VASCULAR KATP CHANNELS REDUCE SEVERE MUSCLE O2-DELIVERY TO O2-UTILIZATION MISMATCH DURING CONTRACTIONS IN CHRONIC HEART FAILURE RATS

Alexander J. Fees1, Clark T. Holdsworth1, Scott K. Ferguson1, Trenton D. Colburn1, David C. Poole1,2, & Timothy I. Musch1,2 1Department of Anatomy and Physiology, 2Department of Kinesiology, Kansas State University, Manhattan, KS, 66506, USA The vascular ATP-sensitive K+ (KATP) channel is a regulator of skeletal muscle microvascular O2 pressure (PO2mv; set by the O2-delivery to O2-utilization ratio) during contractions. Inadequate tissue PO2mv during exercise in chronic heart failure (CHF) constrains exercise capacity and may be exaggerated by KATP channel inhibition. PURPOSE: We tested the hypotheses that 1) KATP channel inhibition via glibenclamide (GLI), often prescribed for hyperglycemic CHF patients, would augment the PO2mv undershoot, increase the time to reach the steady-state PO2mv and decrease the mean PO2mv during contractions of the spinotrapezius muscle in CHF rats and 2) these effects would be reversed by the administration of pinacidil (PIN, KATP channel activator). METHODS: Muscle PO2mv was measured via the phosphorescence quenching technique during 180s of 1-Hz twitch contractions (~6 V) under control, GLI (5 mg/kg), and PIN (5 mg/kg) conditions in 16 male Sprague-Dawley rats with CHF induced via myocardial infarction (left main coronary artery ligation). RESULTS: GLI augmented the PO2mv undershoot (control: 2.3 ± 0.4, GLI: 4.1 ± 0.5 mmHg, p\u3c0.05) and time-to-reach contracting steady state (control: 66.1 ± 10.2, GLI: 93.6 ± 7.8 s, p\u3c0.05), and reduced baseline (control: 28.3 ± 0.9, GLI: 24.8 ± 1.0 mmHg, p\u3c0.05) and mean PO2mv (control: 20.6 ± 0.6, GLI: 17.6 ± 0.3 mmHg, p\u3c0.05). PIN reversed these effects of GLI (p\u3c0.05 for all) indicating that the primary effects of GLI were KATP channel specific. CONCLUSIONS: KATP channels protect against severe mismatch of muscle O2-delivery to O2-utilization during contractions in CHF rats. These data suggest that sulphonylurea therapy (e.g. GLI) poses an additional constraint to muscle O2 delivery in CHF patients and may further compromise physical activity; a contributing factor to morbidity and mortality

Schematic procedure Gene Expression and Genome CNA.

<p>Identification of up regulated genes with copy number gains and down regulated genes with copy number losses is showed.</p

G1 vs. G3 classification performances (mRNA and miRNA): specificity, cross-validation.

1<p>standard deviation.</p

Classification performance (mRNA and miRNA): AUC, TRAINING on G1*–G3P, TESTING on G1–G3.

1<p>standard deviation.</p

Schematic procedure miRNAs analysis.

<p>Combination of gene expression, genome CNA, and miRNA-regulated mRNAs.</p

USE OF SIT-TO- STAND WORKSTATIONS: IMPACT ON PHYSICAL ACTIVITY

Shiann Wickham, Catherine Patrick, Larissa Boyd, Melissa Powers University of Central Oklahoma, Edmond, Oklahoma Prolonged sitting affects daily total physical activity. Standing in order to break long periods of sitting may be beneficial to an individual’s health. PURPOSE: The purpose of this pilot study was to determine whether physical activity would change when using a sit-to-stand workstation in a workplace environment. METHOD: Volunteers from the faculty of the University of Central Oklahoma included apparently healthy male and female adults (N = 11, M = 39.09± 10.445 years). Participants were asked to use sit-to-stand workstations for a minimum of three hours per workday. The International Physical Activity Questionnaire (IPAQ) was used to measure self-reported daily physical activity. RESULTS: Dependent t-tests were used to analyze changes in self-reported physical activity over 5 months. Non-significant (p\u3e.05), meaningful improvements were seen in METmin/wk for walking (d=.19), total physical activity (d=.14), moderate activity (d=.01), and vigorous activity (d=.02). Total minutes of sit time per week (d=.25) and average daily minutes sitting (d=.25) decreased (p\u3e.05). CONCLUSION: Sit-to-stand workstations do provide an increase in daily physical activity levels. Although the results were non-significant, they do indicate a small decrease in time spent sitting along with small improvements in walking and total physical activity. Decreasing employee sitting time can increase the amount of physical activity achieved throughout the day. Future research should evaluate the use of sit-to-stand workstations in a larger, more diverse group of employees. See supplemental content for graphics

Log-Rank Test G1*vs G3*.

<p>Log-Rank Test G1*vs G3*.</p

Hazard ratio G3*vs G3.

<p>Hazard ratio G3*vs G3.</p

Heat maps for evaluation of our gene signatures in comparison with other gene signatures.

<p>III: combination of gene expression - genome CNA, and miRNA analysis, V: a down-sized gene signature (4 genes), Sotiriou et al. 97-gene signature, Ivshina et al. 18-gene signature and Ivshina et al. 6-gene signature. Classification performances were showed for: cross-validation (CV), and training on G1*–G3* - testing on G1–G3 (TT).</p

Classification performances: computational time (second) Mean per sample (execution time/number of samples).

<p>Intel Core i5-3330S CPU @ 2.70 GHz TRAINING-TEST.</p