A serine elastase inhibitor reduces inflammation and fibrosis and preserves cardiac function after experimentally-induced murine myocarditis

In viral myocarditis, inflammation and destruction of cardiac: myocytes lea ds to fibrosis, causing progressive impairment in cardiac function. Here we show the etiologic importance of serine elastase activity in the pathophys iology of acute viral myocarditis and the therapeutic efficacy of an elasta se inhibitor. In DBA/2 mice inoculated with the encephalomyocarditis virus, a more than 150% increase in myocardial serine elastase activity is observ ed. This is suppressed by a selective serine elastase inhibitor, ZD0892, wh ich is biologically effective after oral administration. Mice treated with this compound had little evidence of microvascular constriction and obstruc tion associated with myocarditis-induced ischemia reperfusion injury, much less inflammation and necrosis, only mild fibrosis and myocardial collagen deposition, and normal ventricular function, compared with the infected non treated group.