Hindlimb Oxygen Consumption Research Articles

Evaluation of the Arteriovenous Difference Technique to Simultaneously Estimate Protein Synthesis and Degradation in the Hindlimb of Fed and Chronically Underfed Steers

Our objectives were to validate a technique to measure protein turnover based on net fluxes of tyrosine radioactivity and mass across the hindlimb, and to describe the impact of nutrition on hindlimb protein kinetics and nutrient utilization in growing Holstein steers. External iliac vessels were catheterized to allow for measurements of hindlimb arteriovenous (AV) differences and blood flow. Animals were used in a single reversal design with 16-d periods. Treatments were either 60% (0.6M) or 220% (2.2M) of the energy required for maintenance. On d 12 and 14 of each period, a primed-continuous infusion of L-[side chain-2,3-3H]tyrosine was initiated, followed by a 4-h sampling period to assess hindlimb nutrient utilization and protein kinetics. Well-fed steers exhibited rates of hindlimb utilization for non-nitrogenous energy substrates and amino acids that were consistent with values previously reported for well-fed ruminants. Underfeeding decreased hindlimb blood flow (62%), oxygen consumption (51%) and utilization of respiratory fuels (64-73%). Protein synthesis was also reduced (49%), leading to net nitrogen loss from the hindlimb. The estimated energy cost of protein synthesis accounted for 13% of hindlimb oxygen consumption across intake levels. Hindlimb protein balance was consistent with whole-body balance, adding credence to derived rates of degradation. Overall, data support the validity of the AV difference technique to estimate components of hindlimb protein turnover.

Lower oxygen consumption and Complex I activity in mitochondria isolated from skeletal muscle of fetal sheep with intrauterine growth restriction.

Fetal sheep with placental insufficiency-induced intrauterine growth restriction (IUGR) have lower hindlimb oxygen consumption rates (OCRs), indicating depressed mitochondrial oxidative phosphorylation capacity in their skeletal muscle. We hypothesized that OCRs are lower in skeletal muscle mitochondria from IUGR fetuses, due to reduced electron transport chain (ETC) activity and lower abundances of tricarboxylic acid (TCA) cycle enzymes. IUGR sheep fetuses (n = 12) were created with mid-gestation maternal hyperthermia and compared with control fetuses (n = 12). At 132 ± 1 days of gestation, biceps femoris muscles were collected, and the mitochondria were isolated. Mitochondria from IUGR muscle have 47% lower State 3 (Complex I-dependent) OCRs than controls, whereas State 4 (proton leak) OCRs were not different between groups. Furthermore, Complex I, but not Complex II or IV, enzymatic activity was lower in IUGR fetuses compared with controls. Proteomic analysis (n = 6/group) identified 160 differentially expressed proteins between groups, with 107 upregulated and 53 downregulated mitochondria proteins in IUGR fetuses compared with controls. Although no differences were identified in ETC subunit protein abundances, abundances of key TCA cycle enzymes [isocitrate dehydrogenase (NAD+) 3 noncatalytic subunit β (IDH3B), succinate-CoA ligase ADP-forming subunit-β (SUCLA2), and oxoglutarate dehydrogenase (OGDH)] were lower in IUGR mitochondria. IUGR mitochondria had a greater abundance of a hypoxia-inducible protein, NADH dehydrogenase 1α subcomplex 4-like 2, which is known to incorporate into Complex I and lower Complex I-mediated NADH oxidation. Our findings show that mitochondria from IUGR skeletal muscle adapt to hypoxemia and hypoglycemia by lowering Complex I activity and TCA cycle enzyme concentrations, which together, act to lower OCR and NADH production/oxidation in IUGR skeletal muscle.

Skeletal muscle protein accretion rates and hindlimb growth are reduced in late gestation intrauterine growth-restricted fetal sheep.

