Steinberg C, Notterman D A
Division of Pediatric Critical Care Medicine, New York Hospital-Cornell Medical Center, New York 10021, USA.
Crit Care Med. 1996 Dec;24(12):2042-5. doi: 10.1097/00003246-199612000-00018.
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.
Prospective dose-response study.
Animal research laboratory of a university medical center.
Male Sprague-Dawley rats.
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.
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.
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.
确定肌肽（β-丙氨酰组胺）对完整麻醉大鼠模型血流动力学的影响。肌肽在离体灌注豚鼠心脏中已被证明是一种正性肌力药物。
前瞻性剂量反应研究。
大学医学中心的动物研究实验室。
雄性Sprague-Dawley大鼠。
8只雄性Sprague-Dawley大鼠用氯胺酮和咪达唑仑麻醉。插入气管切开管、中心静脉导管和动脉导管。通过右胸切开术在升主动脉周围放置电磁流量探头以测量心输出量。在30秒内静脉注射0至10mg/kg的肌肽剂量，并在基线和效应峰值时测量血流动力学参数。
在3mg/kg和10mg/kg剂量下，肌肽显著降低平均动脉血压、全身血管阻力指数和左心室每搏功指数。肌肽对心率、中心静脉压、心脏指数或每搏指数没有影响。较低剂量的肌肽对测量变量没有影响。
在这个开胸大鼠模型中，肌肽的主要药理作用是全身动脉血管舒张。提示有负性肌力作用。低血压是这些肌肽诱导作用的继发结果。这些结果与先前使用离体豚鼠心脏制剂发表的结果不同。我们的模型表明，为肌肽开发临床应用的努力应利用其血管效应而非心脏效应。物种差异也可能起作用。
