Role of endothelin in a rabbit model of acute myocardial infarction: effects of receptor antagonists.
Role of endothelin in a rabbit model of acute myocardial infarction: effects of receptor antagonists.
复制标题
内皮素在兔急性心肌梗死模型中的作用：受体拮抗剂的作用。
DOI：
10.1097/00005344-199612000-00007
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发表时间：
1996
影响因子：
3
通讯作者：
Murray,JJ
中科院分区：
文献类型：
--
作者：
Vitola,JV;Forman,MB;Holsinger,JP;Kawana,M;Atkinson,JB;Quertermous,T;Jackson,EK;Murray,JJ
用家兔急性心肌梗塞模型，观察内皮素（ET）在急性心肌梗塞及保护心肌中的作用。一组结扎兔回旋支30 min，再灌注3 h，测定心肌血流量和心肌ET-1 mRNA水平。在第二组中，在用盐水、FR 139317（一种ET A受体拮抗剂）或PD 145065（一种ET A和ET B受体拮抗剂）预处理的动物中研究外源性ET的全身和冠状动脉效应。在第三项研究中，用外源性ET-1、FR 139317、PD 145065或生理盐水处理经历30分钟回旋支闭塞随后48小时再灌注的动物。在48 h时记录心律失常并测量梗死面积。这些研究表明，兔缺血和再灌注后会出现进行性微循环衰竭（“无复流现象”）。与非缺血区相比，缺血区心肌ET-1 mRNA水平升高2.6倍（p= 0.04）。外源性ET-1引起冠状动脉和全身血管阻力的升高，这种升高可被ET A受体的拮抗作用显著阻断。在兔心肌缺血和再灌注，ET-1输注导致室性心律失常的发生率较高，而ET受体拮抗剂PD 145065显着减少室性心律失常。与对照组相比，外源性ET-1和FR 139317不能改变危险区（AR）的梗死面积（AN）[AN/AR（%）分别为46±8、55±9和47±7]。然而，PD 145065显著降低AN/AR（22±7; p≤ 0.02）。再灌注后ET-1 mRNA水平的增加可能导致无复流现象的发生。虽然ET-1的血管收缩作用可被单独的ET A受体拮抗剂阻断，但只有阻断ET A和ET B受体才能显著减少梗死面积。这些数据表明，生产ET增加在心脏缺血期间，是有害的再灌注心肌。
The role of endothelin (ET) in acute myocardial infarction and proarrhythmic potential was investigated in a rabbit model. One group of rabbits underwent 30 min of circumflex occlusion and 3 h of reperfusion with measurements of myocardial blood flow and myocardial levels of ET-1 messenger RNA (mRNA). In a second group, the systemic and coronary effects of exogenous ET were studied in animals pretreated with either saline, FR139317, an ET A-receptor antagonist, or PD145065, an ET A-and ET B-receptor antagonist. In a third study, animals undergoing 30 min of circumflex occlusion followed by 48 h of reperfusion were treated with exogenous ET-1, FR139317, PD145065, or saline. Arrhythmias were recorded and infarct size measured at 48 h. These studies revealed that ischemia and reperfusion was followed by a progressive microcirculatory failure (“no-reflow phenomenon”) in rabbits. This was associated with a 2.6-fold elevation in levels of myocardial ET-1 mRNA in the ischemic zone in comparison to the nonischemic zone (p= 0.04). Exogenous ET-1 caused elevation in coronary and systemic vascular resistance that was significantly blocked by antagonism of the ET A receptor. In rabbits subjected to myocardial ischemia and reperfusion, ET-1 infusion led to a higher incidence of ventricular arrhythmias, whereas ET-receptor antagonism with PD145065 significantly reduced ventricular arrhythmias. Exogenous ET-1 and FR139317 failed to alter infarct size (AN) of the area at risk (AR) compared with control [AN/AR (%) was 46±8, 55±9, and 47±7, respectively]. However, PD145065 significantly decreased AN/AR (22±7; p≤ 0.02). The increased production of ET-1, resulting from increased levels of mRNA after reperfusion, may contribute to the no-reflow phenomenon. Although the vasoconstrictor effects of ET-1 can be blocked by ET A-receptor antagonism alone, only blockade of both the ET A and ET B receptors significantly reduced infarct size. These data suggest that production ET increases in the heart during ischemia and is deleterious to the reperfused myocardium.