ATTENUATION OF MYOCARDIAL STUNNING BY THE ACE-INHIBITOR RAMIPRILAT THROUGH A SIGNAL CASCADE OF BRADYKININ AND PROSTAGLANDINS BUT NOT NITRIC-OXIDE
ATTENUATION OF MYOCARDIAL STUNNING BY THE ACE-INHIBITOR RAMIPRILAT THROUGH A SIGNAL CASCADE OF BRADYKININ AND PROSTAGLANDINS BUT NOT NITRIC-OXIDE
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DOI：
10.1161/01.cir.90.3.1368
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发表时间：
1994-09-01
期刊：
影响因子：
37.8
通讯作者：
HEUSCH, G
中科院分区：
文献类型：
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作者：
EHRING, T;BAUMGART, D;HEUSCH, G
背景：已证实几种血管紧张素转换酶(ACE)抑制剂可减轻心肌顿抑。方法和结果在第一个方案中，我们研究了缓激肽的作用，并分析了不加和加用缓激肽B-2受体拮抗剂的ACE抑制剂雷米普利拉对局部心肌血流量(有色微球)和功能(声学显微镜)的影响。32只安氟醚/N2O麻醉开胸犬结扎冠状动脉左回旋支(LCx)15min，再灌流4h。8只犬作为安慰剂对照组(组1)，8只犬在结扎Lcx前静脉注射雷米普利拉(20µg/kg)(组2)。8只犬在缺血再灌流期间冠状动脉内持续输注HOE 140[0.5 ng/(mL.min)ic](第3组)，8只犬在缺血再灌流期间从给予雷米普利拉前45min开始连续输注HOE 140(第4组)。平均主动脉压通过主动脉内球囊保持恒定，心率在整个实验方案中没有变化。在对照组和心肌缺血时，四组犬后壁跨壁血流量(BF)和收缩期壁增厚(WT)无明显差异。再灌流4h时，组1(-10+/-20%)、组3(-18+/-12%)、组4(-12+/-21%)WT仍低于对照组，而组2 WT已恢复至对照组的55+/-20%(P
Background Attenuation of myocardial stunning by several angiotensin-converting enzyme (ACE) inhibitors has been demonstrated. However, the signal cascade mediating such protective effect has not been analyzed in detail so far.Methods and Results In a first protocol, we addressed the role of bradykinin and analyzed the effect of the ACE inhibitor ramiprilat without and with added bradykinin B-2 receptor antagonist HOE 140 on regional myocardial blood flow (colored microspheres) and function (sonomicrometry). Thirty-two enflurane/N2O-anesthetized open-chest dogs were subjected to 15 minutes of occlusion of the left circumflex coronary artery (LCx) and 4 hours of subsequent reperfusion. Eight dogs served as placebo controls (group 1), and 8 dogs received ramiprilat (20 mu g/kg IV) before LCx occlusion (group 2). Eight dogs received a continuous intracoronary infusion of HOE 140 [0.5 ng/(mL.min) IC] during ischemia and reperfusion (group 3), and in 8 dogs HOE 140 was infused continuously during ischemia and reperfusion, starting 45 minutes before the administration of ramiprilat (group 4). Mean aortic pressure was kept constant with an intra-aortic balloon, and heart rate did not change throughout the experimental protocols. Under control conditions and during myocardial ischemia, posterior transmural blood flow (BF) and systolic wall thickening (WT) were not different in the four groups of dogs. However, at 4 hours of reperfusion, WT was still depressed in groups 1 (-10+/-20% of control [mean+/-SD]), 3 (-18+/-12% of control), and 4 (-12+/-21% of control), whereas WT in group 2 had recovered to 55+/-20% of control (P