BackgroundAging involves reductions in exercise total limb blood flow and exercise capacity. We hypothesized that this may involve early age-related impairments of skeletal muscle microvascular responsiveness as previously reported for insulin but not for exercise stimuli in humans.MethodsUsing an isometric exercise model, we studied the effect of age on contrast-enhanced ultrasound (CEUS) parameters, i.e. microvascular blood volume (MBV), flow velocity (MFV) and blood flow (MBF) calculated from replenishment of Sonovue contrast-agent microbubbles after their destruction. CEUS was applied to the vastus lateralis (VLat) and intermedius (VInt) muscle in 15 middle-aged (MA, 43.6±1.5 years) and 11 young (YG, 24.1±0.6 years) healthy males before, during, and after 2 min of isometric knee extension at 15% of peak torque (PT). In addition, total leg blood flow as recorded by femoral artery Doppler-flow. Moreover, fiber-type-specific and overall capillarisation as well as fiber composition were additionally assessed in Vlat biopsies obtained from CEUS site. MA and YG had similar quadriceps muscle MRT-volume or PT and maximal oxygen uptake as well as a normal cardiovascular risk factors and intima-media-thickness.ResultsDuring isometric exercise MA compared to YG reached significantly lower levels in MFV (0.123±0.016 vs. 0.208±0.036 a.u.) and MBF (0.007±0.001 vs. 0.012±0.002 a.u.). In the VInt the (post-occlusive hyperemia) post-exercise peaks in MBV and MBF were significantly lower in MA vs. YG. Capillary density, capillary fiber contacts and femoral artery Doppler were similar between MA and YG.ConclusionsIn the absence of significant age-related reductions in capillarisation, total leg blood flow or muscle mass, healthy middle-aged males reveal impaired skeletal muscle microcirculatory responses to isometric exercise. Whether this limits isometric muscle performance remains to be assessed.

Obstructive sleep apnea (OSA) independent of obesity (OBS) imposes severe cardiovascular risk. To what extent plasma cystine concentration (CySS), a novel pro-oxidative vascular risk factor, is increased in OSA with or without OBS is presently unknown. We therefore studied CySS together with the redox state and precursor amino acids of glutathione (GSH) in peripheral blood mononuclear cells (PBMC) in untreated male patients with OSA (apnea-hypopnea-index (AHI) > 15 h−1, n = 28) compared to healthy male controls (n = 25) stratifying for BMI ≥ or < 30 kg m−2. Fifteen OSA patients were reassessed after 3–5-months CPAP. CySS correlated with cumulative time at an O2-saturation <90% (Tu90%) (r = 0.34, p < 0.05) beside BMI (r = 0.58, p < 0.001) and was higher in subjects with “hypoxic stress” (59.4 ± 2.0 vs. 50.1 ± 2.7 µM, p < 0.01) defined as Tu90% ≥ 15.2 min (corresponding to AHI ≥ 15 h−1). Moreover, CySS significantly correlated with systolic (r = 0.32, p < 0.05) and diastolic (r = 0.31, p < 0.05) blood pressure. CPAP significantly lowered CySS along with blood pressure at unchanged BMI. Unexpectedly, GSH antioxidant capacity in PBMC was increased with OSA and reversed with CPAP. Plasma CySS levels are increased with OSA-related hypoxic stress and associated with higher blood pressure. CPAP decreases both CySS and blood pressure. The role of CySS in OSA-related vascular endpoints and their prevention by CPAP warrants further studies.

Obstructive sleep apnea (OSA), independently of obesity (OBS), predisposes to insulin resistance (IR) for largely unknown reasons. Since OSA-related intermittent hypoxia triggers lipolysis, overnight increases in circulating free fatty acid (FFA) including palmitic acid (PA) may lead to ectopic intramuscular lipid accumulation potentially contributing to IR. Using 3-T-1H-magnetic-resonance-spectroscopy, we therefore compared intra- and extra-myocellular lipid (IMCL and EMCL) in vastus lateralis muscle at ~7:00 a.m. between 26 male patients with moderate-to-severe OSA (17 obese, 9 non-obese) and 23 healthy male controls (12 obese, 11 non-obese). Fiber type composition was evaluated by muscle biopsies. Moreover, we measured fasted FFA including PA, HbA1c, thigh subcutaneous fat volume (ScFAT, 1.5-T-magnetic-resonance-tomograpphy) and maximal oxygen uptake (VO2max). 14 patients were reassessed after continuous-positive-airway-pressure (CPAP) therapy. Total FFA and PA were significantly by 178% and 166% higher in OSA patients vs. controls and correlated with the apnea-hypopnea index (AHI) (r≥0.45, P&lt;0.01). Moreover, IMCL and EMCL were 55% (P&lt;0.05) and 40% (P&lt;0.05) higher in OSA patients, i.e. 114% and 103% in non-obese, 24.4% and 8.4% in obese subjects (with higher control levels). Overall, PA, FFA (minus PA) and ScFAT significantly contributed to IMCL (multiple r=0.568, P=0.002). CPAP significantly decreased EMCL (-26%) and, by trend only, IMCL, total FFA and PA. Muscle fiber composition was unaffected by OSA or CPAP. Increases in IMCL and EMCL are detectable at ~7:00 a.m. in OSA patients and partly attributable to overnight FFA excesses and high ScFAT or BMI. CPAP decreases FFAs and IMCL by trend but significantly reduces EMCL.