V̇o₂ on-kinetics in isolated canine muscle in situ during slowed convective O₂ delivery

Abstract

Goodwin ML, Hernández A, Lai N, Cabrera ME, Gladden LB. VȮ2 on-kinetics in isolated canine muscle in situ during slowed convective O2 delivery. J Appl Physiol 112: 9 -19, 2012. First published October 6, 2011 doi:10.1152/japplphysiol.01480.2010.-The purpose of this study was to examine O2 uptake (V O2) on-kinetics when the spontaneous blood flow (and therefore O2 delivery) onresponse was slowed by 25 and 50 s. The isolated gastrocnemius muscle complex (GS) in situ was studied in six anesthetized dogs during transitions from rest to a submaximal metabolic rate (Ϸ50 -70% of peak V O2). Four trials were performed: 1) a pretrial in which resting and steady-state blood flows were established, 2) a control trial in which the blood flow on-kinetics mean response time (MRT) was set at 20 s (CT20), 3) an experimental trial in which the blood flow on-kinetics MRT was set at 45 s (EX45), and 4) an experimental trial in which the blood flow on-kinetics MRT was set at 70 s (EX70). Slowing O2 delivery via slowing blood flow on-kinetics resulted in a linear slowing of the V O2 on-kinetics response (R ϭ 0.96). Average MRT values for CT20, EX45, and EX70 V O2 on-kinetics were (means Ϯ SD) 17 Ϯ 2, 23 Ϯ 4, and 26 Ϯ 3 s, respectively (P Ͻ 0.05 among all). During these transitions, slowing blood flow resulted in greater muscle deoxygenation (as indicated by near-infrared spectroscopy), suggesting that lower intracellular PO2 values were reached. In this oxidative muscle, V O2 and O2 delivery were closely matched during the transition period from rest to steady-state contractions. In conjunction with our previous work showing that speeding O2 delivery did not alter V O2 on-kinetics under similar conditions, it appears that spontaneously perfused skeletal muscle operates at the nexus of sufficient and insufficient O2 delivery in the transition from rest to contractions. muscle contractions; exercise; blood flow DESPITE ALMOST 100 yr of investigation into the control of oxidative phosphorylation (OxPhos) at the onset of exercise/muscle contractions, the topic remains much debated. In particular, the role of O 2 delivery on the OxPhos response time has been an area of recent discussion and experimentation (13,35,49). This has garnered interest from both basic and applied scientists, in part because many patients who present with slower O 2 uptake (V O 2 ) on-kinetics also exhibit altered blood flow on-kinetics to the working muscles (37) [e.g., patients with chronic obstructive pulmonary disease, some patients with chronic heart failure (9, 19), patients with chronic respiratory disease, patients with peripheral vascular disease, and diabetics].Previous studies (10,33,43,56) have shown that V O 2 onresponses are slowed by breathing hypoxic gas during transitions to submaximal work rates. In contrast, breathing a hyperoxic gas does not speed the V O 2 on-kinetics response (16,33,41,62).When the same principle (altered O 2 delivery) is examined in studies of blood flow alterations, similar results are obtained. For example, when subjects ...

Slowed oxygen uptake kinetics in hypoxia correlate with the transient peak and reduced spatial distribution of absolute skeletal muscle deoxygenation

“…The mechanism of this delayed response remains unclear, but interventions designed to limit the transport of O 2 generally slow kinetics [e.g. β blockade (Hughson & Smyth, 1983), supine exercise (Hughson et al 1991) or slowed pump perfusion (Goodwin et al 2011)]. This expected response formed an integral part of our experimental design, because it allowed us to assess the subsequent relationship amongst slowed kinetics and absolute [HHb] and its spatial heterogeneity.…”

“…Individuals manifesting slowed phase II pulmonary O 2 uptake () kinetics (τ) demonstrate a large, transient ‘overshoot’ in the deoxygenation response at the onset of exercise (Bauer et al 2007; Sperandio et al 2009, 2012; Porcelli et al 2010; Barbosa et al 2011; Bowen et al 2012); a feature that is attenuated or absent in individuals with more rapid kinetics (DeLorey et al 2003; Grassi et al 2003; Sperandio et al 2009; Porcelli et al 2010). Where kinetics are experimentally slowed in the isolated canine hindlimb, the HHb overshoot is increased and kinetics are slowed (Goodwin et al 2011). In addition, the intervention of warm‐up exercise (Bowen et al 2012) and the administration of sildenafil (Sperandio et al 2012) acutely speeded kinetics in chronic heart failure (CHF) patients, and this was associated with a reduction in the HHb overshoot, thus suggesting that a faster adjustment of microvascular O 2 delivery relative to demand may relieve an O 2 delivery limitation to in these patients.…”

“…Importantly, all of the previous studies investigating these dynamic relationships (Sperandio et al 2009, 2012; Goodwin et al 2011; Bowen et al 2012) were unable to quantify the absolute concentration of the deoxygenation ([HHb]) overshoot. Continuous‐wave NIRS (CW‐NIRS) makes only relative, normalized, measures of haem chromophore concentrations.…”

Validation of a high-power, time-resolved, near-infrared spectroscopy system for measurement of superficial and deep muscle deoxygenation during exercise

“…This response has been explained on the basis of deep muscle containing proportionally more slowtwitch (type I) muscle fibers with a greater sensitivity of vasodilatory control (2,28). Goodwin et al (14) used NIRS directly on the surface of canine hindlimb muscles to access both superficial and deep muscle deoxygenation during stimulated contractions. They showed that slowed blood flow speeded the rate of muscle deoxygenation during the transition from rest to steady state.…”

Simultaneous sampling of tissue oxygenation and oxygen consumption in skeletal muscle

“…The partial pressure of O 2 in the interstitial space (P ISF O 2 ), which is dissociated from red blood cell (RBC) hemoglobin and free to diffuse to intracellular mitochondrial sinks without appreciable interference from myoglobin desaturation, is sensitive to rapid changes in the balance between supply and demand. Different approaches ranging from whole animals (Hoyt, Wickler et al 2006, Rodrigues, Figueroa et al 2007), isolated muscles (Goodwin, Hernandez et al 2012); (McDonough, Behnke et al 2005), to single fibers (Hogan 2001); (Kindig, Howlett et al 2003); (Wust, van der Laarse et al 2013) have sought to characterize the relationship of the partial pressure of O 2 (PO 2 ) and VO 2 . The description of P ISF O 2 supply/demand coupling for intact muscle preparations in vivo , however, remains incomplete.…”