726-1 Expression of Inducible Nitric Oxide Synthase in the Myocardium of Acute Myocarditis – A Serial Cardiac Biopsy Study

In endotoxin shock, hypotension and impaired myocardial contractility may be caused by increased nitric oxide (NO) formed by inducible NO synthase (iNOS) which is induced by cytokines and bacterial lipopolysaccarides.We have investigated whether iNOS is expressed in serially biopsied samples from the right ventricle of 20 cases of acute myocarditis by immunohistochemistry and in situ hybridization. Distinct iNOS immunoreactivity was observed in cardiomyocytes, endothelial cells, vascular smooth muscle cells and macrephages in all cases during acute active stage, in which cardiac function was severely impaired. Immunoelectron microscopic distribution of iNOS was evident in the cytosol of these cells. However, little staining was disclosed in the myocardium during the convalescent stage, showing normal cardiac function. The distribution of myocytes with elevated iNOS mRNA concentration was identical to that of these immunoreactive cells.ConclusionsThe present study shows the expression of human myocardial iNOS in acute myocarditis, suggesting that the enhanced production of NO by iNOS is cytotoxic and accounts, in part, for myocardial injury and reduced myocardial contractility during acute illness