Cocaine enhances myocarditis induced by encephalomyocarditis virus in murine model.
Cocaine enhances myocarditis induced by encephalomyocarditis virus in murine model.
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可卡因增强小鼠模型中脑心肌炎病毒诱导的心肌炎。
DOI：
10.1152/ajpheart.00648.2001
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发表时间：
2002
期刊：
影响因子：
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通讯作者：
Morgan,JamesP
中科院分区：
文献类型：
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作者：
Wang,Ju-Feng;Zhang,Jielin;Min,Jiang-Yong;Sullivan,MatthewF;Crumpacker,ClydeS;Abelmann,WalterH;Morgan,JamesP
本研究旨在探讨可卡因是否会加重病毒性心肌炎并增加其发病率。最近的临床证据表明，可卡因滥用会增加心肌炎的发病率。然而，还没有直接证明可卡因暴露会增加小鼠心肌炎。BALB/c小鼠分为生理盐水对照组、脑心肌炎病毒组（EMCV）、10 mg/kg可卡因（Coc-10）、30 mg/kg可卡因（Coc-30）、50 mg/kg可卡因（Coc-50）、EMCV+Coc-10、EMCV+Coc-30、EMCV+Coc-50 8组。接种EMCV后，小鼠每天服用可卡因或生理盐水，持续90天。小鼠接种EMCV后的不同时间被安乐死。记录死亡率并评估心肌炎严重程度。古柯碱处理心肌炎小鼠的死亡率，分别由22% （EMCV）增加到25.7% （Coc-10+EMCV）、41.4% （Coc-30+EMCV）和51.4% (Coc-50+EMCV) （P< 0.05）。在暴露于可卡因的感染小鼠中，炎症细胞浸润和心肌病变的发生率和严重程度更高。仅在感染前使用可卡因不会加重心肌炎。去甲肾上腺素（NE）测定显示，可卡因暴露显著增加心肌NE浓度，但这种增加在感染动物中被部分抑制。肾上腺切除术消除了可卡因对死亡率的影响。此外，β受体阻滞剂心得安显著降低了可卡因对心肌炎小鼠的增强作用。综上所述，可卡因增加了小鼠病毒性心肌炎的严重程度和死亡率。增加的儿茶酚胺可能是造成这种影响的主要因素。
This study was designed to investigate whether cocaine can exacerbate viral myocarditis and increase its incidence. Recent clinical evidence suggests that cocaine abuse increases the incidence of myocarditis. However, it has not been directly demonstrated that cocaine exposure enhances murine myocarditis. BALB/c mice were divided into eight groups: saline control, encephalomyocarditis virus (EMCV), 10 mg/kg cocaine (Coc-10), 30 mg/kg cocaine (Coc-30), 50 mg/kg cocaine (Coc-50), EMCV+Coc-10, EMCV+Coc-30, EMCV+Coc-50. After inoculation with EMCV, the mice were treated daily with either cocaine or saline for 90 days. Mice were euthanized at different days after EMCV inoculation. Mortality was recorded and myocarditis severity was evaluated. The mortality of the myocarditis mice treated with cocaine increased significantly, from 22% (EMCV) to 25.7% (Coc-10+EMCV), 41.4% (Coc-30+EMCV), and 51.4% (Coc-50+EMCV) (P< 0.05), respectively. The incidence and severity of inflammatory cell infiltration and myocardial lesions was higher in infected mice exposed to cocaine. Cocaine administered only before infection did not exacerbate myocarditis. Norepinephrine (NE) assay showed that cocaine exposure significantly increased myocardial NE concentration but this increase was partially inhibited in infected animals. Adrenalectomy abolished the effect of cocaine on mortality. Furthermore, propranolol, a β-blocker, significantly decreased the enhancing effects of cocaine on myocarditis mice. In conclusion, cocaine increases the severity and mortality of viral myocarditis in mice. Increased catecholamines may be a major factor responsible for this effect.