Key pointsr The concept of symmorphosis predicts that the capacity of each step of the oxygen cascade is attuned to the task demanded of it during aerobic exercise at maximal rates of oxygen consumption (V O 2 max ) such that no single process is limiting or in excess atV O 2 max .r The present study challenges the applicability of this concept to humans by revealing clear, albeit very different, limitations and excesses in oxygen supply and consumption among untrained and endurance-trained humans.r Among untrained individuals,V O 2 max is limited by the capacity of the mitochondria to consume oxygen, despite an excess of oxygen supply, whereas, among trained individuals,V O 2 max is limited by the supply of oxygen to the mitochondria, despite an excess of mitochondrial respiratory capacity. AbstractThe concept of symmorphosis postulates a matching of structural capacity to functional demand within a defined physiological system, regardless of endurance exercise training status. Whether this concept applies to oxygen (O 2 ) supply and demand during maximal skeletal muscle O 2 consumption (V O 2 max ) in humans is unclear. Therefore, in vitro skeletal muscle mitochondrialV O 2 max ( MitoVO 2 max , mitochondrial respiration of fibres biopsied from vastus lateralis) was compared with in vivo skeletal muscleV O 2 max during single leg knee extensor exercise ( KEVO 2 max , direct Fick by femoral arterial and venous blood samples and Doppler ultrasound blood flow measurements) and whole-bodyV O 2 max during cycling ( BodyVO 2 max , indirect calorimetry) in 10 endurance exercise-trained and 10 untrained young males. In untrained subjects, during KE exercise, maximal O 2 supply ( KEQ O 2max ) exceeded (462 ± 37 ml kg −1 min −1 , P < 0.05) and KEVO 2 max matched (340 ± 22 ml kg −1 min −1 , P > 0.05) MitoVO 2 max (364 ± 16 ml kg −1 min −1 ). Conversely, in trained subjects, both KEQ O 2max (557 ± 35 ml kg −1 min −1 ) and KEVO 2 max (458 ± 24 ml kg −1 min −1 ) fell far short of MitoVO 2 max (743 ± 35 ml kg −1 min −1 , P < 0.05). Although MitoVO 2 max was related to KEVO 2 max (r = 0.69, P < 0.05) and BodyVO 2 max (r = 0.91, P < 0.05) in untrained subjects, these variables were entirely unrelated in trained subjects. Therefore, in untrained subjects,V O 2 max is limited by mitochondrial O 2 demand, with evidence of adequate O 2 supply, whereas, in trained subjects, an exercise training-induced mitochondrial reserve results in skeletal muscleV untrained and trained humans and challenge the concept of symmorphosis as it applies to O 2 supply and demand in humans. Abbreviations BIOPS, biopsy preservation fluid; Body, whole-body; KE, knee extensor; Mito, mitochondrial;Q O 2max , maximum specific oxygen uptake rate;V O2max , maximal oxygen uptake; WR max , maximum work rate.

Objective While vascular dysfunction is well-defined in HF patients with reduced ejection fraction (HFrEF), disease-related alterations in the peripheral vasculature of HF patients with preserved ejection fraction (HFpEF) are not well characterized. Thus, we sought test the hypothesis that HFpEF patients would demonstrate reduced vascular function, at both the conduit artery and microvascular levels, compared to controls. Methods We examined both conduit artery function via brachial artery flow-mediated dilation (FMD) and microvascular function via reactive hyperemia (RH) following 5 min of ischemia in 24 Class II–IV HFpEF patients and 24 healthy controls matched for age, sex, and brachial artery diameter. Results FMD was reduced in HFpEF patients compared to controls (HFpEF: 3.1 ± 0.7%; Controls: 5.1 ± 0.5%; P = 0.03). However, shear rate at time of peak brachial artery dilation was lower in HFpEF patients compared to controls (HFpEF: 42,070 ± 4,018 s−1; Controls: 69,018 ± 9,509 s−1; P = 0.01), and when brachial artery FMD was normalized for the shear stimulus, cumulative area-under-the-curve (AUC) at peak dilation, the between-group differences were eliminated (HFpEF: 0.11 ± 0.03 %/AUC; Controls: 0.09 ± 0.01 %/AUC; P = 0.58). RH, assessed as AUC, was lower in HFpEF patients (HFpEF: 454 ± 35 mL; Controls: 660 ± 63 mL; P < 0.01). Conclusions Collectively, these data suggest that maladaptations at the microvascular level contribute to the pathophysiology of HFpEF, while conduit artery vascular function is not diminished beyond that which occurs with healthy aging.

In patients experiencing migraine without aura, CBF and CBV are reduced during the headache phase. Cerebral oxygen metabolism and oxygen extraction are not significantly affected.

Broxterman RM, Trinity JD, Gifford JR, Kwon OS, Kithas AC, Hydren JR, Nelson AD, Morgan DE, Jessop JE, Bledsoe AD, Richardson RS. Single passive leg movement assessment of vascular function: contribution of nitric oxide. J Appl Physiol 123: 1468-1476, 2017. First published August 31, 2017; doi:10.1152/japplphysiol.00533.2017.-The assessment of passive leg movement (PLM)-induced leg blood flow (LBF) and vascular conductance (LVC) is a novel approach to assess vascular function that has recently been simplified to only a single PLM (sPLM), thereby increasing the clinical utility of this technique. As the physiological mechanisms mediating the robust increase in LBF and LVC with sPLM are unknown, we tested the hypothesis that nitric oxide (NO) is a major contributor to the sPLM-induced LBF and LVC response. In nine healthy men, sPLM was performed with and without NO synthase inhibition by intra-arterial infusion of N-monomethyl-l-arginine (l-NMMA). Doppler ultrasound and femoral arterial pressure were used to determine LBF and LVC, which were characterized by the peak change (ΔLBF and ΔLVC) and area under the curve (LBF and LVC). l-NMMA significantly attenuated ΔLBF [492 ± 153 (l-NMMA) vs. 719 ± 238 (control) ml/min], LBF [57 ± 34 (l NMMA) vs. 147 ± 63 (control) ml], ΔLVC [4.7 ± 1.1 (l-NMMA) vs. 8.0 ± 3.0 (control) ml·min·mmHg], and LVC [0.5 ± 0.3 (l-NMMA) vs. 1.6 ± 0.9 (control) ml/mmHg]. The magnitude of the NO contribution to LBF and LVC was significantly correlated with the magnitude of the control responses ( r = 0.94 for ΔLBF, r = 0.85 for LBF, r = 0.94 for ΔLVC, and r = 0.95 for LVC). These data establish that the sPLM-induced hyperemic and vasodilatory response is predominantly (~65%) NO-mediated. As such, sPLM appears to be a promising, simple, in vivo assessment of NO-mediated vascular function and NO bioavailability. NEW & NOTEWORTHY Passive leg movement (PLM), a novel assessment of vascular function, has been simplified to a single PLM (sPLM), thereby increasing the clinical utility of this technique. However, the role of nitric oxide (NO) in mediating the robust sPLM hemodynamic responses is unknown. This study revealed that sPLM induces a hyperemic and vasodilatory response that is predominantly NO-mediated and, as such, appears to be a promising simple, in vivo, clinical assessment of NO-mediated vascular function and, therefore, NO bioavailability.