Stark G, Windisch M, Haller E M, Stark U, Pieber T, Pilger E, Krejs G J, Tritthart H A
Karl-Franzens University, Graz, Austria.
Cardiovasc Res. 1991 Oct;25(10):807-14. doi: 10.1093/cvr/25.10.807.
The aim was to evaluate the effects of tissue concentration of amiodarone on ultrastructure and electrical activity in isolated spontaneously beating Langendorff perfused guinea pig hearts.
Group 1: The influence of 10 microM amiodarone over a period of 1 h in a non-recirculated perfusate on conduction intervals, heart rate, creatine kinase concentration in the coronary effluent, coronary flow, and drug accumulation was determined. Group 2: Ultrastructural changes after 30 min and 60 min perfusion with amiodarone were examined. Group 3: Cardiac refractoriness was evaluated following 30 min and 60 min of perfusion with amiodarone. EXPERIMENTAL PREPARATIONS: Isolated hearts of guinea pigs (200-300 g) were used: group 1, n = 6 animals; group 2, n = 3 for each time span; and group 3, n = 6 for each time span.
A steady state for the effects of amiodarone on atrioventricular and intraventricular conduction [+31(SEM 5)%, p less than 0.01% +47(12)%, p less than 0.01, respectively] and on heart rate [-30(9)%, p less than 0.01] was reached after 15 min, and on His bundle conduction [+38(17)%, p less than 0.01] after 30 min. QT duration was not affected throughout the duration of the experiment. Cardiac refractoriness was significantly prolonged following 30 min perfusion with 10 microM amiodarone, and was further significantly increased following 60 min perfusion. Amiodarone tissue concentration increased to 365(39) nmol.g-1 wet weight, and this was accompanied by an increase in creatine kinase concentration in the coronary effluent. Coronary flow stayed constant throughout the whole experiment. At the end of the experiment electron microscopic examination of the myocardium of the left ventricle showed accumulation, fusion, and vacuolisation of mitochondria, and perinuclear oedema.
These observations suggest that amiodarone, as well as exerting acute electrophysiological effects, creates ultrastructural changes which probably contribute to its effectiveness in arrhythmias caused by scarred myocardium.
本研究旨在评估胺碘酮组织浓度对离体自发搏动的Langendorff灌注豚鼠心脏超微结构和电活动的影响。
第1组：测定10微摩尔胺碘酮在非循环灌注液中作用1小时对传导间期、心率、冠脉流出液中肌酸激酶浓度、冠脉流量及药物蓄积的影响。第2组：检查胺碘酮灌注30分钟和60分钟后的超微结构变化。第3组：评估胺碘酮灌注30分钟和60分钟后的心脏不应期。实验准备：使用豚鼠（200 - 300克）的离体心脏：第1组，n = 6只动物；第2组，每个时间点n = 3只；第3组，每个时间点n = 6只。
胺碘酮对房室和室内传导[分别增加31（标准误5）%，p < 0.01；增加47（12）%，p < 0.01]以及心率[降低30（9）%，p < 0.01]的作用在15分钟后达到稳态，对希氏束传导[增加38（17）%，p < 0.01]的作用在30分钟后达到稳态。在整个实验过程中QT间期未受影响。用10微摩尔胺碘酮灌注30分钟后心脏不应期显著延长，灌注60分钟后进一步显著增加。胺碘酮组织浓度增加至365（39）纳摩尔·克-1湿重，同时冠脉流出液中肌酸激酶浓度增加。在整个实验过程中冠脉流量保持恒定。实验结束时，左心室心肌的电子显微镜检查显示线粒体堆积、融合和空泡化以及核周水肿。
这些观察结果表明，胺碘酮除了发挥急性电生理作用外，还会引起超微结构变化，这可能有助于其对瘢痕心肌所致心律失常的疗效。