Adults who were affected by intrauterine growth restriction (IUGR) suffer from reductions in muscle mass, which may contribute to insulin resistance and the development of diabetes. We demonstrate slower hindlimb linear growth and muscle protein synthesis rates that match the reduced hindlimb blood flow and oxygen consumption rates in IUGR fetal sheep. These adaptations resulted in hindlimb blood flow rates in IUGR that were similar to control fetuses on a weight-specific basis. Net hindlimb glucose uptake and lactate output rates were similar between groups, whereas amino acid uptake was significantly lower in IUGR fetal sheep. Among all fetuses, blood O2 saturation and plasma glucose, insulin and insulin-like growth factor-1 were positively associated and norepinephrine was negatively associated with hindlimb weight. These results further our understanding of the metabolic and hormonal adaptations to reduced oxygen and nutrient supply with placental insufficiency that develop to slow hindlimb growth and muscle protein accretion. Reduced skeletal muscle mass in the fetus with intrauterine growth restriction (IUGR) persists into adulthood and may contribute to increased metabolic disease risk. To determine how placental insufficiency with reduced oxygen and nutrient supply to the fetus affects hindlimb blood flow, substrate uptake and protein accretion rates in skeletal muscle, late gestation control (CON) (n=8) and IUGR (n=13) fetal sheep were catheterized with aortic and femoral catheters and a flow transducer around the external iliac artery. Muscle protein kinetic rates were measured using isotopic tracers. Hindlimb weight, linear growth rate, muscle protein accretion rate and fractional synthetic rate were lower in IUGR compared to CON (P<0.05). Absolute hindlimb blood flow was reduced in IUGR (IUGR: 32.9±5.6mlmin-1 ; CON: 60.9±6.5mlmin-1 ; P<0.005), although flow normalized to hindlimb weight was similar between groups. Hindlimb oxygen consumption rate was lower in IUGR (IUGR: 10.4±1.4μmolmin-1 100g-1 ; CON: 14.7±1.3μmolmin-1 100g-1 ; P<0.05). Hindlimb glucose uptake and lactate output rates were similar between groups, whereas amino acid uptake was lower in IUGR (IUGR: 1.3±0.5μmolmin-1 100g-1 ; CON: 2.9±0.2μmolmin-1 100g-1 ; P<0.05). Blood O2 saturation (r2 =0.80, P<0.0001) and plasma glucose (r2 =0.68, P<0.0001), insulin (r2 =0.40, P<0.005) and insulin-like growth factor (IGF)-1 (r2 =0.80, P<0.0001) were positively associated and norepinephrine (r2 =0.59, P<0.0001) was negatively associated with hindlimb weight. Slower hindlimb linear growth and muscle protein synthesis rates match reduced hindlimb blood flow and oxygen consumption rates in the IUGR fetus. Metabolic adaptations to slow hindlimb growth are probably hormonally-mediated by mechanisms that include increased fetal norepinephrine and reduced IGF-1 and insulin.

Dietary fish oil reduces skeletal muscle oxygen consumption, provides fatigue resistance and improves contractile recovery in the rat in vivo hindlimb

Dietary fish oil modulates skeletal muscle membrane fatty acid composition. Similar changes in heart membrane composition modulate myocardial oxygen consumption and enhance mechanical performance. The rat in vivo autologous perfused hindlimb was used to investigate the influence of membrane composition on skeletal muscle function. Male Wistar rats were fed either saturated fat (SF), n-6 PUFA (linoleic acid rich) or n-3 PUFA (fish oil) diets for 8 weeks. Hindlimb skeletal muscle perfused using the animal's own blood was stimulated via the sciatic nerve (1 Hz, 6-12 V, 0·05 ms) to contract in repeated 10 min bouts. The n-3 PUFA diet markedly increased 22 : 6n-3 DHA, total n-3 PUFA and decreased the n-6:n-3 PUFA ratio (P < 0·05) in red and white skeletal muscle membranes. There was no difference in initial twitch tension but the n-3 PUFA group maintained greater twitch tension within all contraction bouts and recovered better during rest to produce greater twitch tension throughout the final contraction bout (P < 0·05). Hindlimb oxygen consumption during contraction was significantly lower in the n-3 PUFA group compared with the SF group, producing a significantly higher O₂ efficiency index compared with both SF and n-6 PUFA groups (P < 0·05). Resting oxygen consumption was increased in recovery in the SF group (P < 0·05) but did not change in the n-3 PUFA group. Membrane incorporation of n-3 PUFA DHA following fish oil feeding was associated with increased efficiency of muscle O₂ consumption and promoted resistance to muscle fatigue.

