The anaerobic threshold (AT) remains a widely recognized, and contentious, concept in exercise physiology and medicine. As conceived by Karlman Wasserman, the AT coalesced the increase of blood ...lactate concentration (La−), during a progressive exercise test, with an excess pulmonary carbon dioxide output (V̇CO2). Its principal tenets were: limiting oxygen (O2) delivery to exercising muscle→increased glycolysis, La− and H+ production→decreased muscle and blood pH→with increased H+ buffered by blood HCO3−→increased CO2 release from blood→increased V̇CO2 and pulmonary ventilation. This schema stimulated scientific scrutiny which challenged the fundamental premise that muscle anoxia was requisite for increased muscle and blood La−. It is now recognized that insufficient O2 is not the primary basis for lactataemia. Increased production and utilization of La− represent the response to increased glycolytic flux elicited by increasing work rate, and determine the oxygen uptake (V̇O2) at which La− accumulates in the arterial blood (the lactate threshold; LT). However, the threshold for a sustained non‐oxidative contribution to exercise energetics is the critical power, which occurs at a metabolic rate often far above the LT and separates heavy from very heavy/severe‐intensity exercise. Lactate is now appreciated as a crucial energy source, major gluconeogenic precursor and signalling molecule but there is no ipso facto evidence for muscle dysoxia or anoxia. Non‐invasive estimation of LT using the gas exchange threshold (non‐linear increase of V̇CO2 versus V̇O2) remains important in exercise training and in the clinic, but its conceptual basis should now be understood in light of lactate shuttle biology.
figure legend As originally posited and defended most ardently by Karlman Wasserman and Brian J. Whipp, the anaerobic threshold (AT) concept represents the epitome of integrative physiological control. The graph at the upper right portrays blood La−, arterial CO2 partial pressure (PCO2) and ventilation (V̇E) as a function of V̇O2 increasing from rest to maximum (V̇O2max). The AT is identified (black arrow) by the departure of V̇E from linearity without PCO2 decreasing. As shown rightwards from the ‘Original theory’ box, the AT held that lack of (or very low) muscle O2, via the Pasteur effect, increased muscle and blood lactic acid, then H+ dissociated from the lactic acid and was buffered by bicarbonate thus increasing CO2 evolution from the blood; this stimulated the ‘extra’ V̇E at AT simultaneous with the increase in La−. Currently we understand that neither anoxia nor dysoxia underpins increased muscle La− production and efflux, but rather its increase in the blood is attributed to the rate of La− appearance being greater than disappearance. Also, as long appreciated, the variability in, and complexities of, the control of breathing dictate that the V̇CO2 versus V̇O2 relation (gas exchange threshold) more reliably approximates the lactate threshold than does the ventilatory profile. At the bottom, the modern understanding of metabolism is that La− is a central element linking glycolysis (Gly) and oxidative phosphorylation (OxPhos) energetics. Via cell signalling, La− also plays roles in short‐ and long‐term adaptations in both health and disease.
The accumulation of dysfunctional mitochondria has been implicated in aging, but a deeper understanding of mitochondrial dynamics and mitophagy during aging is missing. Here, we show that ...upregulating Drp1-a Dynamin-related protein that promotes mitochondrial fission-in midlife, prolongs Drosophila lifespan and healthspan. We find that short-term induction of Drp1, in midlife, is sufficient to improve organismal health and prolong lifespan, and observe a midlife shift toward a more elongated mitochondrial morphology, which is linked to the accumulation of dysfunctional mitochondria in aged flight muscle. Promoting Drp1-mediated mitochondrial fission, in midlife, facilitates mitophagy and improves both mitochondrial respiratory function and proteostasis in aged flies. Finally, we show that autophagy is required for the anti-aging effects of midlife Drp1-mediated mitochondrial fission. Our findings indicate that interventions that promote mitochondrial fission could delay the onset of pathology and mortality in mammals when applied in midlife.Mitochondrial fission and fusion are important mechanisms to maintain mitochondrial function. Here, the authors report that middle-aged flies have more elongated, or 'hyper-fused' mitochondria, and show that induction of mitochondrial fission in midlife, but not in early life, extends the health and life of flies.
