Role of Oxidative Stress in the Pathogenesis of Myocardial Stunning in Dogs and Effects of Aminoguanidine / 中华高血压杂志

ABSTRACT

Back ground Superoxide anion produced by oxidative stress combined with nitric oxide(NO)released by cellular NO synthase(NOS)generates peroxynitrite(ONOO-)which was one of reactive oxygen species.Objective To study the role of peroxynitrite in the pathogenesis of myocardial stunning(MS)and the effects of aminoguanidine(AMD).Methods Twenty-four dogs were randomly divided into four groups(1)Short-time myocardical stunning(MS)groupthe animals underwent 15 min occlusion of left anterior descending coronary artery(LAD),followed by 120 min of reperfusion.(2)Long-time MS group60 min of LAD occlusion,followed by 120 min of reperfusion.(3)AMD groupDogs were subjected to the same ischemia/reperfusion management as Long-MS group,but AMD was administrated(total 100 mg/kg).(4)Sham-operation group.Left ventricular function was evaluated by echocardiography and blood samples were taken from coronary venous sinus for the examination of NO at different time points.The stunned myocardium was examined immunohistochemically and electronic microscope.Results(1)Systolic thickening of stunned myocardium region and left ventricular ejection fraction were markedly declined during LAD occlusion in the 3 experimental groups,but progressively improved with the time of reperfusion.The improvement was faster in short-MS and AMD groups than in long-MS group.(2)Plasma NO concentrations in coronary venous sinus were greatly increased during reperfusion in short-and long-MS group,while no significant elevation was found in AMD group.(3)A marked increase in the immunoreactivity to nitrotyrosine,a specific "footprint" of peroxynitrite,was shown in the stunned myocardium both in short-and long-MS group,with larger and stronger positive foci in long-MS group.The positive staining was located in myocardial cytoplasm,especially at myofibrils and contractile bands.Treatment with AMD significantly reduced the nitrotyrosine staining in the stunned myocardium.(4)No ultrastructural changes of myocardial cells were noted in stunned myocardium in short-MS group except a slight loss of mitochondrial granules.On the contrary,myocyte edema,myofilament fractures,granule loss and swelling of mitochondrias were significant in long-MS group.AMD significantly ameliorated the ultrastructural abnormalities.Conclusion Myocardial stunning was associated peroxynitrite with production which mainly deteriorate the contractile proteins of myofibrils.AMD significantly inhibit the peroxynitrite formation leading to attenuation of the ultrastructural and functional injuries of stunned myocardium.