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1,1 - 二氟乙烷因电解质失衡和心肌细胞损伤导致的心脏毒性(致心律失常)作用

Cardiotoxic (Arrhythmogenic) Effects of 1,1-Difluoroethane Due to Electrolyte Imbalance and Cardiomyocyte Damage.

作者信息

Joshi Kaushal, Barletta Michael, Wurpel John

机构信息

From the St. John's University, Queens, NY.

出版信息

Am J Forensic Med Pathol. 2017 Jun;38(2):115-125. doi: 10.1097/PAF.0000000000000262.

DOI:10.1097/PAF.0000000000000262
PMID:28263233
Abstract

Inhalant abuse is the intentional inhalation of chemical vapors to attain euphoric effects. Many common household products are abused by inhalation and one is 1,1-difluoroethane (DFE), which is a halogenated hydrocarbon used in refrigeration, dust-off spray, and airbrush painting. Although many human DFE abuse cases have been studied, the etiology and mechanism of sudden death is still unknown. In this study, an animal model was used to simulate the human conditions of DFE inhalation abuse that results in sudden death.Current research targets mechanistic studies involving electrolyte changes and cardiomyocyte damage after DFE administration in vivo. To investigate these changes, Sprague Dawley rats (N = 6) were exposed to 30 seconds of 20 L/min of DFE in multiple doses. Isoflurane acted as a control. Two additional groups, epinephrine and epinephrine + DFE, were included to simulate the clinical condition of DFE abuse. Plasma sodium, potassium, calcium, and magnesium levels were measured, followed by lactate dehydrogenase, creatine kinase, and cardiac troponin I levels. In addition, oxidative stress markers were also evaluated in all animal groups. Electrolyte levels showed a significant rise in plasma potassium and magnesium levels for the treated groups. In addition, lactate dehydrogenase, creatine kinase, and cardiac troponin I levels in DFE and epinephrine + DFE administered rats were significantly elevated as compared with control. Some oxidative stress makers were also elevated significantly in treatment groups. Furthermore, histopathological analysis showed hyperemia/congestion in treated rats.These results support cardiotoxic effects indicating that DFE results in fatal arrhythmias, and the study can be important during clinical cases involving inhalant abuse.

摘要

吸入性药物滥用是指故意吸入化学蒸汽以获得欣快感。许多常见的家用产品都被用于吸入性滥用,其中一种是1,1 - 二氟乙烷(DFE),它是一种卤代烃,用于制冷、除尘喷雾和气刷喷漆。尽管已经对许多人类DFE滥用病例进行了研究,但猝死的病因和机制仍然未知。在本研究中,使用动物模型来模拟导致猝死的人类DFE吸入性滥用情况。目前的研究目标是对体内给予DFE后涉及电解质变化和心肌细胞损伤的机制进行研究。为了研究这些变化,将6只Sprague Dawley大鼠暴露于多剂量的20升/分钟的DFE中30秒。异氟烷作为对照。另外纳入肾上腺素组和肾上腺素 + DFE组以模拟DFE滥用的临床情况。测量血浆钠、钾、钙和镁水平,随后测量乳酸脱氢酶、肌酸激酶和心肌肌钙蛋白I水平。此外,还对所有动物组的氧化应激标志物进行了评估。治疗组的电解质水平显示血浆钾和镁水平显著升高。此外,与对照组相比,给予DFE和肾上腺素 + DFE的大鼠的乳酸脱氢酶、肌酸激酶和心肌肌钙蛋白I水平显著升高。治疗组中的一些氧化应激标志物也显著升高。此外,组织病理学分析显示治疗组大鼠有充血/淤血。这些结果支持了心脏毒性作用,表明DFE会导致致命性心律失常,并且该研究在涉及吸入性药物滥用的临床病例中可能具有重要意义。

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