Permissive effect of molsidomine towards cardioprotective action of iloprost in myocardial ischemia in cats.
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.(ABSTRACT TRUNCATED AT 250 WORDS)
Gryglewski
R J
RJ
Department of Pharmacology, Jagiellonian University School of Medicine, Kraków, Poland.
Swies
J
J
Chłopicki
S
S
Niezabitowski
P
P
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002415:Cats; D004357:Drug Synergism; D005260:Female; D006352:Heart Ventricles / Q000187:drug effects*; D016285:Iloprost / Q000494:pharmacology*; D008297:Male; D008981:Molsidomine / Q000494:pharmacology*; D009200:Myocardial Contraction / Q000187:drug effects; D017202:Myocardial Ischemia / Q000188:drug therapy*
D008981:Molsidomine; D016285:Iloprost