Effect of endurance versus resistance training on local muscle and systemic inflammation and oxidative stress in COPD.

Limb muscle dysfunction in patients with COPD may be associated with local muscle and/or systemic inflammation, and therefore we investigated whether exercise training altered markers of inflammation and oxidative stress. We obtained vastus lateralis muscle biopsies and venous blood samples from patients with COPD (n = 30) before and after 8 weeks of resistance training (RT) (n = 15) or endurance training (ET) (n = 15). Healthy age-matched subjects were included as baseline controls (n = 8). Inflammatory markers in muscle and systemically were determined by interleukins (IL), tumour necrosis factor alfa (TNF-α), leukocyte concentration together with immunohistochemical staining for macrophages. Muscle oxidative stress and antioxidant capacity were determined by NADPH oxidase (NOX) and superoxide dismutase 2 (SOD2), respectively. Before exercise training, COPD patients had a higher muscular NOX protein content and circulating IL-8, IL-18, CRP, and leukocyte levels but a similar number of muscle-infiltrating macrophages compared with controls. Eight weeks of ET or RT increased muscle SOD2 content with no difference between groups. Plasma TNF-α, increased (P < .05) after ET and tended to (P = .06) increase after RT, but had no effect on muscular NOX protein content, number of muscle-infiltrating macrophages, or systemic levels of other pro-inflammatory cytokines or leukocytes. In patients with COPD, we found no evidence for muscular inflammation and no effect of exercise training. However, systemic inflammation was elevated in COPD and both training modalities induced an upregulation of muscle antioxidant capacity.

Muscle α-adrenergic responsiveness during exercise and ATP-induced vasodilation in chronic obstructive pulmonary disease patients.

Sympathetic vasoconstriction is blunted in exercising muscle (functional sympatholysis) but becomes attenuated with age. We tested the hypothesis that functional sympatholysis is further impaired in chronic obstructive pulmonary disease (COPD) patients. We determined leg blood flow and calculated leg vascular conductance (LVC) during 1) femoral-arterial Tyramine infusion (evokes endogenous norepinephrine release, 1 µmol·min-1·kg leg mass-1), 2) one-legged knee extensor exercise with and without Tyramine infusion [10 W and 20% of maximal workload (WLmax)], 3) ATP (0.05 µmol·min-1·kg leg mass-1) and Tyramine infusion, and 4) incremental ATP infusions (0.05, 0.3, and 3.0 µmol·min-1·kg leg mass-1). We included 10 patients with moderate to severe COPD and 8 age-matched healthy control subjects. Overall, leg blood flow and LVC were lower in COPD patients during exercise ( P < 0.05). Tyramine reduced LVC in both groups at 10-W exercise (COPD: -3 ± 1 ml·min-1·mmHg-1 and controls: -3 ± 1 ml·min-1·mmHg-1, P < 0.05) and 20% WLmax (COPD: -4 ± 1 ml·min-1·mmHg-1 and controls: -3 ± 1 ml·min-1·mmHg-1, P < 0.05) with no difference between groups. Incremental ATP infusions induced dose-dependent vasodilation with no difference between groups, and, in addition, the vasoconstrictor response to Tyramine infused together with ATP was not different between groups (COPD: -0.03 ± 0.01 l·min-1·kg leg mass-1 vs. CONTROLS: -0.04 ± 0.01 l·min-1·kg leg mass-1, P > 0.05). Compared with age-matched healthy control subjects, the vasodilatory response to ATP is intact in COPD patients and their ability to blunt sympathetic vasoconstriction (functional sympatholysis) as evaluated by intra-arterial Tyramine during exercise or ATP infusion is maintained. NEW & NOTEWORTHY The ability to blunt sympathetic vasoconstriction in exercising muscle and ATP-induced dilation in chronic obstructive pulmonary disease patients remains unexplored. Chronic obstructive pulmonary disease patients demonstrated similar sympathetic vasoconstriction in response to intra-arterial Tyramine during exercise and ATP-induced vasodilation compared with age-matched healthy control subjects.

Leg blood flow is impaired during small muscle mass exercise in patients with COPD.

Skeletal muscle blood flow is regulated to match the oxygen demand and dysregulation could contribute to exercise intolerance in patients with chronic obstructive pulmonary disease (COPD). We measured leg hemodynamics and metabolites from vasoactive compounds in muscle interstitial fluid and plasma at rest, during one-legged knee-extensor exercise, and during arterial infusions of sodium nitroprusside (SNP) and acetylcholine (ACh), respectively. Ten patients with moderate to severe COPD and eight age- and sex-matched healthy controls were studied. During knee-extensor exercise (10 W), leg blood flow was lower in the patients compared with the controls (1.82 ± 0.11 vs. 2.36 ± 0.14 l/min, respectively; P < 0.05), which compromised leg oxygen delivery (372 ± 26 vs. 453 ± 32 ml O2/min, respectively; P < 0.05). At rest, plasma endothelin-1 (vasoconstrictor) was higher in the patients with COPD (P < 0.05) and also tended to be higher during exercise (P = 0.07), whereas the formation of interstitial prostacyclin (vasodilator) was only increased in the controls. There was no difference between groups in the nitrite/nitrate levels (vasodilator) in plasma or interstitial fluid during exercise. Moreover, patients and controls showed similar vasodilatory capacity in response to both endothelium-independent (SNP) and endothelium-dependent (ACh) stimulation. The results suggest that leg muscle blood flow is impaired during small muscle mass exercise in patients with COPD possibly due to impaired formation of prostacyclin and increased levels of endothelin-1.NEW & NOTEWORTHY This study demonstrates that chronic obstructive pulmonary disease (COPD) is associated with a reduced blood flow to skeletal muscle during small muscle mass exercise. In contrast to healthy individuals, interstitial prostacyclin levels did not increase during exercise and plasma endothelin-1 levels were higher in the patients with COPD.

Alpha adrenergic receptor blockade increases capillarization and fractional O2 extraction and lowers blood flow in contracting human skeletal muscle.

AIM: To assess the effect of elevated basal shear stress on angiogenesis in humans and the role of enhanced skeletal muscle capillarization on blood flow and O2 extraction. METHODS: Limb haemodynamics and O2 extraction were measured at rest and during one-leg knee-extensor exercise (12 and 24 W) in 10 healthy untrained young men before and after 4-week treatment with an α1 receptor-antagonist (Terazosin, 1-2 mg day-1 ). Corresponding biopsies were taken from the m. vastus lateralis. RESULTS: Resting leg blood flow was increased by 57% 6 h following Terazosin treatment (P < 0.05), while basal capillary-to-fibre ratio was 1.69 ± 0.08 and increased to 1.90 ± 0.08 after treatment (P < 0.05). Leg O2 extraction during knee-extensor exercise was higher (4-5%; P < 0.05), leg blood flow and venous lactate levels lower (6-7%; P < 0.05), while leg VO2 was not different after Terazosin treatment. CONCLUSIONS: These results demonstrate that daily treatment with an α-adrenergic receptor blocker induces capillary growth in human skeletal muscle, likely due to increased shear stress. The increase in capillarization resulted in an increased fractional O2 extraction, a lower blood flow and venous lactate levels in the exercising leg. The increase in capillarization, and concomitant functional readouts in the exercising leg, may provide a basis for novel angiotherapy.