Jacobs, Kevin A., Jochen Kressler, Mark Stoutenberg, Bernard A. Roos, and Anne L. Friedlander. Sildenafil has little influence on cardiovascular hemodynamics or 6-km time trial performance in trained men and women at simulated high altitude. High Alt. Med. Biol. 12: 215–222, 2011.—Sildenafil improves maximal exercise capacity at high altitudes (∼4350–5800 m) by reducing pulmonary arterial pressure and enhancing oxygen delivery, but the effects on exercise performance at less severe altitudes are less clear. Purpose: To determine the effects of sildenafil on cardiovascular hemodynamics (heart rate, stroke volume, and cardiac output), arterial oxygen saturation (Sa_O2), and 6-km time-trial performance of endurance-trained men and women at a simulated altitude of ∼3900 m. Methods: Twenty men and 15 women, endurance-trained, completed one experimental exercise trial (30 min at 55% of altitude-specific capacity +6-km time trial) at sea level (SL) and two trials at simulated high altitude (HA) while breathing hypoxic gas (12.8% F_Io₂) after ingestion of either placebo or 50 mg sildenafil in double-blind, randomized, and counterbalanced fashion. Results: Maximal exercise capacity and Sa_O2 were significantly reduced at HA compared to SL (18%–23%), but sildenafil did not significantly improve cardiovascular hemodynamics or time-trial performance in either men or women compared to placebo and only improved Sa_O2 in women (4%). One male subject (5% of male subjects, 2.8% of all subjects) exhibited a meaningful 36-s improvement in time-trial performance with sildenafil compared to placebo. Conclusions: In this group of endurance trained men and women, sildenafil had very little influence on cardiovascular hemodynamics, Sa_O2, and 6-km time-trial performance at a simulated altitude of ∼3900 m. It appears that a very small percentage of endurance-trained men and women derive meaningful improvements in aerobic performance from sildenafil at a simulated altitude of ∼3900 m.

This study examined the effect of moderate intensity stair stepping exercise on the glycemic response, and antioxidant capacity (TAC) during an oral glucose tolerance test (OGTT). Thirty participants (women = 12) completed 4 OGTTs during rest or stair walking bouts of 1, 3, and 10 min in a randomized order. Blood was collected at baseline and 30 min during the OGTTs and analyzed for glucose, insulin, TAC, and lactate. Glucose concentrations were decreased following the 10 min (-22.69 (-34.66 to -10.72) mg/dL, p < 0.002) and 3 min (-15.37 (-25.05 to -5.69) mg/dL, p < 0.004) bouts but not the 1 min bout (-6.18 (-19.54 to 7.18) mg/dL, p = 0.352). Insulin concentrations were decreased following the 10 min (-6.11 (-8.86 to -3.36 μIU/dL), p < 0.001) and 3 min (-2.589 (-4.54 to -0.63) μIU/dL, p < 0.012) bouts but not the 1 min bout (-0.37 (-1.87 to 1.13) μIU/dL, p = 0.616). Insulin sensitivity index values showed a significant increase in the 10-min trial (1.81 (0.03-3.58), p < 0.048), but not during the 3 min (0.65 (-0.66 to 1.96) p = 0.317) or 1 min trial (0.13 (-1.58 to 1.84) p = 0.878). There was no omnibus effect for trial in TAC (p = 0.132, η² = 0.07). There was no interaction between trial and time for blood lactate (p = 0.621, η² = 0.02). This study provides evidence bouts as short as 3 min decrease postprandial blood glucose and insulin levels but longer bouts are needed to affect insulin sensitivity.

Introduction: Because impaired excitation‐contraction coupling and reduced sarcoplasmic reticulum (SR) Ca²⁺release may contribute to the age‐associated decline in skeletal muscle strength, we investigated the effect of aging on regulation of the skeletal muscle isoform of the ryanodine receptor (RyR1) by physiological channel ligands.Methods: [³H]Ryanodine binding to membranes from 8‐ and 26‐month‐old Fischer 344 extensor digitorum longus (EDL) and soleus muscles was used to investigate the effects of age on RyR1 modulation by Ca²⁺and calmodulin (CaM).Results: Aging reduced maximal Ca²⁺‐stimulated binding to EDL membranes. In 0.3 μM Ca²⁺, age reduced binding and CaM increased binding to EDL membranes. In 300 μM Ca²⁺, CaM reduced binding, but the age effect was not significant. Aging did not affect Ca²⁺or CaM regulation of soleus RyR1.Discussion: In aged fast‐twitch muscle, impaired RyR1 Ca²⁺regulation may contribute to lower SR Ca²⁺release and reduced muscle function.Muscle Nerve57: 1022–1025, 2018