title: New approach to molsidomine active metabolites coming from the results of 2 models of experimental cardiology.
abstract: Molsidomine is a well-known vasodilatating, antianginal drug. Despite earlier studies with its metabolites (3-morpholino-syndnonimine (SIN-1) and N-nitroso-N-morpholino-amino-acetonitrile (SIN-1A)), which indicated a potential favorable cardioprotective activity, a lot of controversy remains. The aim of our research was to compare molsidomine, SIN-1, SIN-1A, and lidocaine influence on arrhythmias and hemodynamic parameters in 2 experimental models in rats. In the Langendorff heart study, SIN-1A markedly elevated left ventricular systolic pressure, maximum rise and fall of the first pressure derivative, coronary flow, and myocardial oxygen consumption. In addition, SIN-1A more so than SIN-1 significantly lowered creatine kinase release. The antiarrhythmic action of SIN-1 was observed, while lidocaine significantly diminished ventricular arrhythmias duration in comparison with the control. In the ischemia-reperfusion-induced arrhythmias model, hypotensive action of molsidomine was observed as well as the reduction in pressure rate product. Molsidomine also prolonged ventricular tachycardia duration. On the other hand, no significant effects on hemodynamic parameters as well as on ventricular arrhythmias were found in any of the SIN-1 and SIN-1A groups. In conclusion, our research suggests a possible direct, cardioprotective action of SIN-1A. It seems worthwhile to further investigate molsidomine derivatives, especially SIN-1A, because of its potential use in invasive cardiology procedures such as percutaneous transluminal coronary angioplasty.
authors.affiliation: a Chair and Department of Pharmacology, Medical University of Silesia, ul. Jordana 38, 41-808, Zabrze, Poland.
authors.forename: Michał
authors.initials: M
authors.lastname: Żorniak
authors.affiliation: b Silesian Centre for Heart Diseases, ul. Szpitalna 2, 41-800, Zabrze, Poland.
authors.forename: Katarzyna A
authors.initials: KA
authors.lastname: Mitręga
authors.affiliation: a Chair and Department of Pharmacology, Medical University of Silesia, ul. Jordana 38, 41-808, Zabrze, Poland.
authors.forename: Maurycy
authors.initials: M
authors.lastname: Porc
authors.affiliation: a Chair and Department of Pharmacology, Medical University of Silesia, ul. Jordana 38, 41-808, Zabrze, Poland.
authors.forename: Tadeusz F
authors.initials: TF
authors.lastname: Krzemiński
mesh_terms: D000818:Animals; D018927:Anti-Asthmatic Agents / Q000494:pharmacology; D001145:Arrhythmias, Cardiac / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D003402:Creatine Kinase / Q000378:metabolism; D004195:Disease Models, Animal; D006439:Hemodynamics / Q000187:drug effects*; D000067268:Isolated Heart Preparation; D008012:Lidocaine / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D008981:Molsidomine / Q000031:analogs & derivatives* / Q000494:pharmacology* / Q000627:therapeutic use; D009602:Nitrosamines / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D015427:Reperfusion Injury / Q000150:complications / Q000188:drug therapy / Q000378:metabolism
chemical_list: D018927:Anti-Asthmatic Agents; D009602:Nitrosamines; C006006:N-nitrosomorpholinoaminoacetonitrile; C002385:linsidomine; D008012:Lidocaine; D008981:Molsidomine; D003402:Creatine Kinase
keywords: Langendorff model; arrhythmias; arythmie; hemodynamic; hémodynamie; ischemia and reperfusion; ischémie et reperfusion; modèle de Langendorff; molsidomine metabolites; métabolites de la molsidomine; rat