Ischemia reperfusion injury, KATP channels, and exercise-induced cardioprotection against apoptosis

John C. Quindry, Lindsey Miller, Graham McGinnis, Brian Kliszczewicz, J. Megan Irwin, Michael Landram, Zea Urbiztondo, Gayani Nanayakkara, Rajesh Amin

Research output: Contribution to journalArticlepeer-review

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 KATP or sarc KATP, 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 KATP 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 KATP 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 KATP (P = 0.177) nor sarc KATP (P = 0.274) channel provided post-IR protection against apoptosis (terminal deoxynucleotidyl transferase deoxy UTPmediated nick-end labeling-positive nuclei/mm2, 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.

Original languageEnglish
Pages (from-to)498-506
Number of pages9
JournalJournal of Applied Physiology
Volume113
Issue number3
DOIs
StatePublished - Aug 1 2012

Keywords

  • Autophagy
  • Heart disease
  • Infarction
  • Myocardial
  • Preconditioning

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