STUDY ON THE ROLE OF Na_+-H_+ EXCHANGE ON ISCHEMIA-REPERFUSION INjURY

Na_-H_交换对缺血再灌注损伤作用的研究

• 批准号: 07670816
• 负责人: WAKIDA Yasushi
• 金额: $ 1.47万
• 依托单位: AICHI MEDICAL UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07670816/
• 关键词: Reperfusion injury; Na^+-H^+ exchange; SSwine in vivo model; 再潅流障害; Na^+-H^+変換系; アミロライド; 収縮帯壊死; 単相活動電位; 再灌流不整脈

The inhibition of Na<@D1+@>D1-H<@D1+@>D1 exchange (NHE) with amiloride analogues in vitro has been shown to prevent reperfusion arrythmias and additional cell necrosis. Inhibition of intracellular Ca<@D12+@>D1 overload via NHE inhibition has been suggested as a mechanism of these protective effects. The aim of this study was to examine whether treatment with amiloride analogues reduces the incidence of reperfusion arrythmias and limits infarct size in vivo. Open-chest swine were exposed to a 30 min left anterior descending artery occlusion and 180 min reperfusion during atrial pacing at 150 ppm. In protocol 1, intravenous 5-(N,N-dimethyl)-amiloride (AML) 5mug/kg/min was administered 10 min before coronary occlusion in the treatment group (n=7) and intravenous saline in the control group (n=7). In protocol 2, an intravenous bolus injection of AML 1mg/kg was performed 5 min before reperfusion and followed by 5mug/kg/min intravenous injection in the treatment group (n=7) and saline in the … More control group (n=8). There was no significant difference in the size of the area at risk and hemodynamic parameters between the treatment ans control groups both in the protocols. However, the infarcted area was 0.4(]SY.+-。[)1.0% of the area at risk in the treatment group of the protocol 1, whereas it was 62(]SY.+-。[)29% in the control group (p<0.05). The infarcted area in the treatment group of the protocol 2 was also significantly smaller than that in the control group (10.3(]SY.+-。[)7.1% vs.42.3(]SY.+-。[)18.8%, p<0.05). Pathological examination revealed that all of the infarcted area consisted of contraction band necrosis. There was no significant difference in the incidence of ventricular arrhythmias after reperfusion between the groups in the protocols. Inhibition of NHE with AML prevented reperfusion related cell necrosis in the in vivo swine model. This effect was augmented if the drug was administered before ischemia. However, even if the drug was administered after ischemia (before reperfusion), there was significant reduction of the infarcted area. In this experimental model, there was no effect on reperfusion arrhythmia in the both protocols. Less

体外用阿米洛利类似物抑制Na&lt；@d1+@&gt；d1-H&lt；@d1+&gt；d1交换(NHE)已被证明能防止再灌注性心律失常和额外的细胞坏死。通过抑制NHE抑制细胞内钙超载可能是这些保护作用的机制之一。这项研究的目的是检验阿米洛利类似物的治疗是否能降低再灌注性心律失常的发生率，并限制体内的梗塞范围。开胸猪在150ppm的心房起搏时，结扎左前降支30min，再灌流180min。方案1：治疗组术前10min静脉注射5-(N，N-二甲基)-阿米洛利(AML)5 mg/kg/min，对照组(n=7)静脉注射生理盐水。在方案2中，治疗组(n=7)在再灌注前5分钟静脉注射AML1 mg/kg，然后静脉注射5 mg/kg/min，并在…中注射生理盐水多设对照组(n=8)。在两个方案中，治疗组和对照组之间的危险区域大小和血流动力学参数没有显著差异。而梗塞面积为0.4(Sy.+-)。[]在方案1的治疗组中，危险区域的1.0%，而方案1的治疗组为62()sy.+-。对照组29%(P&lt；0.05)。方案2治疗组的脑梗塞面积也明显小于对照组(10.3士+-)。[)7.1%与42.3()SY+-。[)18.8%，p&lt；0.05)。病理检查显示梗死区全部由收缩带坏死组成。两组再灌注后室性心律失常的发生率差异无统计学意义。AML抑制NHE可预防活体猪模型中再灌注相关的细胞坏死。如果在缺血前给药，这种作用就会增强。然而，即使在缺血后(再灌流前)给药，梗死面积也显著减少。在本实验模型中，两种方案对再灌注性心律失常均无影响。较少

项目成果

Uesugi M., Wakida Y., Fukuta M., Watabe K., Iwa T., Kobayashi T.: "of Na^+-H^+ Exchange Inhibitor Administrated Before Reperfusion Reduces Myocardial Necrosis in Open Chest Swine Model" XIXth Congress of the European Society of Cardiology. Stockholm Swede

Uesugi M.、Wakida Y.、Fukuta M.、Watabe K.、Iwa T.、Kobayashi T.：“再灌注前施用 Na^ -H^ 交换抑制剂可减少开胸猪模型中的心肌坏死”第十九届欧洲大会

福田 元敬: "虚血再灌流障害におけるNa^+-H^+exchange inbibitor の関与について" 愛知医科大学医学会雑誌. 24. 579-587 (1996)

Mototaka Fukuda：“Na^+-H^+交换抑制剂参与缺血再灌注损伤”爱知医科大学医学会杂志 24. 579-587 (1996)。

Motokuki Fukuta: "Role of Na^+-H^+ Exchange Inhibitor on Ischemia-reperfusion Injury" J.Aichi.Med.Univ.Assoc. 24. 579-587 (1996)

Motokuki Fukuta：“Na^ -H^ 交换抑制剂对缺血再灌注损伤的作用”J.Aichi.Med.Univ.Assoc。

Motouki Fukuta, Yasushi Wakida, Toru Iwa, Michitaka Uesugi, Tadashi Kobayashi.: "Role of Na^+-H^+ Exchange on Reperfusion Related Myocardial Injury and Arrhythmias in an Open-Chest Swine Model" PACE. 19[Pt.II]. 2027-2033 (1996)

Motouki Fukuta、Yasushi Wakida、Toru Iwa、Michitaka Uesugi、Tadashi Kobayashi。：“开胸猪模型中 Na^ -H^ 交换对再灌注相关心肌损伤和心律失常的作用”PACE。

MOTOYUKI FUKUTA YASUSHI WAKIDA: "Role of Na^+-H^+ Exchange on Reperfusion Related Myoconclial Injury and Arrhythmias in an Open Chest Swine Model" PACE. 19. 2027-2033 (1996)

MOTOYUKI FUKUTA Yasushi WAKIDA：“开胸猪模型中 Na^ -H^ 交换对再灌注相关肌腱损伤和心律失常的作用”PACE。