PARTICIPATION OF NITRIC-OXIDE AND PEROXYNITRITE IN THE DEVELOPMENT OFMYOCARDIAL TISSUE-DAMAGE IN ACUTE MYOCARDIAL-INFARCTION

Many factors, including superoxides, contribute to tissue damage in ac ute myocardial infarction (AMI). Excess nitric oxide (NO) produced by inducible NO synthase (iNOS) has also been reported to participate in myocardial injury associated with AMI, but its exact role remains uncl ear. To elucidate the role of NO and peroxynitrite in the pathogenesis of myocardial injury associated with AMI, we examined the expression of iNOS in the autopsied specimens of the left ventricle obtained from 15 patients with AMI and five with old MI by immunohistochemistry usi ng an anti-iNOS polyclonal antibody. The distribution of nitrotyrosine was also examined immunohistochemically. In patients who died from 12 hours to 3 weeks after the infarction, positive immunoreactivity for iNOS was observed in residual myocytes, macrophages, and vascular endo thelial cells in the peri-infarcted area. Degenerating myocytes in tha t area in all of that group showing positive staining for iNOS were al so stained positive for anti-nitrotyrosine antibody selfsame. These fi ndings were not observed in the myocardial specimens obtained from pat ients who died within 12 hours after the onset of AMI, showing a minim al number of inflammatory cells, or in the specimens from patients wit h an old myocardial infarction, which showed scar tissue and no cellul ar infiltration. Inducible NOS and nitrotyrosine were expressed in dam aged myocardium from patients with AMI, suggesting that the NO radical and peroxynitrite are involved in the pathogenesis of myocardial dama ge. (C) 1998 by Elsevier Science Inc.