventricular stroke work index. There was no carcinine-induced effect on heart rate, central venous pressure, cardiac index, or stroke index. Lower doses of carcinine had no effect on the measured variables. Conclusions: In this open-chest rat model, the primary pharmacologic effect of carcinine is systemic arterial 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 role for carcinine should exploit vascular rather than cardiac effects. Species differences may also play a role.