Inhibition of the Na+/H+ exchanger confers greater cardioprotection against 90 minutes of myocardial ischemia than ischemic preconditioning in dogs

Inhibition of the Na+/H+ exchanger confers greater cardioprotection against 90 minutes of myocardial ischemia than ischemic preconditioning in dogs
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DOI:
10.1161/01.cir.100.25.2519
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发表时间:
1999-12-21
期刊:
影响因子:
37.8
通讯作者:
Gross, GJ
Gross, GJ
中科院分区:
医学1区
文献类型:
--
作者:
Gumina, RJ;Buerger, E;Gross, GJ

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背景-本研究比较了缺血预处理(IPC)和钠-氢交换器(NHE)-1抑制对减少由90分钟缺血损伤诱导的梗死面积(IS)的功效,并检测了NHE-1抑制和IPC之间的相互作用。方法和结果-在犬梗死模型中,通过1或4次5分钟冠状动脉闭塞产生的IPC,或特异性NHE-1抑制剂BIIB 513,0.75或3.0 mg/kg,在60或90分钟冠状动脉闭塞前15分钟给药,随后再灌注3小时。通过TTC染色测定IS,并表示为风险面积(IS/AAR)的百分比。尽管IPC和0.75 mg/kg BIIB 513在60分钟闭塞模型中均产生了相当且显著的IS/AAR降低,但在90分钟闭塞模型中观察到IS/AAR的降低不显著。然而,3.0 mg/kg BIIB 513在两种模型中均显著降低IS(P
Background-This study compared the efficacy of ischemic preconditioning (IPC) and sodium-hydrogen exchanger (NHE)-1 inhibition to reduce infarct size (IS) induced by a 90-minute ischemic insult and examined the interaction between NHE-1 inhibition and IPC,Methods and Results-In a canine infarct model, either IPC, produced by I or four 5-minute coronary artery occlusions, or the specific NHE-1 inhibitor BIIB 513, 0.75 or 3.0 mg/kg, was administered 15 minutes before either a 60- or 90-minute coronary artery occlusion followed by 3 hours of reperfusion. IS was determined by TTC staining and expressed as a percentage of the area at risk (IS/AAR), Although both IPC and BIIB 513 at 0.75 mg/kg produced comparable and significant reductions in IS/AAR in the 60-minute occlusion model, insignificant reductions in IS/AAR were observed in the 90-minute occlusion model. However, BIIB 513 at 3.0 mg/kg markedly reduced IS in both models (P