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Hemodynamic effects of carcinine in the anesthetized, instrumented, open-chest rat
1Division of Pediatric Critical Care Medicine, New York Hospital-Cornell Medical Center, New York 10021, USA.
Objective:
To determine the pharmacologic effect of carcinine (beta-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.