BACKGROUND: Despite intense investigation, the effector of the infarct-limiting protection observed during the late phase of ischemic preconditioning (PC) remains unknown. The goal of this study was to test the hypothesis that late PC against myocardial infarction is mediated by the activity of nitric oxide synthase (NOS). METHODS AND RESULTS: Conscious rabbits underwent a 30-minute coronary occlusion followed by 3 days of reperfusion. In group I (control group, n= 10), infarct size (tetrazolium staining) averaged 56.8+/-5.3% of the risk region, which was decreased to 27.6+/-2.5% (P<0.05) in rabbits preconditioned 24 hours earlier with a sequence of six 4-minute occlusion/4-minute reperfusion cycles (group II, n= 10). When preconditioned rabbits were given the nonselective NOS inhibitor N(omega)-nitro-L-arginine (L-NA, 13 mg/kg i.v. [group III, n=8]) or the selective iNOS inhibitor aminoguanidine (AG, 150 mg/kg SC [group V, n=7]) before the 30-minute occlusion, the protective effect of late PC was completely abrogated; that is, infarct size (59.9+/-4.5% and 65.8+/-3.3%, respectively) was similar to that measured in the control group. Measurements of systolic wall thickening (sonomicrometry) demonstrated that L-NA and AG also abolished the improved recovery of myocardial function effected by late PC in group II. When rabbits were given L-NA or AG without prior PC (group IV [n=8] and group VI [n=6], respectively), infarct size did not differ from that observed in controls (53.8+/-4.3% and 59.8+/-4.3%, respectively), demonstrating that L-NA and AG do not increase the extent of cell death in nonpreconditioned myocardium. CONCLUSIONS: Taken together, these results indicate that in the conscious rabbit, the infarct-sparing effect of the late phase of ischemic PC is mediated by the activity of NOS and suggest that the specific isoform primarily responsible for this cardioprotective phenomenon is iNOS. Thus, NO appears to be a pivotal component of the pathophysiological cascade of late PC.
BACKGROUND: Despite intense investigation, the effector of the infarct-limiting protection observed during the late phase of ischemic preconditioning (PC) remains unknown. The goal of this study was to test the hypothesis that late PC against myocardial infarction is mediated by the activity of nitric oxide synthase (NOS). METHODS AND RESULTS: Conscious rabbits underwent a 30-minute coronary occlusion followed by 3 days of reperfusion. In group I (control group, n= 10), infarct size (tetrazolium staining) averaged 56.8+/-5.3% of the risk region, which was decreased to 27.6+/-2.5% (P<0.05) in rabbits preconditioned 24 hours earlier with a sequence of six 4-minute occlusion/4-minute reperfusion cycles (group II, n= 10). When preconditioned rabbits were given the nonselective NOS inhibitor N(omega)-nitro-L-arginine (L-NA, 13 mg/kg i.v. [group III, n=8]) or the selective iNOS inhibitor aminoguanidine (AG, 150 mg/kg SC [group V, n=7]) before the 30-minute occlusion, the protective effect of late PC was completely abrogated; that is, infarct size (59.9+/-4.5% and 65.8+/-3.3%, respectively) was similar to that measured in the control group. Measurements of systolic wall thickening (sonomicrometry) demonstrated that L-NA and AG also abolished the improved recovery of myocardial function effected by late PC in group II. When rabbits were given L-NA or AG without prior PC (group IV [n=8] and group VI [n=6], respectively), infarct size did not differ from that observed in controls (53.8+/-4.3% and 59.8+/-4.3%, respectively), demonstrating that L-NA and AG do not increase the extent of cell death in nonpreconditioned myocardium. CONCLUSIONS: Taken together, these results indicate that in the conscious rabbit, the infarct-sparing effect of the late phase of ischemicPC is mediated by the activity of NOS and suggest that the specific isoform primarily responsible for this cardioprotective phenomenon is iNOS. Thus, NO appears to be a pivotal component of the pathophysiological cascade of late PC.
Authors: Gene T Yocum; John G Gaudet; Susie S Lee; Yaakov Stern; Lauren A Teverbaugh; Robert R Sciacca; Charles W Emala; Donald O Quest; Paul C McCormick; James F McKinsey; Nicholas J Morrissey; Robert A Solomon; E Sander Connolly; Eric J Heyer Journal: Stroke Date: 2009-03-12 Impact factor: 7.914
Authors: R Bolli; B Dawn; X L Tang; Y Qiu; P Ping; Y T Xuan; W K Jones; H Takano; Y Guo; J Zhang Journal: Basic Res Cardiol Date: 1998-10 Impact factor: 17.165