: The hyperbolic form of the power-duration relationship is rigorous and highly conserved across species, forms of exercise, and individual muscles/muscle groups. For modalities such as cycling, the ...relationship resolves to two parameters, the asymptote for power (critical power CP) and the so-called W' (work doable above CP), which together predict the tolerable duration of exercise above CP. Crucially, the CP concept integrates sentinel physiological profiles-respiratory, metabolic, and contractile-within a coherent framework that has great scientific and practical utility. Rather than calibrating equivalent exercise intensities relative to metabolically distant parameters such as the lactate threshold or V˙O2max, setting the exercise intensity relative to CP unifies the profile of systemic and intramuscular responses and, if greater than CP, predicts the tolerable duration of exercise until W' is expended, V˙O2max is attained, and intolerance is manifested. CP may be regarded as a "fatigue threshold" in the sense that it separates exercise intensity domains within which the physiological responses to exercise can (<CP) or cannot (>CP) be stabilized. The CP concept therefore enables important insights into 1) the principal loci of fatigue development (central vs. peripheral) at different intensities of exercise and 2) mechanisms of cardiovascular and metabolic control and their modulation by factors such as O2 delivery. Practically, the CP concept has great potential application in optimizing athletic training programs and performance as well as improving the life quality for individuals enduring chronic disease.
This document reviews 1) the measurement properties of commonly used exercise tests in patients with chronic respiratory diseases and 2) published studies on their utilty and/or evaluation obtained ...from MEDLINE and Cochrane Library searches between 1990 and March 2015.Exercise tests are reliable and consistently responsive to rehabilitative and pharmacological interventions. Thresholds for clinically important changes in performance are available for several tests. In pulmonary arterial hypertension, the 6-min walk test (6MWT), peak oxygen uptake and ventilation/carbon dioxide output indices appear to be the variables most responsive to vasodilators. While bronchodilators do not always show clinically relevant effects in chronic obstructive pulmonary disease, high-intensity constant work-rate (endurance) tests (CWRET) are considerably more responsive than incremental exercise tests and 6MWTs. High-intensity CWRETs need to be standardised to reduce interindividual variability. Additional physiological information and responsiveness can be obtained from isotime measurements, particularly of inspiratory capacity and dyspnoea. Less evidence is available for the endurance shuttle walk test. Although the incremental shuttle walk test and 6MWT are reliable and less expensive than cardiopulmonary exercise testing, two repetitions are needed at baseline. All exercise tests are safe when recommended precautions are followed, with evidence suggesting that no test is safer than others.
During high-intensity submaximal exercise, muscle fatigue and decreased efficiency are intertwined closely, and each contributes to exercise intolerance. Fatigue and muscle inefficiency share common ...mechanisms, for example, decreased "metabolic stability," muscle metabolite accumulation, decreased free energy of adenosine triphosphate breakdown, limited O2 or substrate availability, increased glycolysis, pH disturbance, increased muscle temperature, reactive oxygen species production, and altered motor unit recruitment patterns.
Muscle deoxygenation (i.e., deoxyHb + Mb) during exercise assesses the matching of oxygen delivery (Q̇O2) to oxygen utilization (V̇O2). Until now limitations in near-infrared spectroscopy (NIRS) ...technology did not permit discrimination of deoxyHb + Mb between superficial and deep muscles. In humans, the deep quadriceps is more highly vascularized and oxidative than the superficial quadriceps. Using high-power time-resolved NIRS, we tested the hypothesis that deoxygenation of the deep quadriceps would be less than in superficial muscle during incremental cycling exercise in eight males. Pulmonary V̇O2 was measured and muscle deoxyHb + Mb was determined in the superficial vastus lateralis (VL), vastus medialis (VM), and rectus femoris (RF-s) and the deep rectus femoris (RF-d). deoxyHb + Mb in RF-d was significantly less than VL at 70% (67.2 ± 7.0 vs. 75.5 ± 10.7 μM) and 80% (71.4 ± 11.0 vs. 79.0 ± 15.4 μM) of peak work rate (WR(peak)), but greater than VL and VM at WR(peak) (87.7 ± 32.5 vs. 76.6 ± 17.5 and 75.1 ± 19.9 μM). RF-s was intermediate at WR(peak) (82.6 ± 18.7 μM). Total hemoglobin and myoglobin concentration and tissue oxygen saturation were significantly greater in RF-d than RF-s throughout exercise. The slope of deoxyHb + Mb increase (proportional to Q̇O2/V̇O2) in VL and VM slowed markedly above 70% WR(peak), whereas it became greater in RF-d. This divergent deoxygenation pattern may be due to a greater population of slow-twitch muscle fibers in the RF-d muscle and the differential recruitment profiles and vascular and metabolic control properties of specific fiber populations within superficial and deeper muscle regions.
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