Document Detail

Ischemia reperfusion injury, KATP channels, and exercise-induced cardioprotection against apoptosis.
MedLine Citation:
PMID:  22653992     Owner:  NLM     Status:  MEDLINE    
Exercise is a potent stimulus against cardiac ischemia reperfusion (IR) injury, although the protective mechanisms are not completely understood. The study purpose was to examine whether the mitochondrial or sarcolemmal ATP-sensitive potassium channel (mito K(ATP) or sarc K(ATP), respectively) mediates exercise-induced cardioprotection against post-IR cell death and apoptosis. Eighty-six, 4-mo-old male Sprague Dawley rats were randomly assigned to treadmill exercise (Ex; 30 m/min, 3 days, 60 min, ∼70 maximal oxygen uptake) and sedentary (Sed) treatments. Rats were exposed to regional cardiac ischemia (50 min) and reperfusion (120 min) or Sham (170 min; no ligation) surgeries. Exercise subgroups received placebo (saline), 5-hydroxydecanoate (5HD; 10 mg/kg ip), or HMR1098 (10 mg/kg ip) to inhibit mito K(ATP) or sarc K(ATP) channel. Comprehensive outcome assessments included post-IR ECG arrhythmias, cardiac tissue necrosis, redox perturbations, and autophagy biomarkers. No arrhythmia differences existed between exercised and sedentary hearts following extended-duration IR (P < 0.05). The sarc K(ATP) channel was confirmed essential (P = 0.002) for prevention of antinecrotic tissue death with exercise (percent infarct, Sed = 42%; Ex = 20%; Ex5HD = 16%; ExHMR = 42%), although neither the mito K(ATP) (P = 0.177) nor sarc K(ATP) (P = 0.274) channel provided post-IR protection against apoptosis (terminal deoxynucleotidyl transferase deoxy UTP-mediated nick-end labeling-positive nuclei/mm(2), Sham = 1.8 ± 0.5; Sed = 19.4 ± 6.7; Ex = 7.5 ± 4.6; Ex5HD = 14.0 ± 3.9; ExHMR = 11.1 ± 1.8). Exercise preconditioning also appears to preserve basal autophagy levels, as assessed by Beclin 1 (P ≤ 0.001), microtubule-associated protein-1 light-chain 3B ratios (P = 0.020), and P62 (P ≤ 0.001), in the hours immediately following IR. Further research is needed to better understand these findings and corresponding redox changes in exercised hearts.
John C Quindry; Lindsey Miller; Graham McGinnis; Brian Kliszczewicz; J Megan Irwin; Michael Landram; Zea Urbiztondo; Gayani Nanayakkara; Rajesh Amin
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-05-31
Journal Detail:
Title:  Journal of applied physiology (Bethesda, Md. : 1985)     Volume:  113     ISSN:  1522-1601     ISO Abbreviation:  J. Appl. Physiol.     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-08-02     Completed Date:  2013-01-08     Revised Date:  2013-09-26    
Medline Journal Info:
Nlm Unique ID:  8502536     Medline TA:  J Appl Physiol (1985)     Country:  United States    
Other Details:
Languages:  eng     Pagination:  498-506     Citation Subset:  IM    
Cardioprotection Laboratory, Department of Kinesiology, Auburn University, Auburn, Alabama 36830, USA.
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MeSH Terms
Anti-Arrhythmia Agents / pharmacology
Apoptosis / drug effects,  physiology*
Apoptosis Regulatory Proteins / analysis
Autophagy / physiology
Decanoic Acids / pharmacology
Glucuronides / pharmacology
Hydroxy Acids / pharmacology
KATP Channels / antagonists & inhibitors,  physiology*
Microtubule-Associated Proteins / analysis
Mitochondria, Heart / drug effects,  physiology
Myocardial Reperfusion Injury / drug therapy,  physiopathology,  prevention & control*
Oxygen Consumption / drug effects,  physiology
Physical Conditioning, Animal / physiology*
Rats, Sprague-Dawley
Sarcolemma / drug effects,  physiology
Sulfonamides / pharmacology
Transcription Factors / analysis
Grant Support
Reg. No./Substance:
0/Anti-Arrhythmia Agents; 0/Apoptosis Regulatory Proteins; 0/Decanoic Acids; 0/Glucuronides; 0/Gtf2h1 protein, mouse; 0/HMR 1098 glucuronide; 0/Hydroxy Acids; 0/KATP Channels; 0/MAP1LC3 protein, mouse; 0/Microtubule-Associated Proteins; 0/Sulfonamides; 0/Transcription Factors; 0/beclin 1 protein, rat; 624-00-0/5-hydroxydecanoic acid

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