The Effect of Pedaling Cadence on the Kinetics of Oxygen Uptake During Severe Intensity Exercise

During exhaustive severe intensity exercise, the oxygen uptake (VO2) increases exponentially, with a time constant of ~30 s. After ~1 to 2 min, a slow component emerges and drives the VO2 to its maximum. Pedaling cadence contributes to the metabolic demand at a given work rate and affects several responses to cycling exercise. PURPOSE: To determine the effect of pedaling cadence on parameters of the two-component VO2 response profile during severe intensity exercise. METHODS: Eight women (mean ± SD: age 22 ± 1 yr, height 161 ± 6 cm, and weight 58.8 ± 2.3 kg) and 10 men (age 23 ± 1 yr, height 180 ± 6 cm, and weight 82.9 ± 4.4 kg) performed exhaustive constant-power cycle ergometer tests using pedaling cadences of 60 rpm, 80 rpm, and 100 rpm. RESULTS: Times to exhaustion were smaller at higher cadences (220 ± 85 \u3c 299 ± 118 \u3c 368 ± 168 s), whereas VO2max values were the same at all cadences (2786 ± 729 = 2768 ± 749 = 2774 ± 732 ml/min). The mean response time of the primary response was faster at higher pedaling cadences (27 ± 5 \u3c 32 ± 5 \u3c 37 ± 5 s); the amplitude of the primary response was greater at the highest cadence (2045 ± 577 \u3e 1890 ± 493 = 1899 ± 515 ml/min); and the time delay before the slow component was smaller at higher cadences (85 ± 11 \u3c 105 ± 17 \u3c 118 ± 19 s). CONCLUSION: These results demonstrate that pedaling cadence affects the VO2 response profile. The higher cadences speed the primary or fundamental response and hasten the emergence of the slow component. This may have implications for the sport of cycling and should be considered when evaluating cardio-respiratory and metabolic responses to cycle ergometer exercise

The Effect of Work Rate on Oxygen Uptake Kinetics During Exhaustive Severe Intensity Cycling Exercise

The effect of work rate on oxygen uptake kinetics during exhaustive severe intensity cycling exercise Jennifer L. Sylvester, Samantha D. Burdette, Steven W. Cross, Nosa O. Idemudia, John, H. Curtis, Jakob L. Vingren, David W. Hill. Applied Physiology Laboratory, University of North Texas, Denton, TX During exhaustive severe intensity exercise, the oxygen uptake (VO2) increases exponentially, with a time constant of ~30 s. After ~1 to 2 min, a slow component emerges and drives the VO2 to its maximum. There are clear differences in the VO2 response profile across exercise intensity domains. These disparities might not be attributable to metabolic demand but, rather, to characteristics of the various intensity domains, such as the consequences of lactic acid production. PURPOSE: To investigate the role of exercise intensity on the VO2 response profile at intensities wholly within the severe domain. METHODS: Four women (mean ± SD: age 22 ± 2 years, height 167 ± 7 cm, mass 66 ± 5 kg) and eight men (age 23 ± 2 yr, height 179 ± 9 cm, mass 78 ± 10 kg) performed exhaustive constant-power cycle ergometer tests at two different severe intensity work rates (263 ± 78 W and 214 ± 64 W). Smoothed breath-by-breath VO2 data were fitted to a two-component (primary response and slow component) model using iterative regression. RESULTS: Times to exhaustion were 217 ± 27 s and 590 ± 82 s, respectively. The VO2max values were the same at the two different work rates (2973 ± 691 ml·min-1 and 3011 ± 728 ml·min-1). The amplitude of the primary response was greater (p \u3c 0.05) at the higher work rate (2095 ± 716 ml·min-1) than at the lower work rate (1857 ± 618 ml·min-1) and the amplitude of the slow component was smaller (367 ± 177 ml·min-1 vs 645 ± 347 ml·min-1). In addition, the time delay before the emergence of the slow component was shorter at the higher work rate (92 ± 22 s vs 116 ± 42 s). CONCLUSION: The results show that exercise intensity per se affects the VO2 response profile within the severe intensity domain and suggest that metabolic demand drives the primary response of VO2 kinetics within this domain. Category to be judged: Master\u27

Seizure reduction in TSC2-mutant mouse model by an mTOR catalytic inhibitor.

Tuberous sclerosis complex (TSC) is a neurodevelopmental disorder caused by autosomal-dominant pathogenic variants in either the TSC1 or TSC2 gene, and it is characterized by hamartomas in multiple organs, such as skin, kidney, lung, and brain. These changes can result in epilepsy, learning disabilities, and behavioral complications, among others. The mechanistic link between TSC and the mechanistic target of the rapamycin (mTOR) pathway is well established, thus mTOR inhibitors can potentially be used to treat the clinical manifestations of the disorder, including epilepsy.In this study, we tested the efficacy of a novel mTOR catalytic inhibitor (here named Tool Compound 1 or TC1) previously reported to be more brain-penetrant compared with other mTOR inhibitors. Using a well-characterized hypomorphic Tsc2 mouse model, which displays a translationally relevant seizure phenotype, we tested the efficacy of TC1.Our results show that chronic treatment with this novel mTOR catalytic inhibitor (TC1), which affects both the mTORC1 and mTORC2 signaling complexes, reduces seizure burden, and extends the survival of Tsc2 hypomorphic mice, restoring species typical weight gain over development.Novel mTOR catalytic inhibitor TC1 exhibits a promising therapeutic option in the treatment of TSC