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托哌可卡因对清醒和麻醉兔的心血管作用:缺乏神经-心脏相互作用及急性神经毒性的证据

Cardiovascular effects of tropacocaine in conscious and anesthetized rabbits: lack of evidence for neuro-cardiac interactions and acute neurotoxicity.

作者信息

Rhee H M, Lee S Y, Lee S M, Valentine J L

机构信息

Food and Drug Administration, Division of Metabolism and Endocrine Drug Products, Rockville, Maryland 20857, USA.

出版信息

Neurotoxicology. 1995 Spring;16(1):145-51.

PMID:7603635
Abstract

The cardiovascular effects of tropacocaine, a structural analog of cocaine, were investigated in both conscious and anesthetized New Zealand white rabbits to determine if such effects were mediated through the CNS as had been demonstrated with cocaine, i.e., did a neuro-cardiac pathway exist? To facilitate the requisite cardiovascular measurements in both urethane- and pentobarbital-anesthetized animals, the right femoral artery and vein were cannulated for the measurement of arterial blood pressure and subsequent delivery of drugs, respectively. In addition, urethane-anesthetized animals had a branch of the left renal nerve isolated and multiunit renal nerve activity was monitored to obtain measures of sympathetic nerve activity originating from the CNS. Animals utilized in conscious experiments were surgically prepared 3 days prior to drug administration by placing canulae in the femoral artery and vein that were tunneled subcutaneously to the back between the scapulae. ECG and respiratory activity were also monitored in each animal. Doses of 0.3, 1, 3, and 10 mg/kg of tropacocaine were administered in both an ascending and descending fashion at 15 min intervals to 5 animals in each group, i.e., conscious, urethane-, and pentobarbital-anesthetized. In urethane-anesthetized animals a comparison was made between sympathetic renal nerve activity, systolic and diastolic blood pressure, respiratory rate, and heart rate. No pressor effects were observed and the changes in renal nerve activity could not be assigned as the cause of the observed depressor effects at the higher doses.(ABSTRACT TRUNCATED AT 250 WORDS)

摘要

对可卡因的结构类似物托派可卡因的心血管效应进行了研究,实验对象为清醒和麻醉状态下的新西兰白兔,目的是确定此类效应是否像可卡因那样通过中枢神经系统介导,即是否存在神经 - 心脏通路?为便于在氨基甲酸乙酯和戊巴比妥麻醉的动物身上进行必要的心血管测量,分别将右股动脉和静脉插管,用于测量动脉血压和随后给药。此外,对氨基甲酸乙酯麻醉的动物分离出左肾神经的一个分支,并监测多单位肾神经活动,以获取源自中枢神经系统的交感神经活动指标。清醒实验中使用的动物在给药前3天进行手术准备,通过在股动脉和静脉放置插管,经皮下隧道引至肩胛骨之间的背部。还对每只动物监测心电图和呼吸活动。以15分钟的间隔,按升序和降序方式向每组5只动物(即清醒、氨基甲酸乙酯麻醉和戊巴比妥麻醉的动物)分别给予0.3、1、3和10mg/kg的托派可卡因。在氨基甲酸乙酯麻醉的动物中,对交感肾神经活动、收缩压和舒张压、呼吸频率和心率进行了比较。未观察到升压效应,且在较高剂量下,肾神经活动的变化不能被认定为所观察到的降压效应的原因。(摘要截短为250字)

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