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


METHODS
Prospective dose-response study.


METHODS
Animal research laboratory of a university medical center.


METHODS
Male Sprague-Dawley rats.


METHODS
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.


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.
Steinberg
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Division of Pediatric Critical Care Medicine, New York Hospital-Cornell Medical Center, New York 10021, USA.
Notterman
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DA
D000758:Anesthesia; D000778:Anesthetics, Dissociative; D000818:Animals; D002336:Carnosine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006439:Hemodynamics / Q000187:drug effects*; D007275:Injections, Intravenous; D007649:Ketamine; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D000778:Anesthetics, Dissociative; D007649:Ketamine; D002336:Carnosine; C015055:carcinine