| Mechanisms of the pathogenesis of myocardial stunning are not fully understood. It has been known that reactive oxygen species(ROS) production increases in myocardial stunning and ROS depress myocardial function. But it is unclear whether ROS impair myocardium directly or through the formation of other substances. Recently, it has been demonstrated that ischemialreperfusion(I/R) leads to the activation of nitric oxide synthase (NOS) and nitric oxide(NO) participates in the regulation of hemodynamic and microcirculatory changes in organic hR. The dual role of NO as a cytoprotective or a cytotoxic free radical gas has been noted in various types of pathophysiological conditions. However, It is controversial whether NO is protective or deleterious against myocardial hR injury? Recent studies suggest that peroxynitrite(ONOO ) formed by the reaction of NO with superoxide plays an important role in the cell damages caused by superoxide. Additionally, there is a continuing debate as to the effects of inhibitors of NOS on myocardial hR injury. Finally, whether intramyocardial microcirculatory dysfunction occurs in stunned myoeardiurn is an unresolved issue. The purposes of this study were (1) to research the intramyocardial microcirculatory derangement and its mechanism during myocardial stunning, (2) to study the roles of NO and ONOO in the pathogenesis of myocardial stunning and their mechanisms, (3) to evaluate the effects of a nonselective NOS inhibitor, N -nitro-L-arginine methyl ester(NAME), a selective inducible NOS(iNOS) inhibitor, aminoguanidine (AMD), and an antioxidant, polysaccharide krestin(PSK), on microcireulatory changes, myocardial performance and structural damages after myocardial stunning. Methods Thirty-nine adult mongrel dogs of male, weighing 13-18 kg, anesthetized with sodium pentobarbital, were randomly assigned to six groups. (I )Myocardial stunning after a short-time ischemia(MSS) group: dogs underwent 15 mm of left anterior descending coronary artery(LAD) occlusion, followed by 120 mm reperfusion. (2)Myocardial stunning after a long-time ischemia(MSL) group: dogs underwent 60 mm of LAD occlusion, followed by 120 mm reperfusion. (3)NAME group: dogs underwent the same hR as MSL group, received NAME(lOmg/kg). One-third of NAME dose was given intravenously 10 mm prior to LAD occlusion, and the rest was infused continuously intravenously from 10 mm before reperfusion to the end of reperfusion. (4)AMD group: dogs were subjected to the same I/R as MSL group, received AMD(l0Omg/kg). AMD was given by the same way as NAME. (5)PSK group: animals were subjected to the same J/R, received PSK. which was administered orally, at a dose of 150mg/kg once daily for two day抯 before thoracotomy. (6)Sham operation(SHAO) group. Myocardial contrast echocardiography (MCE) was performed using intravenous perfluoropropane-exposed sonicated dextrose albumin(0.Olml/kg) at baseline, during coronary occlusion, and at 5,30,60.90.and 120 mm after reperfusion. At baseline. 5.60,and 120 mm after reperfusion. acetylcholine (ACH, 10 1-? g/kg) and nitroglycerin(NG. 10 p g/kg) were given from aortic root injections after resting MCE, respectively, and MCE was repeated immediately, respectively. Electrocardiogram-gated end-systolic images in short axis were acquired in harmonic mode and digitized on-line. Left ventricular function was evaluated by?echocardiography using an echocardiogram at the above time points. Hemodynamics was measured by...
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