Tosaki A, Koltai M, Paubert-Braquet M
Department of Pharmacology, Albert Szent-Györgyi University Medical School of Szeged, Hungary.
Eur J Pharmacol. 1990 Nov 20;191(1):69-81. doi: 10.1016/0014-2999(90)94097-h.
Isolated hearts excised from normotensive (NT) and spontaneously hypertensive (SH) rats subjected to transient normothermic global ischemia were used to study the effect of chronic treatment with iloprost on reperfusion-induced arrhythmias and myocardial ion shifts. After 30 min of ischemia, iloprost given s.c. in doses of 10, 50, 100 and 200 micrograms/kg per day for 14 days reduced the incidence of reperfusion-induced ventricular fibrillation (VF) in isolated hearts from the control value of 91 to 83, 75, 50 (P less than 0.05) and 25% (P less than 0.01) respectively, in NT rats. In the SH groups, the incidence of VF was also reduced from 100 to 75, 58, 33 (P less than 0.01) and 17% (P less than 0.001), respectively, with 10, 50, 100 and 200 micrograms/kg per day of iloprost. A similar reduction was observed in the incidence of reperfusion-induced ventricular tachycardia (VT). Ischemia and reperfusion caused significant changes in myocardial ion contents, i.e. an increase in Na+ and Ca2+ and a decrease in K+ and Mg2+ concentrations. The myocardial water content was also increased in parallel to the Na+ gain. The effect of iloprost given s.c. in doses of 50 and 200 micrograms/kg per day for 14 days was also measured on myocardial ion contents after 15- or 30-min ischemia and 30-min ischemia plus 10-min reperfusion. The higher iloprost dose significantly reduced the myocardial Na+, Ca2+ and water gains and the loss of K+ induced by ischemia and reperfusion in the NT and SH groups, while the decrease in Mg2+ content was alleviated only in SH rats. The results suggest that long-term iloprost treatment reduces the incidence of reperfusion-induced VF and VT by preventing Na+, Ca2+ and water accumulation as well as K+ and Mg2+ loss from myocardial tissue.
从正常血压(NT)大鼠和自发性高血压(SH)大鼠中取出的离体心脏,在经历短暂的常温全心缺血后,用于研究伊洛前列素长期治疗对再灌注诱导的心律失常和心肌离子变化的影响。缺血30分钟后,连续14天皮下注射剂量为10、50、100和200微克/千克/天的伊洛前列素,可使NT大鼠离体心脏中再灌注诱导的心室颤动(VF)发生率从对照值的91%分别降至83%、75%、50%(P<0.05)和25%(P<0.01)。在SH组中,每天给予10、50、100和200微克/千克伊洛前列素时,VF发生率也分别从100%降至75%、58%、33%(P<0.01)和17%(P<0.001)。在再灌注诱导的室性心动过速(VT)发生率上也观察到了类似的降低。缺血和再灌注导致心肌离子含量发生显著变化,即Na+和Ca2+增加,K+和Mg2+浓度降低。心肌含水量也与Na+增加平行升高。还测量了连续14天皮下注射剂量为50和200微克/千克/天的伊洛前列素对15分钟或30分钟缺血以及30分钟缺血加10分钟再灌注后心肌离子含量的影响。较高剂量的伊洛前列素显著降低了NT组和SH组中缺血和再灌注诱导的心肌Na+、Ca2+和水分增加以及K+丢失,而Mg2+含量的降低仅在SH大鼠中得到缓解。结果表明,长期伊洛前列素治疗通过防止心肌组织中Na+、Ca2+和水分积聚以及K+和Mg2+丢失,降低了再灌注诱导的VF和VT发生率。