Critical P O 2 of skeletal muscle in vivo

1999 ◽  
Vol 277 (5) ◽  
pp. H1831-H1840 ◽  
Author(s):  
Keith N. Richmond ◽  
Ross D. Shonat ◽  
Ronald M. Lynch ◽  
Paul C. Johnson

The main purpose of this study was to determine the interstitial oxygen tension at which aerobic metabolism becomes limited (critical [Formula: see text]) in vivo in resting skeletal muscle. Using an intravital microscope system, we determined the interstitial oxygen tension at 20-μm-diameter tissue sites in rat spinotrapezius muscle from the phosphorescence lifetime decay of a metalloporphyrin probe during a 1-min stoppage of muscle blood flow. In paired experiments NADH fluorescence was measured at the same sites during flow stoppage. NADH fluorescence rose significantly above control when interstitial[Formula: see text] fell to 2.9 ± 0.5 mmHg ( n = 13) and was not significantly different (2.4 ± 0.5 mmHg) when the two variables were first averaged for all sites and then compared. Similar values were obtained using the abrupt change in rate of[Formula: see text] decline as the criterion for critical [Formula: see text]. With a similar protocol, we determined that NADH rose significantly at a tissue site centered 30 μm from a collecting venule when intravascular[Formula: see text] fell to 7.2 ± 1.5 mmHg. The values for critical interstitial and critical intravascular[Formula: see text] are well below those reported during free blood flow in this and in other muscle preparations, suggesting that oxygen delivery is regulated at levels well above the minimum required for oxidative metabolism. The extracellular critical[Formula: see text] found in this study is slightly greater than previously found in vitro, possibly due to differing local conditions rather than a difference in metabolic set point for the mitochondria.

2008 ◽  
Vol 116 (2) ◽  
pp. 157-164 ◽  
Author(s):  
Marlies Bosselaar ◽  
Paul Smits ◽  
Cees J. Tack

Ischaemia, like muscle contraction, has been reported to induce skeletal muscle glucose uptake in in vitro models. This stimulating effect appears independent of insulin and is probably mediated by activation of AMPK (AMP-activated protein kinase). In the present study, we hypothesized that in vivo in humans ischaemia- and insulin-induced glucose uptake are additive, and that the combined impact of ischaemia and contraction on glucose uptake is of a similar magnitude when each is applied separately. We assessed the effects of ischaemia with and without euglycaemic–hyperinsulinaemia (clamp; protocol 1) and with and without muscle contraction (protocol 2) on muscle FGU (forearm glucose uptake) in healthy subjects. Furthermore, we assessed the impact of ischaemia on FBF (forearm blood flow; plethysmography). In protocol 1, ischaemia increased FGU from 0.6±0.1 at baseline to 5.5±1.9 μmol·min−1·dl−1, and insulin increased FGU to 1.6±0.3 μmol·min−1·dl−1 (P<0.05 for both). The combination of ischaemia+insulin increased FGU to 15.5±2.2 μmol·min−1·dl−1 (P<0.05 compared with each stimulus alone). Maximal FBF obtained after ischaemia was similar with and without hyperinsulinaemia. In protocol 2, isometric contraction increased FGU from 0.3±0.1 to 2.7±0.8 μmol·min−1·dl−1 (P<0.05), but FGU was not significantly different from ischaemia compared with ischaemia+contraction. However, combined ischaemia+contraction resulted in a greater increase in FBF. In summary, ischaemia and insulin independently stimulate skeletal muscle glucose uptake in vivo in humans, whereas ischaemia and contraction do not. The observed differential effects of these stimuli on glucose uptake appear to be unrelated to changes in muscle blood flow.


2011 ◽  
Vol 110 (3) ◽  
pp. 695-704 ◽  
Author(s):  
Danielle J. McCullough ◽  
Robert T. Davis ◽  
James M. Dominguez ◽  
John N. Stabley ◽  
Christian S. Bruells ◽  
...  