EFFECTS OF ENALAPRILAT ON SYMPATHETIC ACTIVITY AND METABOLISM OF EXERCISING MUSCLES IN RABBIT

1. To investigate the effects of angiotensin-converting enzyme inhibition (ACEI) on exercise performance, the following were measured in eight normal rabbits performing graded treadmill exercise during intravenous vehicle saline or enalaprilat infusion: haemodynamics, noradrenaline (NA) spillover, hindlimb oxygen consumption and lactate release. 2. Blood pressure, heart rate (HR), femoral blood flow (FBF), hindlimb lactate release, hindlimb oxygen consumption and hindlimb NA spillover rate were all significantly increased during exercise and the changes during enalaprilat infusion were similar to control responses. 3. At submaximal exercise (6 m/min), ACEI did not significantly alter the responses of hindlimb lactate release, NA spillover rate or oxygen consumption. At the higher exercise load (12 m/min), ACEI reduced hindlimb NA spillover rate (33.1 +/- 4.2 vs 61.3 +/- 17.1 ng/min) and significantly increased oxygen consumption (241 +/- 53.4 vs 133 +/- 23.3%, P < 0.05). The ratio of hindlimb NA spillover rate to total NA spillover rate was markedly increased during exercise, with similar changes being observed in ACEI and control experiments. 4. This study indicates that acute ACEI has a favourable effect on oxygen utilization in exercising muscle in the normal rabbit. Suppression of local sympathetic activation during exercising stress, as reflected in a reduced NA spillover response, may benefit the microcirculation in exercising muscles.

The effects of thermogenic agents on hindlimb oxygen consumption in the dog: ICI D7114 and noradrenaline.

The thermogenic action of beta-adrenoceptor agonists may be due, in part, to increased metabolism in skeletal muscle. Previous results suggest that vasoconstriction is also necessary, and that the effect can be blocked by vasodilators. Both noradrenaline and the beta-3 agonist, ICI D7114, were studied using two dog hindlimb protocols. During constant perfusion conditions, ICI D7114 caused a significant increase in hindlimb oxygen consumption although it is a vasodilator. Noradrenaline resulted in a smaller rise in oxygen consumption, and produced a marked vasoconstriction. Both noradrenaline and ICI D7114 resulted in decreased oxygen consumption when the blood flow was allowed to vary in response to the drug treatment. The results suggest that changes in tissue oxygen consumption caused by beta-agonists are not related to vasomotion.

Effects of ß-hydroxybutyrate infusion on hind limbmetabolism in fetal sheep

This study investigated the effects of high ketone levels on fetal carcass metabolism. Specifically, we aimed to determine whether beta-hydroxybutyrate was taken up by fetal muscle and whether lactate production by the fetal hind limb contributed to the raised circulating lactate levels seen in high ketone states. Hind limb metabolism was studied in 10 chronically catheterized fetal sheep. Substrate/oxygen quotients were measured before and after 2 hour infusions of beta-hydroxybutyrate and compared with the Wilcoxon signed-rank test. beta-Hydroxybutyrate was taken up by hind limb tissues in large amounts (butyrate/oxygen quotient = 1.02 +/- 0.40). Lactate was produced by the hind limb (lactate/oxygen quotient = -0.96 +/- 0.52) in amounts almost equivalent to glucose uptake (glucose/oxygen quotient = 1.32 +/- 0.29). Hind limb oxygen consumption increased 35% and fetal arterial oxygen content fell 16%. beta-Hydroxybutyrate may be consumed by the fetal carcass in amounts sufficient to entirely substitute for glucose. Glucose may then be released as lactate for metabolism elsewhere. Ketones may be important fetal substrates during maternal starvation.

