Wainwright C L, Parratt J R
Department of Physiology and Pharmacology, University of Strathclyde, Glasgow, Scotland.
Cardiovasc Res. 1991 Feb;25(2):93-100. doi: 10.1093/cvr/25.2.93.
It has been suggested that the balance between the release from the heart of prostacyclin and thromboxane A2 is a major determinant of the severity of arrhythmias during ischaemia and reperfusion. This has been examined in a dog model.
Three different cyclo-oxygenase inhibitors in doses adequate to prevent formation of both prostacyclin and thromboxane--aspirin (7 mg.kg-1), flurbiprofen (3 mg.kg-1), and sodium meclofenamate (2 mg.kg-1) with or without nafazatrom or dazmegrel--were given prior to a combined occlusion-reperfusion insult, and the severity of resulting arrhythmias examined.
Adult greyhound dogs were used: controls n = 29; aspirin n = 10; flurbiprofen n = 10; sodium meclofenamate +/- nafazatrom or dazmegrel n = 22.
None of the interventions modified the severity of ischaemic arrhythmias induced by coronary artery occlusion and release. The numbers of ventricular extrasystoles during the 40 min occlusion period were similar in all groups: controls 653(SEM 109); aspirin 690(187); flurbiprofen 454(132); meclofenamate 833(218). Ventricular fibrillation from the combined occlusion-reperfusion insult was also similar; controls 83%; aspirin 80%; flurbiprofen 80%; meclofenamate 100%. In the doses used all three inhibitors prevented the increase in plasma concentrations of thromboxane A2 [from 104(23) to 166(34) pg.ml-1] and prostacyclin [from 450(80) to 720(110) pg.ml-1] seen in control untreated dogs subjected to coronary artery occlusion. The addition of sodium meclofenamate to either nafazatrom (10 mg.kg-1 orally) or dazmegrel (3 mg.kg-1 intravenously), which when given alone are markedly protective, abolished this protection.
The results show the importance of maintaining prostacyclin release in modifying the severity of ischaemic and reperfusion arrhythmias, and again suggest that prostacyclin is an "endogenous antiarrhythmic substance".
有人提出，心脏释放前列环素和血栓素A2之间的平衡是缺血和再灌注期间心律失常严重程度的主要决定因素。这一点已在犬模型中得到研究。
在进行联合闭塞-再灌注损伤之前，给予三种不同剂量的环氧化酶抑制剂，这些剂量足以防止前列环素和血栓素的形成——阿司匹林（7毫克/千克）、氟比洛芬（3毫克/千克）和甲氯芬那酸钠（2毫克/千克），同时使用或不使用萘呋胺酯或达唑麦角——并检查由此产生的心律失常的严重程度。
使用成年灵缇犬：对照组n = 29；阿司匹林组n = 10；氟比洛芬组n = 10；甲氯芬那酸钠±萘呋胺酯或达唑麦角组n = 22。
没有一种干预措施改变冠状动脉闭塞和再灌注所诱发的缺血性心律失常的严重程度。在40分钟的闭塞期内，所有组的室性早搏数量相似：对照组653（标准误109）；阿司匹林组690（187）；氟比洛芬组454（132）；甲氯芬那酸钠组833（218）。联合闭塞-再灌注损伤导致的心室颤动也相似；对照组83%；阿司匹林组80%；氟比洛芬组80%；甲氯芬那酸钠组100%。在所使用的剂量下，所有三种抑制剂都能防止血浆中血栓素A2浓度[从104（23）升至166（34）皮克/毫升]和前列环素浓度[从450（80）升至720（110）皮克/毫升]的升高，而在未治疗的冠状动脉闭塞对照犬中可观察到这种升高。将甲氯芬那酸钠与单独使用时具有显著保护作用的萘呋胺酯（口服10毫克/千克）或达唑麦角（静脉注射3毫克/千克）联合使用，会消除这种保护作用。
结果表明，维持前列环素的释放对于改变缺血和再灌注心律失常的严重程度很重要，并再次表明前列环素是一种“内源性抗心律失常物质”。
