Bhargava A S, Preus M, Khater A R, Günzel P
Department of Experimental Toxicology, Schering Aktiengesellschaft, Berlin-West, Germany.
Arzneimittelforschung. 1990 Mar;40(3):248-52.
The effect of iloprost was investigated in an experimental model of cardiac damage in rats after isoprenaline (isoproterenol) treatment. Iloprost was administered by continuous subcutaneous infusion at a dose of 0.44 micrograms/kg body weight (b.w.)/min over a total period of 9 days. On day 8, 5 mg isoprenaline/kg b.w. was applied subcutaneously to induce the cardiac damage. The determinations of creatine kinase (CK, EC 2.7.3.2) and CK isoenzymes, lactate dehydrogenase (LDH, EC 1.1.1.27) and LDH isoenzymes as well as a-hydroxybutyrate dehydrogenase (a-HBDH, no EC) were performed 2, 6 and 24 h after isoprenaline application. Immediately after the last blood sampling, the animals were sacrificed and the hearts were examined histologically. Iloprost-pretreated animals showed a reduction in the rise in heart-specific isoenzymes CK-MB and LDH1-3 in the serum after isoprenaline application. A decrease in isoenzymes CK-BB and LDH4-5 in the serum was also observed in iloprost-pretreated rats. However, no difference could be detected histologically in the extent of myocardial necrosis between animals treated with isoprenaline alone or in combination with iloprost. These results suggest a biochemical cardioprotective effect of iloprost in this rat model after isoprenaline application and the lack of correlation with histological findings is discussed.
在异丙肾上腺素治疗后的大鼠心脏损伤实验模型中研究了伊洛前列素的作用。伊洛前列素通过皮下持续输注给药,剂量为0.44微克/千克体重(b.w.)/分钟,共持续9天。在第8天,皮下注射5毫克异丙肾上腺素/千克b.w.以诱导心脏损伤。在应用异丙肾上腺素后2、6和24小时测定肌酸激酶(CK,EC 2.7.3.2)及其同工酶、乳酸脱氢酶(LDH,EC 1.1.1.27)及其同工酶以及α-羟丁酸脱氢酶(α-HBDH,无EC)。在最后一次采血后立即处死动物,并对心脏进行组织学检查。伊洛前列素预处理的动物在应用异丙肾上腺素后血清中心脏特异性同工酶CK-MB和LDH1-3的升高有所降低。在伊洛前列素预处理的大鼠中还观察到血清中同工酶CK-BB和LDH4-5的降低。然而,在单独用异丙肾上腺素治疗或与伊洛前列素联合治疗的动物之间,在心肌坏死程度的组织学检查中未检测到差异。这些结果表明伊洛前列素在应用异丙肾上腺素后的该大鼠模型中具有生化心脏保护作用,并讨论了其与组织学结果缺乏相关性的问题。