Fetal Hind Limb Oxygen Consumption and Blood Flow during Acute Graded Hypoxia

Fetal Hind Limb Oxygen Consumption and Blood Flow during Acute Graded Hypoxia

Fetal Hind Limb Oxygen Consumption and Blood Flow during Acute Graded Hypoxia

Hind limb blood flow and O2 uptake, mean blood pressure, and heart rate were measured in six fetal sheep at 127-141 d gestation in the control state and at different levels of hypoxia that were induced by partial occlusion of the maternal terminal aorta. Blood flow was measured by an ultrasonic flow transducer. Control fetal arterial O2 content ([O2]a) in the descending aorta was 3.25 + 0.17 mM. In response to graded acute hypoxia, blood flow first increased (22.2 versus 19.9 mL.min-1.100 g-1, p = 0.003) and then decreased abruptly at approximately 1.5 mM [O2]a.O2 uptake decreased about 12% (14.74 versus 16.71, p = 0.03) as [O2]a decreased to 1.5 mM, and then fell markedly, tending toward zero for [O2]a = 0.9 mM. In the 2.7- to 1.5-mM [O2]a range, heart rate increased above control (194 versus 169 min-1, p = 0.0024), whereas mean blood pressure did not change significantly. For [O2]a less than 1.5 mM, heart rate decreased to 148 min-1 (p = 0.0005) and mean blood pressure increased above baseline (55 versus 47 torr, p = 0.0001). In conjunction with previous evidence, these results define a state of acute moderate hypoxia in which the whole fetus can sustain a relatively high rate of oxidative metabolism, and a state of acute severe hypoxia ([O2]a between 1.5 and 1.0 mM) in which O2 uptake by some fetal organs is selectively and markedly decreased.

Regional Circulatory Responses to Hindlimb Work in Developing Swine

Circulatory effects of hindlimb work were studied in 29 swine (aged 1 day to 1 month) anesthetized with pentobarbital. Femoral, renal and intestinal blood flow, resistance and autoregulatory capability were determined at different levels of hindlimb oxygen consumption before and during distal sciatic nerve stimulation. Increases in oxygen consumption were accompanied by hyperemia at all ages, but by increased oxygen extraction only in 2-week and 1-month-old animals, without evidence of autoregulation. Blood flow was consistently redistributed from the kidney and small intestine only in neonates. Older animals generally sustained autoregulation of renal and intestinal blood flows throughout experiments. We concluded that hindlimb work evokes age-related adjustments in regional blood flow that reflect the balance of neural and autoregulatory control.

Factors determining total body and hind limb oxygen consumption in normal and shocked dogs.

O2 uptake is determined by the relative contributions of O2 transport (=blood flow × art.O2 content) and O2 extraction. At constant metabolic rate variations in O2 transport produce inverse changes in O2 extraction (Fig.1),and with changes in metabolic rate the resulting variations in O2 extraction produce a feedback response of the autoregulatory flow system (1). In addition to cellular metabolism, O2 extraction is also determined by the contractile state of the precapillary sphincters (2): the inverse variations in O2 extraction with changes in blood pressure (3) ana arterial pCO2 (4) (Fig.1) are presumably related to this function. In order to quantify these complex interactions we submitted these parameters to multiple regression analysis with O2 uptake as the dependent variable.

Intracellular PO2: a limiting factor in cell respiration.

ARTICLESIntracellular PO2: a limiting factor in cell respirationWJ WhalenWJ WhalenPublished Online:01 Sep 1966https://doi.org/10.1152/ajplegacy.1966.211.3.862MoreSectionsPDF (1 MB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat Previous Back to Top Download PDF FiguresReferencesRelatedInformation Cited ByTissue oxygenation and capacity to deliver O2 do the two go together?Transfusion and Apheresis Science, Vol. 31, No. 1Individual Value of Brain Tissue Oxygen Pressure, Microvascular Oxygen Saturation, Cytochrome Redox Level, and Energy Metabolites in Detecting Critically Reduced Cerebral Energy State During Acute Changes in Global Cerebral PerfusionJournal of Neurosurgical Anesthesiology, Vol. 16, No. 3Skeletal muscle $$\dot V_{O_2 }$$ in rat and lemming: Effect of blood flow rateJournal of comparative physiology, Vol. 128, No. 2Factors Determining Total Body and Hind Limb Oxygen Consumption in Normal and Shocked DogsSauerstoffdruck, Sauerstoffverbrauch und Durchblutung in der Extremit�tenmuskulatur des wachen FroschesPfl�gers Archiv European Journal of Physiology, Vol. 321, No. 1Respiratory problems in pregnancyAmerican Journal of Obstetrics and Gynecology, Vol. 99, No. 7Intracellular Po 2 and Its Regulation in Resting Skeletal Muscle of the Guinea PigCirculation Research, Vol. 21, No. 3Glycogen and phosphocreatine synthesis in the isolated frog sartorius muscleLife Sciences, Vol. 6, No. 4 More from this issue > Volume 211Issue 3September 1966Pages 862-868 Copyright & PermissionsCopyright © 1966 by American Physiological Societyhttps://doi.org/10.1152/ajplegacy.1966.211.3.862PubMed5927916History Published online 1 September 1966 Published in print 1 September 1966 Metrics