Journal article
Ischemia reperfusion injury, KATP channels, and exercise-induced cardioprotection against apoptosis
Journal of applied physiology (1985), Vol.113(3), pp.498-506
08/01/2012
Handle:
https://hdl.handle.net/2376/107361
PMCID: PMC3426170
PMID: 22653992
Abstract
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.
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Details
- Title
- Ischemia reperfusion injury, KATP channels, and exercise-induced cardioprotection against apoptosis
- Creators
- John C Quindry - Cardioprotection Laboratory, Department of Kinesiology, Auburn University, Auburn, AlabamaLindsey Miller - Cardioprotection Laboratory, Department of Kinesiology, Auburn University, Auburn, AlabamaGraham McGinnis - Cardioprotection Laboratory, Department of Kinesiology, Auburn University, Auburn, AlabamaBrian Kliszczewicz - Cardioprotection Laboratory, Department of Kinesiology, Auburn University, Auburn, AlabamaJ. Megan Irwin - Department of Health, Leisure, and Exercise Science, Appalachian State University, Boone, North Carolina; andMichael Landram - Department of Health, Leisure, and Exercise Science, Appalachian State University, Boone, North Carolina; andZea Urbiztondo - Department of Health, Leisure, and Exercise Science, Appalachian State University, Boone, North Carolina; andGayani Nanayakkara - Harrison School of Pharmacy, Auburn University, Auburn, AlabamaRajesh Amin - Harrison School of Pharmacy, Auburn University, Auburn, Alabama
- Publication Details
- Journal of applied physiology (1985), Vol.113(3), pp.498-506
- Publisher
- American Physiological Society; Bethesda, MD
- Identifiers
- 99900546767801842
- Language
- English
- Resource Type
- Journal article