Slowed muscle oxygen uptake kinetics with raised metabolism are not dependent on blood flow or recruitment dynamics

Abstract

Key pointsr A slow adjustment of skeletal muscle oxygen uptake (V O 2 ) to produce energy during exercise predisposes to early fatigue.r In human studies,V O 2 kinetics are slow when exercise is initiated from an elevated baseline; this is proposed to reflect slow blood flow regulation and/or recruitment of muscle fibres containing few mitochondria.r To investigate this, we measuredV O 2 kinetics in canine muscle, with experimental control over muscle activation and blood flow.r We found thatV O 2 kinetics remained slow when contractions were initiated from an elevated baseline despite experimentally increased blood flow and uniform fibre activation.r These data challenge our current understanding of the control of muscleV O 2 and demand consideration of new alternative mediators forV O 2 control.Abstract Oxygen uptake kinetics (τV O 2 ) are slowed when exercise is initiated from a raised metabolic rate. Whether this reflects the recruitment of muscle fibres differing in oxidative capacity, or slowed blood flow (Q ) kinetics is unclear. This study determined τV O 2 in canine muscle in situ, with experimental control over muscle activation andQ during contractions initiated from rest and a raised metabolic rate. The gastrocnemius complex of nine anaesthetised, ventilated dogs was isolated and attached to a force transducer. Isometric tetanic contractions (50 Hz; 200 ms duration) via supramaximal sciatic nerve stimulation were used to manipulate metabolic rate: 3 min stimulation at 0.33 Hz (S1), followed by 3 min at 0.67 Hz (S2). Circulation was initially intact (SPON), and subsequently isolated for pump-perfusion (PUMP) above the greatest value in SPON. MuscleV O 2 was determined contraction-by-contraction using an ultrasonic flowmeter and venous oximeter, and normalised to tension-time integral (TTI). τV O 2 /TTI and τQ were less in S1 SPON (mean ± S.D.: 13 ± 3 s and 12 ± 4 s, respectively) than in S2 SPON (29 ± 19 s and 31 ± 13 s, respectively; P < 0.05). τV O 2 /TTI was unchanged by pump-perfusion (S1 PUMP , 12 ± 4 s; S2 PUMP , 24 ± 6 s; P < 0.001) despite increased O 2 delivery; at S2 onset, venous O 2 saturation was 21 ± 4% and 65 ± 5% in SPON and PUMP, respectively.V O 2 kinetics remained slowed when contractions were initiated from a raised metabolic rate despite uniform muscle stimulation and increased O 2 delivery. The intracellular mechanism may relate to a falling energy state, approaching saturating ADP concentration, and/or slowed mitochondrial activation; but further study is required. These data add to the evidence that muscleV O 2 control is more complex than previously suggested.

Pulmonary O2 uptake kinetics during moderate-intensity exercise transitions initiated from low versus elevated metabolic rates: insights from manipulations in cadence

“…However, the dynamics of the NIRS-derived [HHb] signal was shown to adjust (τ[HHb]) at a slower rate (simultaneous with the dynamic adjustments of V O 2p ) in the US compared to the LS in healthy young (MacPhee et al 2005;Williams et al 2013) and older men (Spencer et al 2011) suggesting that the greater τV O 2p was not related to local O 2 availability. This notion was supported by Wust et al (2014), who demonstrated in the electrically stimulated dog gastrocnemius muscle model that the adjustment of muscle O 2 uptake was slower during transitions to a higher vs. lower stimulation rate despite the pre-transition muscle blood flow and O 2 delivery being increased (via pump-perfusion) to the highest level achieved during a spontaneous control condition. Thus, our data and analysis suggest that blood flow and O 2 delivery to and within the microvasculature are unlikely responsible for slower V O 2p kinetics in the US and, in fact, the balance between microvascular O 2 delivery and utilization appeared to more closely match in US compared to LS.…”

The influence of metabolic and circulatory heterogeneity on the expression of pulmonary oxygen uptake kinetics in humans

“…; Wüst et al . ). It is not currently possible to know whether the muscle motor units recruited to transition to low work rates are the same or different from those recruited to transition to greater work rates.…”

“…(), using a model of incomplete muscle recovery, and by Wüst et al . () with exercise transitions in electrically stimulated dog hindlimb muscle. However, DiMenna et al .…”

“…; Wüst et al . ), we simultaneously measured regional muscle deoxygenation by near‐infrared spectroscopy {which includes contributions from both haemoglobin (Hb) and myoglobin (Mb); hereafter referred to as ‘[HHb]’}, which reflects the relationship between microvascular O 2 delivery and O 2 utilization (Murias et al . ).…”

Relationship between (non)linear phase II pulmonary oxygen uptake kinetics with skeletal muscle oxygenation and age in 11–15 year olds

“…Therefore, in the present study, we stress that precedence be given to interpreting the TD and τ of muscle deoxygenation with these preliminary kinetic data supported by the Δdeoxy[Hb+Mb]/Δ ratio to infer the dynamic (mis)matching between O 2 delivery and utilization. Finally, it should be noted that baseline pedalling during M → VH involved simultaneously raising pre‐transition with work rate, which, when both are dissociated, has the potential to influence the and G p via independent mechanisms (Bowen et al., ; DiMenna et al., ; Wust et al., ). Therefore, in the present study, whether an increased baseline work rate per se altered phase II kinetics cannot be established.…”