[Cardioprotective effects of flokalin: relative role of activation of sarcolemmal and mitochondrial adenosine triphosphate-dependent potassium channels].
In experiments on isolated Langendorff perfused hearts of guinea pig with modeling of ischemia (20 min) and reperfusion (40 min) the cardioprotective effects of flokalin were shown. Preliminary preischemic perfusion of isolated heart with flokalin (5 mM) for 5 minutes has significantly improved the recovery of contractive function ofischemic myocardium at repcrfusion. Particularly, recovery of systolic and developed pressure was improved and the increasing of end-diastolic pressure in left ventricle was prevented. The vasoconstriction of coronary vessels was prevented and number of extrasystols at reperfusion of ischemic heart was decreased. Morphological studies have shown that flokalin prevents the significant damage of myocardial structure and the development of hypercontraction of myofibrils at ischemia-reperfusion of myocardium. It also preserves the intact sarcolemma and intracellular organelles. The intact structure of mitochondria also was saved by flokalin that maintains the energy potential of myocardium. Using the selective blocker of mitochondrial K(ATP) channels 5-hydroxydecanoate (200 mM) allows to determine the relative role of sarcolemmal and mitochondrial K(ATP) channels activation in these effects. It was shown that mitochondrial as well as sarcolemmal K(ATP) channels play role in the recovery of ischemic myocardium functions: first are responsible for recovery of contractive function and second are responsible for coronary blood flow recovery.
Strutyns'kyĭ
R B
RB
Pyvovar
S M
SM
Tumanovs'ka
L V
LV
Moĭbenko
O O
OO
D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology*; D003652:Decanoic Acids / Q000494:pharmacology; D006168:Guinea Pigs; D006880:Hydroxy Acids / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008929:Mitochondria, Heart / Q000378:metabolism* / Q000648:ultrastructure; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D020110:Pinacidil / Q000031:analogs & derivatives* / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000378:metabolism*; D012508:Sarcolemma / Q000378:metabolism* / Q000648:ultrastructure
D002316:Cardiotonic Agents; D003652:Decanoic Acids; D006880:Hydroxy Acids; C559719:N-(4-difluoromethoxyphenyl)-N'-pinacolyl-N''-cyanoguanidine; D026902:Potassium Channel Blockers; D015221:Potassium Channels; C117780:mitochondrial K(ATP) channel; C052853:5-hydroxydecanoic acid; D020110:Pinacidil