Szekeres L, Németh M, Papp J G, Udvary E
Department of Pharmacology, Szent-Gvörgyi University Medical School, Szeged, Hungary.
Cardiovasc Res. 1990 Jan;24(1):37-41. doi: 10.1093/cvr/24.1.37.
STUDY OBJECTIVE - To determine whether the long lasting protection from early postocclusion and reperfusion arrhythmias induced by 7-oxo-prostacyclin is due to an anti-ischaemic effect alone or in combination with direct membrane effects. DESIGN - The study was performed on electrically stimulated isolated rabbit papillary muscle preparations with or without incubation with a stable prostacyclin analogue, 7-oxo-prostacyclinephedrine (7-oxo-PgI2). In some experiments, rabbits were pretreated with 7-oxo-PgI2. MEASUREMENTS and RESULTS - Marked prolongation of action potential duration (APD90) and effective refractory period developed 2 h after 20 min incubation with and subsequent washout of 7-oxo-PgI2, 1.1 X 10(-8) mol.litre-1. The same occurred if incubation with 7-oxo-PgI2 was maintained throughout the experiment. The only other change was a small diminution in amplitude of the action potential. During the 20 min incubation period neither APD90 nor effective refractory period was affected and only a transitory increase in the maximum rate of depolarisation, disappearing after washout, was seen. During the 4 h observation period there were no changes in the control preparations. The long lasting electrophysiological changes induced by 7-oxo-PgI2 were not affected by 60 min incubation with indomethacin, 2.8 X 10(-6) mol.litre-1. Pretreatment of rabbits with 7-oxo-PgI2, 50 micrograms.kg-1 intramuscularly, 48 h before the experiments prolonged effective refractory period v untreated controls. CONCLUSIONS - 7-oxo-PgI2 induces prolongation of APD90 and effective refractory period in adequately oxygenated normal papillary muscles as well as in ischaemic hearts. Therefore a direct membrane effect may contribute to its antiarrhythmic action, as well as an indirect anti-ischaemic effect. Such a direct effect is unlikely to be related to activation of the degradation products of the arachidonic acid cascade since it was not influenced by indomethacin.
研究目的——确定7-氧代前列环素对早期闭塞后再灌注心律失常的长期保护作用是仅由于抗缺血作用，还是与直接膜效应相结合。设计——本研究在电刺激的离体兔乳头肌标本上进行，标本分别孵育或不孵育稳定的前列环素类似物7-氧代前列环素麻黄碱（7-氧代-PgI2）。在一些实验中，兔子用7-氧代-PgI2预处理。测量和结果——与1.1×10⁻⁸摩尔/升的7-氧代-PgI2孵育20分钟并随后冲洗后2小时，动作电位持续时间（APD90）和有效不应期显著延长。如果在整个实验过程中维持与7-氧代-PgI2的孵育，情况也是如此。唯一的其他变化是动作电位幅度略有减小。在20分钟的孵育期内，APD90和有效不应期均未受影响，仅观察到去极化最大速率的短暂增加，冲洗后消失。在4小时的观察期内，对照标本没有变化。7-氧代-PgI2诱导的长期电生理变化不受与2.8×10⁻⁶摩尔/升消炎痛孵育60分钟的影响。在实验前48小时，给兔子肌肉注射50微克/千克的7-氧代-PgI2进行预处理，与未处理的对照组相比，有效不应期延长。结论——7-氧代-PgI2可使充分氧合的正常乳头肌以及缺血心脏中的APD90和有效不应期延长。因此，直接膜效应可能有助于其抗心律失常作用，以及间接抗缺血作用。这种直接效应不太可能与花生四烯酸级联反应的降解产物的激活有关，因为它不受消炎痛的影响。