With advancing age, there is a reduction in exercise tolerance, resulting, in part, from a perturbed ability to match O2 delivery to uptake within skeletal muscle. In the spinotrapezius muscle (which is not recruited during incline treadmill running) of aged rats, we tested the hypotheses that exercise training will 1) improve the matching of O2 delivery to O2 uptake, evidenced through improved microvascular Po2 (PmO2), at rest and throughout the contractions transient; and 2) enhance endothelium-dependent vasodilation in first-order arterioles. Young (Y, ∼6 mo) and aged (O, >24 mo) Fischer 344 rats were assigned to control sedentary (YSED; n = 16, and OSED; n = 15) or exercise-trained (YET; n = 14, and OET; n = 13) groups. Spinotrapezius blood flow (via radiolabeled microspheres) was measured at rest and during exercise. Phosphorescence quenching was used to quantify PmO2 in vivo at rest and across the rest-to-twitch contraction (1 Hz, 5 min) transition in the spinotrapezius muscle. In a follow-up study, vasomotor responses to endothelium-dependent (acetylcholine) and -independent (sodium nitroprusside) stimuli were investigated in vitro. Blood flow to the spinotrapezius did not increase above resting values during exercise in either young or aged groups. Exercise training increased the precontraction baseline PmO2 (OET 37.5 ± 3.9 vs. OSED 24.7 ± 3.6 Torr, P < 0.05); the end-contracting PmO2 and the time-delay before PmO2 fell in the aged group but did not affect these values in the young. Exercise training improved maximal vasodilation in aged rats to acetylcholine (OET 62 ± 16 vs. OSED 27 ± 16%) and to sodium nitroprusside in both young and aged rats. Endurance training of aged rats enhances the PmO2 in a nonrecruited skeletal muscle and is associated with improved vascular smooth muscle function. These data support the notion that improvements in vascular function with exercise training are not isolated to the recruited muscle.


1999 ◽  
Vol 58 (4) ◽  
pp. 919-923 ◽  
Author(s):  
Jan Henriksson

Techniques in human skeletal muscle research are by necessity predominantly 'descriptive'.Microdialysis has raised high expectations that it could meet the demand for a method that allows 'mechanistic' investigations to be performed in human skeletal muscle. In the present review, some views are given on how well the initial expectations on the use of the microdialysis technique in skeletal muscle have been fulfilled, and the areas in which additional work is needed in order to validate microdialysis as an important metabolic technique in this tissue. The microdialysis catheter has been equated to an artificial blood vessel, which is introduced into the tissue. By means of this 'vessel' the concentrations of compounds in the interstitial space can be monitored. The concentration of substances in the collected samples is dependent on the rate of perfusate flow. When perfusate flow is slow enough to allow complete equilibration between interstitial and perfusate fluids, the concentration in the perfusate is maximal and identical to the interstitial concentration. Microdialysis data may be influenced by changes in blood flow, especially in instances where the tissue diffusivity limits the recovery in vivo, i.e. when recovery in vitro is 100 %, whereas the recovery in vivo is less than 100 %. Microdialysis data indicate that a significant arterial-interstitial glucose concentration gradient exists in skeletal muscle but not in adipose tissue at rest. While the concentrations of glucose and lactate in the dialysate from skeletal muscle are close to the expected values, the glycerol values obtained for muscle are still puzzling. Ethanol added to the perfusate will be cleared by the tissue at a rate that is determined by the nutritive blood flow (the microdialysis ethanol technique). It is concluded that microdialysis of skeletal muscle has become an important technique for mechanistic studies in human metabolism and nutrition.


