Horkay F, Gellér L, Kiss O, Szabó T, Vagó H, Kékesi V, Juhász-Nagy A, Merkely B
Department of Cardiovascular Surgery, Semmelweis Medical University, Budapest, Hungary.
J Cardiovasc Pharmacol. 2000 Nov;36(5 Suppl 1):S320-2. doi: 10.1097/00005344-200036051-00093.
In earlier studies severe ventricular arrhythmias developed during intrapericardial (i.p.) endothelin-1 (ET-1) infusion. Monophasic action potential duration (MAPD90) increase and significant ST segment elevation preceded the onset of arrhythmias. The aim of this study was to test the antiarrhythmic and anti-ischemic efficacy of the mixed endothelin-A- and -B- (ETA/B) receptor antagonist bosentan (BOS) on ET-1-induced arrhythmias on six mongrel dogs. Ten minutes after an intravenous bolus dose of BOS (10 mg/kg), ET-1 (33 pmol/kg/min) was given into the pericardial space for 30min (BOS group). Six control dogs received only ET-1 infusion (control group). Mean arterial blood pressure (MAP), cardiac output, electrocardiograph (ECG), right and left ventricular endo- and epicardial (RVEND, RVEP, LVEND, LVEP) MAPD90s were recorded. MAP and cardiac output did not change significantly in the BOS group. Significant MAPD90 prolongation was found in all investigated regions of the control group (ET start vs ET 20 min: LVEP, 174 +/- 3 vs 208 +/- 10*; RVEND, 206 +/- 9 vs 241 +/- 12* ms, *p < 0.05), while significant MAPD90 alterations were not observed in the BOS group (basic vs ET 20 min: RVEP, 189 +/- 5 vs 196 +/- 5; LVEP, 199 +/- 5 vs 199 +/- 4; RVEND, 194 +/- 5 vs 195 +/- 6; LVEND, 209 +/- 3 vs 213 +/- 5 ms). Early after depolarizations (EADs) were observed in three control dogs. Severe ventricular arrhythmias [incessant nonsustained ventricular tachycardias (nsVTs) in all cases, sustained VTs (sVTs) in four, ventricular fibrillation (VF) in two instances] were present in the control group, whereas nsVTs were observed only in two dogs in the BOS group. ST segment elevation was more pronounced in the control group than in the BOS group (1.01 +/- 0.2 vs 0.41 +/- 0.07 mV, p < 0.05). In summary, bosentan effectively inhibits intrapericardial ET- 1-induced ventricular arrhythmias, moreover it may have a protective effect against epimyocardial ischemia.
在早期研究中，在心包内（i.p.）输注内皮素-1（ET-1）期间出现了严重的室性心律失常。在心律失常发作之前，单相动作电位时程（MAPD90）增加且ST段显著抬高。本研究的目的是测试内皮素A和B（ETA/B）受体混合拮抗剂波生坦（BOS）对6只杂种犬ET-1诱导的心律失常的抗心律失常和抗缺血疗效。静脉推注BOS（10mg/kg）10分钟后，将ET-1（33pmol/kg/min）注入心包腔30分钟（BOS组）。6只对照犬仅接受ET-1输注（对照组）。记录平均动脉血压（MAP）、心输出量、心电图（ECG）、右心室和左心室心内膜和心外膜（RVEND、RVEP、LVEND、LVEP）的MAPD90。BOS组的MAP和心输出量无显著变化。对照组所有研究区域均出现显著的MAPD90延长（ET开始时与ET 20分钟时：LVEP，174±3 vs 208±10*；RVEND，206±9 vs 241±12* ms，*p<0.05），而BOS组未观察到显著的MAPD90改变（基础值与ET 20分钟时：RVEP，189±5 vs 196±5；LVEP，199±5 vs 199±4；RVEND，194±5 vs 195±6；LVEND，209±3 vs 213±5 ms）。在3只对照犬中观察到早期后除极（EADs）。对照组出现严重的室性心律失常[所有病例均为持续性非持续性室性心动过速（nsVTs），4例为持续性室性心动过速（sVTs），2例为心室颤动（VF）]，而BOS组仅在2只犬中观察到nsVTs。对照组的ST段抬高比BOS组更明显（1.01±0.2 vs 0.41±0.07 mV，p<0.05）。总之，波生坦有效抑制心包内ET-1诱导的室性心律失常，并可能对心外膜缺血具有保护作用。
