Propranolol ameliorates and epinephrine exacerbates progression of acute and chronic viral myocarditis.
Propranolol ameliorates and epinephrine exacerbates progression of acute and chronic viral myocarditis.
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DOI：
10.1152/ajpheart.00258.2005
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发表时间：
2005-10
期刊：
影响因子：
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通讯作者：
Ju-Feng Wang;A. Meissner;Sohail Malek;Yu Chen;Q. Ke;Jielin Zhang;V. Chu;T. Hampton;C. Crumpacker;W. Abelmann;I. Amende;J. Morgan
中科院分区：
文献类型：
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作者：
Ju-Feng Wang;A. Meissner;Sohail Malek;Yu Chen;Q. Ke;Jielin Zhang;V. Chu;T. Hampton;C. Crumpacker;W. Abelmann;I. Amende;J. Morgan
最近的研究指出心力衰竭中促炎细胞因子和神经体液介质之间的重要相互作用。在这里，我们研究β-肾上腺素能系统对细胞因子和神经体液因子的影响以及病毒性心肌炎的后遗症。在病毒感染的 BALB/c 小鼠实验模型中，我们研究了肾上腺素和普萘洛尔对心肌形态、细胞因子基因表达和存活的急性和慢性影响。 BALB/c小鼠接种脑心肌炎病毒(EMCV)或假接种盐水并随访30天。肾上腺素增加了 EMCV 诱导的炎症细胞浸润和心肌坏死的严重程度。在接种 EMCV 的小鼠中，肾上腺素显着增强了 TNF-α、IL-6 和 IL-10 的基因表达。经肾上腺素治疗的 EMCV 接种小鼠 30 天后的存活率降至 40%，而未治疗的 EMCV 接种小鼠的存活率为 70%（P < 0.05）。使用 β 受体阻滞剂普萘洛尔治疗可显着降低 EMCV 接种小鼠的死亡率、心肌坏死和炎症细胞浸润。普萘洛尔还抑制 TNF-α、IL-6 和 IL-10 的基因表达。接种 EMCV 120 天后单剂量肾上腺素导致 70% 的感染小鼠猝死；普萘洛尔使死亡发生率显着降低至 33%。这些结果表明病毒性心肌炎的急性和慢性阶段受到β-肾上腺素能系统及其与促炎细胞因子的相互作用的调节。
Recent studies point to important interactions between proinflammatory cytokines and neurohumoral mediators in heart failure. Here we investigate the influence of the beta-adrenergic system on cytokines and neurohumoral factors and the sequelae of viral myocarditis. In an experimental model with virus-infected BALB/c mice, we studied the acute and chronic effects of epinephrine and propranolol on myocardial morphology, cytokine gene expression, and survival. BALB/c mice were inoculated with the encephalomyocarditis virus (EMCV) or sham inoculated with saline and followed for 30 days. Epinephrine increased the severity of inflammatory cell infiltration and myocardial necrosis induced by EMCV. Gene expression of TNF-alpha, IL-6, and IL-10 was markedly enhanced by epinephrine in EMCV-inoculated mice. Survival rate after 30 days was reduced to 40% in epinephrine-treated EMCV-inoculated mice compared with 70% in untreated EMCV-inoculated mice (P < 0.05). Treatment with the beta-blocker propranolol significantly decreased mortality, myocardial necrosis, and infiltration of inflammatory cells in EMCV-inoculated mice. Propranolol also suppressed gene expression of TNF-alpha, IL-6, and IL-10. A single dose of epinephrine 120 days after EMCV inoculation caused sudden death in 70% of infected mice; propranolol significantly reduced incidence of death to 33%. These results indicate that acute and chronic stages of viral myocarditis are modulated by the beta-adrenergic system and its interactions with proinflammatory cytokines.