1995 ◽  
Vol 268 (1) ◽  
pp. H330-H335 ◽  
Author(s):  
R. M. McAllister ◽  
J. C. Sansone ◽  
M. H. Laughlin

Hyperthyroidism is associated with exercise intolerance. Previous research, however, has shown that cardiac output is either normal or enhanced during exercise in the hyperthyroid state. We therefore hypothesized that blood flow to working skeletal muscle is augmented in hyperthyroid animals during in vivo submaximal exercise and, consequently, that noncardiovascular factors are responsible for intolerance to exercise. To test this hypothesis, rats were made hyperthyroid (Hyper) over 6–12 wk with injections of triiodothyronine (300 micrograms/kg). Hyperthyroidism was evidenced by left ventricular hypertrophy [euthyroid (Eut), 2.12 +/- 0.05 mg/g body wt; Hyper, 2.78 +/- 0.06; P < 0.005], 25–60% increases in citrate synthase activities in Hyper hindlimb muscles over those of Eut rats, and higher preexercise heart rates (Eut, 415 +/- 18 beats/min; Hyper, 479 +/- 19; P < 0.025). Regional blood flows were determined by the radiolabeled microsphere method, preexercise, and at 1–2 min of treadmill running at 15 m/min (0% grade). Total hindlimb muscle blood flow preexercise was unaffected (Eut, 31 +/- 4 ml.min-1.(100) g-1, n = 11; Hyper, 40 +/- 6, n = 9; not significant) but was higher (P < 0.025) in Hyper (127 +/- 17, n = 9) compared with Eut (72 +/- 11, n = 9) during treadmill running. During exercise, flows to individual muscles and muscle sections were approximately 50–150% higher in Hyper compared with Eut rats. Visceral blood flows were largely similar between groups. These findings indicate that hyperthyroidism is associated with augmented blood flow to skeletal muscle during submaximal exercise. Thus hypoperfusion of skeletal muscle does not account for the poor exercise tolerance characteristic of hyperthyroidism.


2013 ◽  
Vol 114 (8) ◽  
pp. 1085-1093 ◽  
Author(s):  
Anne R. Crecelius ◽  
Brett S. Kirby ◽  
Jennifer C. Richards ◽  
Frank A. Dinenno

Intravascular adenosine triphosphate (ATP) evokes vasodilation and is implicated in the regulation of skeletal muscle blood flow during exercise. Mechanical stresses to erythrocytes and endothelial cells stimulate ATP release in vitro. How mechanical effects of muscle contractions contribute to increased plasma ATP during exercise is largely unexplored. We tested the hypothesis that simulated mechanical effects of muscle contractions increase [ATP]venous and ATP effluent in vivo, independent of changes in tissue metabolic demand, and further increase plasma ATP when superimposed with mild-intensity exercise. In young healthy adults, we measured forearm blood flow (FBF) (Doppler ultrasound) and plasma [ATP]v (luciferin-luciferase assay), then calculated forearm ATP effluent (FBF×[ATP]v) during rhythmic forearm compressions (RFC) via a blood pressure cuff at three graded pressures (50, 100, and 200 mmHg; Protocol 1; n = 10) and during RFC at 100 mmHg, 5% maximal voluntary contraction rhythmic handgrip exercise (RHG), and combined RFC + RHG ( Protocol 2; n = 10). [ATP]v increased from rest with each cuff pressure (range 144–161 vs. 64 ± 13 nmol/l), and ATP effluent was graded with pressure. In Protocol 2, [ATP]v increased in each condition compared with rest (RFC: 123 ± 33; RHG: 51 ± 9; RFC + RHG: 96 ± 23 vs. Mean Rest: 42 ± 4 nmol/l; P < 0.05), and ATP effluent was greatest with RFC + RHG (RFC: 5.3 ± 1.4; RHG: 5.3 ± 1.1; RFC + RHG: 11.6 ± 2.7 vs. Mean Rest: 1.2 ± 0.1 nmol/min; P < 0.05). We conclude that the mechanical effects of muscle contraction can 1) independently elevate intravascular ATP draining quiescent skeletal muscle without changes in local metabolism and 2) further augment intravascular ATP during mild exercise associated with increases in metabolism and local deoxygenation; therefore, it is likely one stimulus for increasing intravascular ATP during exercise in humans.


