Therapy with cyclosporine in experimental murine myocarditis with encephalomyocarditis virus.
Therapy with cyclosporine in experimental murine myocarditis with encephalomyocarditis virus.
复制标题
环孢素治疗脑心肌炎病毒引起的实验性小鼠心肌炎。
DOI：
10.1161/01.cir.73.5.1058
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发表时间：
1986
期刊：
影响因子：
37.8
通讯作者：
Abelmann,WH
中科院分区：
文献类型：
--
作者：
Monrad,ES;Matsumori,A;Murphy,JC;Fox,JG;Crumpacker,CS;Abelmann,WH
为了解释从感染性病毒性心肌炎到充血性心肌病的进展，提出了一种感染/免疫假说，认为最初的病毒过程激发了对心肌的过度或紊乱的免疫反应。为了测试一种形式的免疫抑制疗法是否可以改善这一过程，我们在感染性心肌炎(脑心肌炎[EMC]病毒)的小鼠制剂中使用了环孢菌素，这种病毒已被证明会导致与人类相似的充血性心肌病。将8周龄雄性DBA-2小鼠感染EMC病毒，随机分为治疗组和对照组。环孢素(25 mg/kg/d)皮下注射3周，从感染后1周病毒复制开始，和(2)感染后3周病毒复制活跃后开始。在病毒复制期间接受治疗的小鼠的死亡率显著高于对照组小鼠(15/21比9/29，p=0.01)。与对照组相比，治疗组的心肌病理(炎症、坏死或钙化)没有明显减轻。在病毒复制期后接受治疗的小鼠，死亡率(8/22vs2/19，NS)与对照组相比没有改善。经治疗的小鼠心肌组织病理损害未见减少。此外，与对照组相比，治疗组小鼠的心脏重量/体重比(1.3+/-0.4%比1.0+/-0.3%，p<0.005)、肺重量/体重比(1.1+/-0.5%比0.8+/-0.3%，p<0.05)和肝脏重量/体重比(6.0+/-0.8%比5.4+/-0.6%，p<0.005)显著增加，这意味着更严重的心肌衰竭。
To explain the progression from infectious viral myocarditis to congestive cardiomyopathy an infection/immune hypothesis has been proposed stating that the primary viral process incites an excessive or disordered immunologic response against the myocardium. To test whether one form of immunosuppressive therapy might ameliorate this process, we used cyclosporine in a murine preparation of infectious myocarditis (encephalomyocarditis [EMC] virus), which has been shown to result in a congestive cardiomyopathy pathologically similar to that seen in man. Eight-week-old male DBA-2 mice were infected with EMC virus and randomized to a treatment or control group. Cyclosporine (25 mg/kg/day) was administered subcutaneously for 3 weeks, starting (1) at 1 week after infection during viral replication, and (2) at 3 weeks after infection, after the period of active viral replication. In mice treated during viral replication there was a significantly higher mortality rate compared with that of control mice (15/21 vs 9/29, p = .01). There was no evident reduction in myocardial pathology (inflammation, necrosis, or calcification) in the treated compared with the control groups. In mice treated after the period of viral replication, there was no improvement in mortality (8/22 vs 2/19, NS) compared with control. Treated mice showed no reduction in myocardial histopathologic lesions. Furthermore, treated mice had significantly greater heart weight/body weight ratios (1.3 +/- 0.4% vs 1.0 +/- 0.3%, p less than .005), lung weight/body weight ratios (1.1 +/- 0.5% vs 0.8 +/- 0.3%, p less than .05), and liver weight/body weight ratios (6.0 +/- 0.8% vs 5.4 +/- 0.6%, p less than .005) than control mice, suggesting more severe myocardial failure.(ABSTRACT TRUNCATED AT 250 WORDS)