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<0.05) and time-to-reach contracting steady state (control: 66.1 ± 10.2, GLI: 93.6 ± 7.8 s, p<0.05), and reduced baseline (control: 28.3 ± 0.9, GLI: 24.8 ± 1.0 mmHg, p<0.05) and mean PO2mv (control: 20.6 ± 0.6, GLI: 17.6 ± 0.3 mmHg, p<0.05). PIN reversed these effects of GLI (p<0.05 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.
Fees, AJ; Holdsworth, CT; Ferguson, SK; Colburn, TD; Poole, DC; and Musch, TI
"VASCULAR KATP CHANNELS REDUCE SEVERE MUSCLE O2-DELIVERY TO O2-UTILIZATION MISMATCH DURING CONTRACTIONS IN CHRONIC HEART FAILURE RATS,"
International Journal of Exercise Science: Conference Proceedings: Vol. 11
, Article 39.
Available at: https://digitalcommons.wku.edu/ijesab/vol11/iss4/39
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