Protection against ischemia-induced ventricular arrhythmias and myocardial dysfunction conferred by preconditioning in the rat heart: involvement of mitochondrial K(ATP) channels and reactive oxygen species
Language English Country Czech Republic Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
18198991
DOI
10.33549/physiolres.931317
PII: 1317
Knihovny.cz E-resources
- MeSH
- Acetylcysteine pharmacology MeSH
- Anti-Arrhythmia Agents pharmacology MeSH
- Antioxidants pharmacology MeSH
- Potassium Channel Blockers pharmacology MeSH
- Time Factors MeSH
- Diazoxide pharmacology MeSH
- Potassium Channels drug effects metabolism MeSH
- Ventricular Function, Left * drug effects MeSH
- Hydroxy Acids pharmacology MeSH
- Ischemic Preconditioning, Myocardial * MeSH
- Ventricular Premature Complexes metabolism physiopathology prevention & control MeSH
- Myocardial Contraction * drug effects MeSH
- Rats MeSH
- Decanoic Acids pharmacology MeSH
- Thiobarbituric Acid Reactive Substances metabolism MeSH
- Myocardium metabolism MeSH
- Recovery of Function MeSH
- Oxidative Stress MeSH
- Perfusion MeSH
- Lipid Peroxidation MeSH
- Rats, Wistar MeSH
- Reactive Oxygen Species metabolism MeSH
- Myocardial Reperfusion Injury metabolism physiopathology prevention & control MeSH
- In Vitro Techniques MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- 5-hydroxydecanoic acid MeSH Browser
- Acetylcysteine MeSH
- Anti-Arrhythmia Agents MeSH
- Antioxidants MeSH
- Potassium Channel Blockers MeSH
- Diazoxide MeSH
- Potassium Channels MeSH
- Hydroxy Acids MeSH
- Decanoic Acids MeSH
- Thiobarbituric Acid Reactive Substances MeSH
- mitochondrial K(ATP) channel MeSH Browser
- Reactive Oxygen Species MeSH
Ischemic preconditioning (I-PC) induced by brief episodes of ischemia and reperfusion (I/R) protects the heart against sustained I/R. Although activation of mitochondrial K(ATP) channels (mitoK(ATP)) interacting with reactive oxygen species (ROS) has been proposed as a key event in this process, their role in the antiarrhythmic effect is not clear. This study was designed: 1) to investigate the involvement of mito K(ATP) opening in the effect of I-PC (1 cycle of I/R, 5 min each) on ventricular arrhythmias during test ischemia (TI, 30-min LAD coronary artery occlusion) in Langendorff-perfused rat hearts and subsequent postischemic contractile dysfunction, and 2) to characterize potential mechanisms of protection conferred by I-PC and pharmacological PC induced by mito K(ATP) opener diazoxide (DZX), with particular regards to the modulation of ROS generation. Lipid peroxidation (an indicator of increased ROS production) was determined by measurement of myocardial concentration of conjugated dienes (CD) and thiobarbituric acid reactive substances (TBARS) in non-ischemic controls, non-preconditioned and preconditioned hearts exposed to TI, I-PC alone, as well as after pretreatment with DZX, mito K(ATP) blocker 5-hydroxydecanoate (5-HD) and antioxidant N-acetylcysteine (NAC). Total number of ventricular premature 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 an increase in CD and TBARS caused by ischemia indicating lower production of ROS. On the other hand, I-PC and DZX themselves moderately enhanced ROS generation, prior to TI. Bracketing of I-PC with 5-HD suppressed both, ROS production during PC and its cardioprotective effect. In conclusion, potential mechanisms of protection conferred by mito K(ATP) opening in the rat heart might involve a temporal increase in ROS production in the preconditioning phase triggering changes in the pro/antioxidant balance in the myocardium and attenuating ROS production during subsequent prolonged ischemia.
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