Open AccessProtection against ischemia-induced ventricular arrhythmias and myocardial dysfunction conferred by preconditioning in the rat heart: involvement of mitochondrial KATP channels and reactive oxygen species
Author(s) -
Jana Matějíková,
J Kucharská,
M Pintérová,
D Pancza,
T Ravíngerová
Publication year - 2009
Publication title -
physiological research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.647
H-Index - 70
eISSN - 1802-9973
pISSN - 0862-8408
DOI - 10.33549/physiolres.931317
Subject(s) - tbars , reactive oxygen species , ischemia , medicine , diazoxide , lipid peroxidation , chemistry , thiobarbituric acid , cardiology , ischemic preconditioning , pharmacology , oxidative stress , biochemistry , insulin
Ischemic preconditioning (I-PC) induced by brief episodes ofischemia and reperfusion (I/R) protects the heart againstsustained I/R. Although activation of mitochondrial KATP channels(mitoKATP) interacting with reactive oxygen species (ROS) hasbeen proposed as a key event in this process, their role in theantiarrhythmic effect is not clear. This study was designed: 1) toinvestigate the involvement of mito KATP opening in the effect ofI-PC (1 cycle of I/R, 5 min each) on ventricular arrhythmiasduring test ischemia (TI, 30-min LAD coronary artery occlusion)in Langendorff-perfused rat hearts and subsequent postischemiccontractile dysfunction, and 2) to characterize potentialmechanisms of protection conferred by I-PC and pharmacologicalPC induced by mito KATP opener diazoxide (DZX), with particularregards to the modulation of ROS generation. Lipid peroxidation(an indicator of increased ROS production) was determined bymeasurement of myocardial concentration of conjugated dienes(CD) and thiobarbituric acid reactive substances (TBARS) in nonischemic controls, non-preconditioned and preconditioned heartsexposed to TI, I-PC alone, as well as after pretreatment withDZX, mito KATP blocker 5-hydroxydecanoate (5-HD) andantioxidant N-acetylcysteine (NAC). Total number of ventricularpremature beats (VPB) that occurred in the control hearts(518±71) was significantly (P<0.05) reduced by I-PC (195±40),NAC (290±56) and DZX (168±22). I-PC and NAC suppressed anincrease in CD and TBARS caused by ischemia indicating lowerproduction of ROS. On the other hand, I-PC and DZX themselvesmoderately enhanced ROS generation, prior to TI. Bracketing ofI-PC with 5-HD suppressed both, ROS production during PC andits cardioprotective effect. In conclusion, potential mechanisms ofprotection conferred by mito KATP opening in the rat heart mightinvolve a temporal increase in ROS production in thepreconditioning phase triggering changes in the pro/antioxidantbalance in the myocardium and attenuating ROS productionduring subsequent prolonged ischemia.