Lled 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) 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....

The maximum rate of O₂ uptake (i.e., V̇o_2max), as measured during large muscle mass exercise such as cycling or running, is widely considered to be the gold standard measurement of integrated cardiopulmonary-muscle oxidative function. The development of rapid-response gas analyzers, enabling measurement of breath-by-breath pulmonary gas exchange, has facilitated replacement of the discontinuous progressive maximal exercise test (that produced an unambiguous V̇o₂-work rate plateau definitive for V̇o_2max) with the rapidly incremented or ramp testing protocol. Although this is more suitable for clinical and experimental investigations and enables measurement of the gas exchange threshold, exercise efficiency, and V̇o₂ kinetics, a V̇o₂-work rate plateau is not an obligatory outcome. This shortcoming has led to investigators resorting to so-called secondary criteria such as respiratory exchange ratio, maximal heart rate, and/or maximal blood lactate concentration, the acceptable values of which may be selected arbitrarily and result in grossly inaccurate V̇o_2max estimation. Whereas this may not be an overriding concern in young, healthy subjects with experience of performing exercise to volitional exhaustion, exercise test naïve subjects, patient populations, and less motivated subjects may stop exercising before their V̇o_2max is reached. When V̇o_2max is a or the criterion outcome of the investigation, this represents a major experimental design issue. This CORP presents the rationale for incorporation of a second, constant work rate test performed at ~110% of the work rate achieved on the initial ramp test to resolve the classic V̇o₂-work rate plateau that is the unambiguous validation of V̇o_2max. The broad utility of this procedure has been established for children, adults of varying fitness, obese individuals, and patient populations.

Key points: Inorganic nitrate (NO₃⁻) supplementation with beetroot juice (BR) in humans lowers blood pressure and the O₂ cost of exercise and may improve exercise tolerance following its reduction to nitrite (NO₂⁻) and nitric oxide (NO). The effect of inorganic NO₃⁻ supplementation with BR on skeletal muscle blood flow (BF) and vascular conductance (VC) within and among locomotory muscles during exercise is unknown. Inorganic NO₃⁻ supplementation with BR in rats resulted in lower exercising mean arterial pressure, lower blood [lactate], and higher total skeletal muscle hindlimb BF and VC during submaximal treadmill running. The greater BF and VC was found in muscles and muscle parts containing primarily type IIb + d/x muscle fibres. These data demonstrate that inorganic NO₃⁻ supplementation improves vascular control and elevates skeletal muscle O₂ delivery during exercise predominantly in fast‐twitch type II muscles, and provide a potential mechanism by which NO₃⁻ supplementation improves metabolic control. Abstract  Dietary nitrate (NO₃⁻) supplementation, via its reduction to nitrite (NO₂⁻) and subsequent conversion to nitric oxide (NO) and other reactive nitrogen intermediates, reduces blood pressure and the O₂ cost of submaximal exercise in humans. Despite these observations, the effects of dietary NO₃⁻ supplementation on skeletal muscle vascular control during locomotory exercise remain unknown. We tested the hypotheses that dietary NO₃⁻ supplementation via beetroot juice (BR) would reduce mean arterial pressure (MAP) and increase hindlimb muscle blood flow in the exercising rat. Male Sprague–Dawley rats (3–6 months) were administered either NO₃⁻ (via beetroot juice; 1 mmol kg⁻¹ day⁻¹, BR n= 8) or untreated (control, n= 11) tap water for 5 days. MAP and hindlimb skeletal muscle blood flow and vascular conductance (radiolabelled microsphere infusions) were measured during submaximal treadmill running (20 m min⁻¹, 5% grade). BR resulted in significantly lower exercising MAP (control: 137 ± 3, BR: 127 ± 4 mmHg, P < 0.05) and blood [lactate] (control: 2.6 ± 0.3, BR: 1.9 ± 0.2 mm, P < 0.05) compared to control. Total exercising hindlimb skeletal muscle blood flow (control: 108 ± 8, BR: 150 ± 11 ml min⁻¹ (100 g)⁻¹, P < 0.05) and vascular conductance (control: 0.78 ± 0.05, BR: 1.16 ± 0.10 ml min⁻¹ (100 g)⁻¹ mmHg⁻¹, P < 0.05) were greater in rats that received BR compared to control. The relative differences in blood flow and vascular conductance for the 28 individual hindlimb muscles and muscle parts correlated positively with their percentage type IIb + d/x muscle fibres (blood flow: r= 0.74, vascular conductance: r= 0.71, P < 0.01 for both). These data support the hypothesis that NO₃⁻ supplementation improves vascular control and elevates skeletal muscle O₂ delivery during exercise predominantly in fast‐twitch type II muscles, and provide a potential mechanism by which NO₃⁻ supplementation improves metabolic control.

The defining characteristic of chronic heart failure (CHF) is an exercise intolerance that is inextricably linked to structural and functional aberrations in the O₂ transport pathway. CHF reduces muscle O₂ supply while simultaneously increasing O₂ demands. CHF severity varies from moderate to severe and is assessed commonly in terms of the maximum O₂ uptake, which relates closely to patient morbidity and mortality in CHF and forms the basis for Weber and colleagues' ( 167 ) classifications of heart failure, speed of the O₂ uptake kinetics following exercise onset and during recovery, and the capacity to perform submaximal exercise. As the heart fails, cardiovascular regulation shifts from controlling cardiac output as a means for supplying the oxidative energetic needs of exercising skeletal muscle and other organs to preventing catastrophic swings in blood pressure. This shift is mediated by a complex array of events that include altered reflex and humoral control of the circulation, required to prevent the skeletal muscle “sleeping giant” from outstripping the pathologically limited cardiac output and secondarily impacts lung (and respiratory muscle), vascular, and locomotory muscle function. Recently, interest has also focused on the dysregulation of inflammatory mediators including tumor necrosis factor-α and interleukin-1β as well as reactive oxygen species as mediators of systemic and muscle dysfunction. This brief review focuses on skeletal muscle to address the mechanistic bases for the reduced maximum O₂ uptake, slowed O₂ uptake kinetics, and exercise intolerance in CHF. Experimental evidence in humans and animal models of CHF unveils the microvascular cause(s) and consequences of the O₂ supply (decreased)/O₂ demand (increased) imbalance emblematic of CHF. Therapeutic strategies to improve muscle microvascular and oxidative function (e.g., exercise training and anti-inflammatory, antioxidant strategies, in particular) and hence patient exercise tolerance and quality of life are presented within their appropriate context of the O₂ transport pathway.