Permissive effect of molsidomine towards cardioprotective action of iloprost in myocardial ischemia in cats
Gryglewski, R.J.; Swies, J.; Chłopicki, S.; Niezabitowski, P.
Journal of Physiology and Pharmacology An Official Journal of the Polish Physiological Society 44(3): 313-318
1993
ISSN/ISBN: 0867-5910 PMID: 7694690 Document Number: 413338
Molsidomine, a donor of nitric oxide, is a drug used in the treatment of ischaemic heart disease. Iloprost, a stable analogue of prostacyclin, is a cardioprotective agent in dogs, cats and rats but not in men. We have studied an interaction between molsidomine and iloprost in protecting against consequences of the "no-reperfusion" myocardial ischaemia. In ten control open-chest cats the left descending coronary artery (LDCA) was ligated at a site of its branching. This procedure caused 80% of mortality and the survival time was 40.9 +/- 8.6 min. The death of cats was preceded by continuous premature ventricular contractions (PVC) which appeared 2.1 +/- 0.3 min after LDCA and occurred with frequency of 7.3 +/- 0.6 per min. Molsidomine at a dose of 20 micrograms/kg i.v. given to ten cats before LDCA was neither cardioprotective nor it influenced the rate of mortality while iloprost at a dose of 2 micrograms/kg i.v. opposed the outcome of LDCA as alluded by the elongation of the survival time to 66.6 +/- 7.6 min and the delay of the onset of PVC to 9.1 +/- 1.9 min; also the frequency of PVC fell to 3.6 +/- 0.4 per min, however, the LDCA-induced mortality (60%) was not significantly different from that in control animals (80%). On the other hand, in ten cats with LDCA which were pretreated with a mixture of molsidomine and iloprost there was observed a significant reduction of the LDCA-induced mortality (down to 20%) and a two fold increase in the survival time. Thereby, we conclude that molsidomine permitted enhancing the cardioprotective potency of iloprost.