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在大鼠中,去甲肾上腺素因儿茶酚胺过量导致的心肺毒性比肾上腺素更多。

Norepinephrine Leads to More Cardiopulmonary Toxicities than Epinephrine by Catecholamine Overdose in Rats.

作者信息

Lu Wen-Hsien, Chen Hsin-Hung, Chen Bo-Hau, Lee Jui-Chen, Lai Chi-Cheng, Li Che-Hsing, Tseng Ching-Jiunn

机构信息

Department of Pediatrics, Kaohsiung Veterans General Hospital, Kaohsiung 813, Taiwan.

School of Medicine, National Yang-Ming University, Taipei 112, Taiwan.

出版信息

Toxics. 2020 Sep 16;8(3):69. doi: 10.3390/toxics8030069.

Abstract

While catecholamines like epinephrine (E) and norepinephrine (NE) are commonly used in emergency medicine, limited studies have discussed the harm of exogenously induced catecholamine overdose. We investigated the possible toxic effects of excessive catecholamine administration on cardiopulmonary function and structure via continuous 6 h intravenous injection of E and/or NE in rats. Heart rate, echocardiography, and ventricular pressure were measured throughout administration. Cardiopulmonary structure was also assessed by examining heart and lung tissue. Consecutive catecholamine injections induced severe tachycardia. Echocardiography results showed NE caused worse dysfunction than E. Simultaneously, both E and NE led to higher expression of Troponin T and connexin43 in the whole ventricles, which increased further with E+NE administration. The NE and E+NE groups showed severe pulmonary edema while all catecholamine-administering groups demonstrated reduced expression of receptor for advanced glycation end products and increased connexin43 levels in lung tissue. The right ventricle was more vulnerable to catecholamine overdose than the left. Rats injected with NE had a lower survival rate than those injected with E within 6 h. Catecholamine overdose induces acute lung injuries and ventricular cardiomyopathy, and E+NE is associated with a more severe outcome. The similarities of the results between the NE and E+NE groups may indicate a predominant role of NE in determining the overall cardiopulmonary damage. The results provide important clinical insights into the pathogenesis of catecholamine storm.

摘要

虽然肾上腺素(E)和去甲肾上腺素(NE)等儿茶酚胺类药物在急诊医学中常用,但关于外源性儿茶酚胺过量危害的研究有限。我们通过在大鼠中连续6小时静脉注射E和/或NE,研究了过量给予儿茶酚胺对心肺功能和结构的潜在毒性作用。在给药过程中测量心率、超声心动图和心室压力。还通过检查心脏和肺组织来评估心肺结构。连续注射儿茶酚胺导致严重心动过速。超声心动图结果显示,NE引起的功能障碍比E更严重。同时,E和NE均导致整个心室肌钙蛋白T和连接蛋白43表达升高,联合给予E+NE时进一步升高。NE组和E+NE组出现严重肺水肿,而所有给予儿茶酚胺的组肺组织中晚期糖基化终产物受体表达降低,连接蛋白43水平升高。右心室比左心室更容易受到儿茶酚胺过量的影响。注射NE的大鼠在6小时内的存活率低于注射E的大鼠。儿茶酚胺过量可诱发急性肺损伤和心室心肌病,E+NE与更严重的后果相关。NE组和E+NE组结果的相似性可能表明NE在决定整体心肺损伤方面起主要作用。这些结果为儿茶酚胺风暴的发病机制提供了重要的临床见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5502/7560392/f473aa1d74f0/toxics-08-00069-g001.jpg

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