Matsui S, Matsumori A, Matoba Y, Uchida A, Sasayama S
Department of Internal Medicine, Kyoto University Hospital, Japan.
J Clin Invest. 1994 Sep;94(3):1212-7. doi: 10.1172/JCI117438.
Controversy still exists concerning the therapy for viral myocarditis which manifests a wide variety of clinical symptoms. Vesnarinone, a quinolinone derivative that was developed as a positive inotropic agent with complex actions, including phosphodiesterase inhibition and cation channel modification, has recently been confirmed to improve the prognosis of patients with chronic heart failure. However, the precise mechanism of this beneficial effect is not yet clearly understood. In this study, using a murine model of acute viral myocarditis resulting from encephalomyocarditis virus infection, survival and myocardial damage were markedly improved by treatment with vesnarinone. In contrast, survival was not improved by treatment with amrinone, a phosphodiesterase inhibitor. Although vesnarinone did not inhibit viral replication or protect myocytes from viral direct cell injury, it did inhibit the increase in natural killer cell activity after viral infection. On the other hand, amrinone failed to inhibit natural killer cell activity. Both vesnarinone and amrinone suppressed the production of tumor necrosis factor-alpha. Therefore, we postulate that vesnarinone exerted its beneficial effects through an inhibition of natural killer cell activity, and that it serves as an immunomodulator providing new therapeutic possibilities for the treatment of viral myocarditis and/or immunological disorders.
关于表现出多种临床症状的病毒性心肌炎的治疗，目前仍存在争议。维司力农是一种喹啉酮衍生物，最初作为具有复杂作用的正性肌力药物开发，包括磷酸二酯酶抑制和阳离子通道修饰，最近已被证实可改善慢性心力衰竭患者的预后。然而，这种有益作用的确切机制尚不清楚。在本研究中，使用脑心肌炎病毒感染导致的急性病毒性心肌炎小鼠模型，维司力农治疗可显著提高生存率并减轻心肌损伤。相比之下，磷酸二酯酶抑制剂氨力农治疗并未提高生存率。虽然维司力农没有抑制病毒复制或保护心肌细胞免受病毒直接细胞损伤，但它确实抑制了病毒感染后自然杀伤细胞活性的增加。另一方面，氨力农未能抑制自然杀伤细胞活性。维司力农和氨力农均抑制了肿瘤坏死因子-α的产生。因此，我们推测维司力农通过抑制自然杀伤细胞活性发挥其有益作用，并且它作为一种免疫调节剂为病毒性心肌炎和/或免疫性疾病的治疗提供了新的治疗可能性。
