Lee J C, Sponenberg D P
Am J Pathol. 1985 Nov;121(2):316-21.
This study practically delineated the contribution of alpha-adrenoceptor activation to the pathogenesis of norepinephrine (NE) cardiomyopathy. A total of 64 adult New Zealand white rabbits were used. NE cardiomyopathy was produced in rabbits by a 90-minute intravenous infusion of norepinephrine (2 micrograms/kg/min at infusion rate 0.382 ml/min). Arterial blood pressure and heart rate were constantly monitored. Arterial blood samples were obtained at 30-minute intervals for measurements of pH, blood gases, and glucose. Alpha-adrenoceptor blocking agents, when employed, were given 15 minutes prior to the initiation of NE infusion. Two days after treatment the rabbits were killed. The hearts were examined microscopically and assigned a histologic score. Pretreatment with the alpha 1-adrenoceptor blocker prazosin at 50, 100, or 200 micrograms/kg significantly reduced NE-induced myocardial injury in a dose-related manner. In contrast, the presence of alpha 2-adrenoceptor blocker yohimbine at 2.5 or 5.0 mg/kg was ineffective in preventing the formation of myocardial lesions. These findings suggest that NE cardiomyopathy may result largely from activation of the alpha 1-adrenoceptor system in the rabbit model.
本研究切实阐明了α-肾上腺素能受体激活在去甲肾上腺素（NE）心肌病发病机制中的作用。共使用了64只成年新西兰白兔。通过静脉输注去甲肾上腺素90分钟（输注速率为0.382 ml/min，剂量为2微克/千克/分钟）在兔身上诱发NE心肌病。持续监测动脉血压和心率。每隔30分钟采集动脉血样本，用于测量pH值、血气和葡萄糖。使用α-肾上腺素能受体阻断剂时，在开始输注NE前15分钟给药。治疗两天后处死兔子。对心脏进行显微镜检查并给予组织学评分。以50、100或200微克/千克的剂量用α1-肾上腺素能受体阻断剂哌唑嗪预处理，可显著减轻NE诱导的心肌损伤，且呈剂量相关。相比之下，2.5或5.0毫克/千克的α2-肾上腺素能受体阻断剂育亨宾对预防心肌损伤的形成无效。这些发现表明，在兔模型中，NE心肌病可能主要是由α1-肾上腺素能受体系统的激活所致。
