title: Skeletal muscle microvascular oxygenation dynamics in heart failure: exercise training and nitric oxide-mediated function.
abstract: Chronic heart failure (CHF) impairs nitric oxide (NO)-mediated regulation of skeletal muscle O2 delivery-utilization matching such that microvascular oxygenation falls faster (i.e., speeds PO2mv kinetics) during increases in metabolic demand. Conversely, exercise training improves (slows) muscle PO2mv kinetics following contractions onset in healthy young individuals via NO-dependent mechanisms. We tested the hypothesis that exercise training would improve contracting muscle microvascular oxygenation in CHF rats partly via improved NO-mediated function. CHF rats (left ventricular end-diastolic pressure = 17 ± 2 mmHg) were assigned to sedentary (n = 11) or progressive treadmill exercise training (n = 11; 5 days/wk, 6-8 wk, final workload of 60 min/day at 35 m/min; -14% grade downhill running) groups. PO2mv was measured via phosphorescence quenching in the spinotrapezius muscle at rest and during 1-Hz twitch contractions under control (Krebs-Henseleit solution), sodium nitroprusside (SNP; NO donor; 300 μM), and N(G)-nitro-l-arginine methyl ester (L-NAME, nonspecific NO synthase blockade; 1.5 mM) superfusion conditions. Exercise-trained CHF rats had greater peak oxygen uptake and spinotrapezius muscle citrate synthase activity than their sedentary counterparts (p < 0.05 for both). The overall speed of the PO2mv fall during contractions (mean response time; MRT) was slowed markedly in trained compared with sedentary CHF rats (sedentary: 20.8 ± 1.4, trained: 32.3 ± 3.0 s; p < 0.05), and the effect was not abolished by L-NAME (sedentary: 16.8 ± 1.5, trained: 31.0 ± 3.4 s; p > 0.05). Relative to control, SNP increased MRT in both groups such that trained CHF rats had slower kinetics (sedentary: 43.0 ± 6.8, trained: 55.5 ± 7.8 s; p < 0.05). Improved NO-mediated function is not obligatory for training-induced improvements in skeletal muscle microvascular oxygenation (slowed PO2mv kinetics) following contractions onset in rats with CHF.
authors.affiliation: Department of Anatomy and Physiology, Kansas State University, Manhattan, Kansas;
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Hirai
authors.forename: Steven W
authors.initials: SW
authors.lastname: Copp
authors.forename: Clark T
authors.initials: CT
authors.lastname: Holdsworth
authors.forename: Scott K
authors.initials: SK
authors.lastname: Ferguson
authors.forename: Danielle J
authors.initials: DJ
authors.lastname: McCullough
authors.forename: Bradley J
authors.initials: BJ
authors.lastname: Behnke
authors.forename: Timothy I
authors.initials: TI
authors.lastname: Musch
authors.forename: David C
authors.initials: DC
authors.lastname: Poole
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D015415:Biomarkers / Q000097:blood; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005081:Exercise Therapy; D006333:Heart Failure / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D007700:Kinetics; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D009119:Muscle Contraction; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D010100:Oxygen / Q000097:blood*; D010101:Oxygen Consumption / Q000187:drug effects; D010807:Physical Endurance; D051381:Rats; D017207:Rats, Sprague-Dawley; D013318:Stroke Volume; D016277:Ventricular Function, Left; D017725:Ventricular Pressure
chemical_list: D015415:Biomarkers; D004791:Enzyme Inhibitors; D020030:Nitric Oxide Donors; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D010100:Oxygen
keywords: kinetics; microcirculation; myocardial infarction; oxygen delivery; oxygen utilization