2002 ◽  
Vol 95 (4) ◽  
pp. 1080-1086
Author(s):  
Greta M. Palmer ◽  
Brian E. Cairns ◽  
Steven L. Berkes ◽  
Patricia S. Dunning ◽  
George A. Taylor ◽  
...  

2000 ◽  
Vol 279 (4) ◽  
pp. H1757-H1766 ◽  
Author(s):  
Rabelais Tatchum-Talom ◽  
Richard Schulz ◽  
J. Robert McNeill ◽  
Fadi H. Khadour

Exercise enhances cardiac output and blood flow to working skeletal muscles but decreases visceral perfusion. The alterations in nitric oxide synthase (NOS) activity and/or expression of the cardiopulmonary, skeletal muscle, and visceral organs induced by swim training are unknown. In sedentary and swim-trained rats (60 min twice/day for 3–4 wk), we studied the alterations in NOS in different tissues along with hindquarter vasoreactivity in vivo during rest and mesenteric vascular bed reactivity in vitro. Hindquarter blood flow and conductance were reduced by norepinephrine in both groups to a similar degree, whereas N G-nitro-l-arginine methyl ester reduced both indexes to a greater extent in swim-trained rats. Vasodilator responses to ACh, but not bradykinin or S-nitroso- N-acetyl-penicillamine, were increased in swim-trained rats. Ca2+-dependent NOS activity was enhanced in the hindquarter skeletal muscle, lung, aorta, and atria of swim-trained rats together with increased expression of neuronal NOS in the hindquarter skeletal muscle and endothelial NOS in the cardiopulmonary organs. Mesenteric arterial bed vasoreactivity was unaltered by swim training. Physiological adaptations to swim training are characterized by enhanced hindquarter ACh-induced vasodilation with upregulation of neuronal NOS in skeletal muscle and endothelial NOS in the lung, atria, and aorta.


2002 ◽  
Vol 95 (4) ◽  
pp. 1080-1086 ◽  
Author(s):  
Greta M. Palmer ◽  
Brian E. Cairns ◽  
Steven L. Berkes ◽  
Patricia S. Dunning ◽  
George A. Taylor ◽  
...  

2019 ◽  
Vol 119 (11) ◽  
pp. 1752-1766 ◽  
Author(s):  
Xiaoqiang Chen ◽  
Weilan Wu ◽  
Shifei Wang ◽  
Jiayuan Zhong ◽  
Nima Moumin Djama ◽  
...  

Background Magnetic targeting may help microbubbles (MBs) reach obstructive thrombi and improve the efficacy of MB-mediated sonothrombolysis, but the role of magnetic targeting in MB-mediated sonothrombolysis remains elusive. Objectives We investigate the feasibility and efficacy of magnetically targeted MB-mediated sonothrombolysis for the treatment of obstructive thrombi. Materials and Methods Red and white thromboembolic models were established in vitro and in vivo. The models were randomly assigned to the control, ultrasound plus control MB (US + C-MB), ultrasound plus magnetic MB (US + M-MB), or US + M-MB + recombinant tissue-type plasminogen activator (r-tPA) groups and treated for 30 minutes. The recanalization rate, average blood flow velocity, hindlimb perfusion, and skeletal muscle injury marker levels were recorded. Results The recanalization rate, average blood flow velocity, and hindlimb perfusion in the red and white thromboembolic models were all significantly higher in the US + M-MB and US + M-MB + r-tPA groups than in the control and US + C-MB groups both in vitro and in vivo. Moreover, the levels of the skeletal muscle injury markers were all significantly lower in the US + M-MB and US + M-MB + r-tPA groups than in the other two groups in vivo for both thromboembolic models. However, the thrombolytic effects of red thrombi performed better than those of white thrombi in the US + M-MB + r-tPA group. Conclusion M-MB-mediated sonothrombolysis improves the efficacy of thrombolysis both in vitro and in vivo, and reduces tissue damage in clogging model; thus, this method may serve as a promising approach for treating thrombus-occlusive diseases.


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