Lindsey Miller

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

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.

Effect of resveratrol and quercetin supplementation on redox status and inflammation after exercise.

Resveratrol and quercetin function as antioxidants and anti-inflammatories in vitro, but these mechanisms have been minimally examined in combination in exercising humans. The purpose of this investigation was to examine supplementation as a countermeasure against oxidative stress and inflammation in response to exercise. Fourteen athletes were randomly assigned, in a double-blind crossover design, to a resveratrol and quercetin combination (RQ) (120 mg resveratrol and 225 mg quercetin for 6 days and 240 mg resveratrol and 450 mg quercetin on day 7 just prior to exercise) or to placebo (P). There was a 1-week washout between trials. Blood was taken at baseline, pre-exercise, immediately after exercise, and 1 h after exercise. Plasma was analyzed for oxidative stress (F2-isoprostanes and protein carbonyls), antioxidant capacity (ferric-reducing ability of plasma (FRAP), Trolox equivalent antioxidant capacity (TEAC), oxygen radical absorptive capacity (ORAC)), and inflammation (cytokine interleukin (IL)-8 and C-reactive protein (CRP)). Statistical design utilized a 2 × 3 ANOVA and Students t test. Pre-exercise values were not different from baseline for any measure. The postexercise increase in F2-isoprostanes was significantly less (p = 0.039 interaction) with RQ (68%) than with P (137%). Protein carbonyls, FRAP, ORAC, and TEAC significantly increased after exercise but were not affected by treatment. IL-8 and CRP increased significantly immediately after exercise but were not affected by treatment. These data indicate that RQ significantly reduces exercise-induced lipid peroxidation without associated changes in inflammation or plasma antioxidant status.

Evaluation of Arrhythmia Scoring Systems and Exercise-Induced Cardioprotection

INTRODUCTION Exercise is protective against ventricular arrhythmias induced by ischemia (I), the condition of inadequate blood flow, and reperfusion (R), the reestablishment of blood flow. This protection is observed clinically and scientifically by decreased incidence in ECG abnormalities. Numerous scoring systems exist for the quantification of ventricular arrhythmia severity. On the basis of preventricular contractions, ventricular tachycardia, and ventricular fibrillation frequency, these scoring systems are intended to provide more robust ECG outcome indicators than individual arrhythmia variables. Scoring systems vary primarily on continuous versus discontinuous treatment of the data, which should be considered when matching these arrhythmia metrics to scientific applications. PURPOSE The aim of this investigation was to evaluate seven ECG scoring systems in the assessment of ventricular arrhythmia severity after IR in male Sprague-Dawley rats. METHODS Animals remained sedentary or exercised (3 d of treadmill exercise for 60 min) before surgically induced IR. A subset of sedentary animals served as sham, undergoing surgical procedure without IR. ECGs were evaluated under blinded conditions by three trained individuals. Single arrhythmia data and the parametric score were analyzed by one-way ANOVA, whereas the Kruskal-Wallis was used to compare group means for all nonparametric scoring systems between groups. RESULTS IR produced a significant arrhythmic response in exercised and sedentary rats as determined by all arrhythmia scoring systems. Four arrhythmia metrics resulted in significant differences between exercised and sedentary treatments (P < 0.001), whereas three metrics did not. CONCLUSIONS Continuous versus discontinuous treatment of the data may account for variation in scoring system outcomes. These data confirm that exercise protects against IR-induced arrhythmias, and care must be taken when selecting an arrhythmia scoring system for ECG evaluation.