[Cardioprotective effects of activation of ATP-sensitive potassium channels in experiments in vivo: influence on blood biochemical parameters following ischemia-reperfusion of the myocardium].

Abstract

In experiments on the anaesthetized dogs with modeling of experimental ischemia (90 min) and reperfusion (180 min), the participation of biochemical processes in the cardioprotective effect of the preischemic activation of ATP-sensitive potassium (KATP) channels caused by intravenous introduction of flokalin, a new fluorine-containing opener of these channels was shown. Flokalin was introduced in a dose 0.1 mg/kg of animal body weight which practically did not change the parameters of hemodynamic in normoxia. Thus, the experiments investigating the influence offlokalin on changes of biochemical parameters of arterial blood during ischemia-reperfusion of myocardium showed certain features of ischemia-reperfusion syndrome development during stimulation of K(ATP) channels. The analysis of biochemical parameters of blood showed that flokalin suppressed free radical reactions and had antioxidant properties: reduced quantity of H2O2 and NO3- (the last can interpreted as a reduction in peroxynitrites formation), prevented the decline of catalase and superoxide dismutase activity. Practically constant content of low-molecular nitrosothiols in blood during all duration of experiment and increase of NO2-level during reperfusion may indicate on intact functions of the NO system and protective influence of flokalin during ischemia-reperfusion of myocardium. Practically unchanged content of inorganic phosphorus and uric acid in blood during ischemia- reperfusion under conditions of preischemic introduction of flokalin indicates the prevention of ATP degradation and fomation of both superoxide anion by xanthinoxidase and peroxynitrite by it interaction with nitric oxide. All mentioned properties of flokalin related to the changes of biochemical parameters of arterial blood, together with the changes of parameters of hemodynamics, result in diminishment of infarct size of myocardium after ischemia-reperfusion by 37% versus control experiments. K(ATP) channels, flokalin, ischemia-reperfusion, free radikaly, NO system.

• Authors: R B Strutyns'kyĭ, A V Kotsiuruba, O P Neshcheret, A M Shysh, R A Rovenets', O O Moĭbenko
• Journal: Fiziolohichnyi zhurnal (Kiev, Ukraine : 1994) (Fiziol Zh (1994)) Vol. 55 Issue 6 Pg. 12-9 ( 2009) ISSN: 2522-9028 [Print] Ukraine
• PMID: 20201384 (Publication Type: English Abstract, Journal Article)

Chemical References

• Antioxidants
• Cardiotonic Agents
• Free Radicals
• KATP Channels
• N-(4-difluoromethoxyphenyl)-N'-pinacolyl-N''-cyanoguanidine
• Uric Acid
• Phosphorus
• Pinacidil

Topics

• Animals
• Antioxidants (metabolism)
• Cardiotonic Agents (administration & dosage, pharmacology, therapeutic use)
• Disease Models, Animal
• Dogs
• Free Radicals (blood)
• Hemodynamics (drug effects)
• KATP Channels (metabolism)
• Myocardial Infarction (pathology, prevention & control)
• Myocardial Reperfusion Injury (blood, metabolism, pathology, physiopathology)
• Phosphorus (blood)
• Pinacidil (administration & dosage, analogs & derivatives, pharmacology, therapeutic use)
• Uric Acid (blood)