Skeletal Muscle Oxygen Tension Research Articles

Moderate Hypoxia Exposure: A Novel Strategy to Improve Glucose Metabolism in Humans?

The obesity epidemic calls for novel strategies to prevent and treat obesity and its comorbidities. Several studies have indicated that the amount of oxygen to which tissues are exposed may substantially impact cardiometabolic health. Interestingly, living at high altitude (hypobaric hypoxia) seems to be associated with improved glucose homeostasis and a decreased prevalence of Type 2 diabetes. Furthermore, normobaric hypoxia exposure has been shown to exert beneficial effects on glucose homeostasis and insulin sensitivity in rodents and humans. This may, at least in part, be explained by altered adipose tissue and skeletal muscle oxygen tension. In contrast, patients with obstructive sleep apnoea syndrome, which is characterised by episodes of severe intermittent hypoxia due to periodic collapse of the upper airway during sleep, show impairments in glucose homeostasis and are at increased cardiovascular risk. These discrepancies may be explained by the severity, duration, and pattern (number of cycles) of hypoxic episodes, but underlying mechanisms have not yet been studied in detail. The purpose of this review is to provide an overview of available studies on the link between oxygen tension, inflammation, and glucose homeostasis. Detailed studies to elucidate the effects of moderate hypoxia exposure on wholebody and tissue-specific insulin sensitivity in humans are clearly warranted.

The Influence of Allogeneic Red Blood Cell Transfusion Compared with 100% Oxygen Ventilation on Systemic Oxygen Transport and Skeletal Muscle Oxygen Tension After Cardiac Surgery

The Influence of Allogeneic Red Blood Cell Transfusion Compared with 100% Oxygen Ventilation on Systemic Oxygen Transport and Skeletal Muscle Oxygen Tension After Cardiac Surgery

Effects of isovolaemic haemodilution on oxygenation of liver and skeletal muscle

Hydroxyethyl starch is frequently used for volume substitution during surgical procedures and for isovolaemic haemodilution. Haemodilution has also been shown to improve tissue oxygen tension in skeletal muscle: However, effects of this volume substitute on tissue oxygen tension of the liver during haemodilution remains unknown. Fourteen foxhounds were anaesthetized with fentanyl/midazolam and mechanically ventilated with 30% oxygen. Following splenectomy animals were randomly assigned to a control group without haemodilution but fluid substitution with Ringer's lactate (Group C) or underwent isovolaemic haemodilution to a haematocrit of 25% with hydroxyethyl starch 70/0.5 (Group H). Haemodynamic parameters and oxygen transport during 100 min following isovolaemic haemodilution were measured. Liver oxygen tension was recorded using a flexible polarographic electrode tonometer, whereas in the muscle a polarographic needle probe was used. Animal characteristics and baseline haematocrit were similar in both groups. At baseline the tissue oxygen tension of liver and skeletal muscle were not different between groups. Haemodilution with hydroxyethyl starch 70/0.5 provided augmentation of mean liver tissue oxygen tension (baseline: 46 +/- 13 mmHg; 20 min: 60.3 +/- 12 mmHg; 60 min: 60 +/- 16 mmHg; 100 min: 63 +/- 16 mmHg; P < 0.05 vs. baseline), while oxygen tensions in Group C remained unchanged (baseline: 48 +/- 16 mmHg; 20 min: 52 +/- 19 mmHg; 60 min: 49 +/- 12 mmHg; 100 min: 52 +/- 16 mmHg) and no differences could be detected between groups. Oxygen tension in skeletal muscle changed as follows: Group H - baseline: 24 +/- 32 mmHg; 20 min: 32 +/- 3 mmHg; 60 min: 33 +/- 7 mmHg; 100 min: 33 +/- 11 mmHg. Group C - baseline: 22 +/- 6 mmHg; 20 min: 21 +/- 3 mmHg; 60 min: 24 +/- 4 mmHg; 100 min: 18 +/- 4 mmHg (P < 0.05 vs. baseline, p < 0.05 vs. Group C). In this animal model, isovolaemic haemodilution with hydroxyethyl starch 70/0.5 increased tissue oxygen tension in liver and skeletal muscle in comparison with baseline values. However, when compared between groups haemodilution only resulted in an increase of tissue oxygen tension in the muscle but not in the liver.

Adeno-associated viral vector-mediated gene transfer of VEGF normalizes skeletal muscle oxygen tension and induces arteriogenesis in ischemic rat hindlimb.

Critical limb ischemia is an important clinical problem that often leads to disability and limb loss. Vascular endothelial growth factor (VEGF), delivered either as recombinant protein or as gene therapy, has been shown to promote both collateral artery formation (arteriogenesis) and capillary angiogenesis in animal models of hindlimb ischemia. However, none of the previous studies has demonstrated an improvement in tissue hypoxia, the condition that drives the molecular response to ischemia. Furthermore, the optimal vector and route of gene delivery have not been determined. Recently, adeno-associated viral (AAV) vectors, which efficiently transduce skeletal muscle and produce sustained transgene expression, have been used as gene therapy vectors. We asked whether an intra-arterial injection of AAV-VEGF(165) normalizes muscle oxygen tension by increasing skeletal muscle oxygen tension, and promotes arteriogenesis and angiogenesis in a rat model of severe hindlimb ischemia. We found that AAV-VEGF treatment normalized muscle oxygen tension in the ischemic limb. In contrast, vehicle and AAV-lacZ-treated limbs remained ischemic. Collateral arteries were more numerous in AAV-VEGF-treated rats, but, surprisingly, capillaries were not. We conclude that intra-arterial AAV-mediated gene transfer of AAV-VEGF(165) normalizes muscle oxygen tension and leads to arteriogenesis in rats with severe hindlimb ischemia.

Liposome-encapsulated hemoglobin does not exacerbate endotoxin-induced lung injury.

To test the hypothesis that liposome encapsulated hemoglobin (LEH), an experimental oxygen-carrying fluid, exacerbates endotoxin-induced lung injury in the rat. Prospective, randomized animal study. University animal laboratory. Anesthetized Sprague-Dawley rats (n = 8-13) were infused with LEH (10% of estimated total blood volume) or vehicle (0.9% NaCl). Thirty minutes later, Escherichia coli endotoxin (3.6 mg/kg, i.v.) or vehicle (0.9% NaCl) was administered, and skeletal muscle oxygen tension as well as lung injury were assessed at 2, 4, and 8 hrs. Oxygen tension was measured using a miniaturized thin film oxygen sensor placed in the rectus abdominis muscle, and lung injury was evaluated by determining lung weights, lung myeloperoxidase activity, lung tissue tumor necrosis factor-alpha level, and protein concentration in bronchoalveolar lavage fluid. The intravenous bolus injection of E. coli endotoxin elevated lung water content (33% +/- 5%; p < .01 vs. sham controls), myeloperoxidase activity (56% +/- 6%; p < .01), and tumor necrosis factor-alpha production (1320 +/- 154 pg/g lung tissue; p < .05 vs. undetected levels in sham controls), as well as induced protein accumulation in bronchoalveolar lavage fluid (258% +/- 38%; p < .01) and skeletal muscle hypoxia (52 +/- 8 mm Hg; p < .05). Pretreatment with LEH, which when infused alone did not induce lung injury, had no effect on these responses. In this specific model of endotoxin-induced lung injury, LEH does not exacerbate microvascular leakage and leukosequestration, the hallmarks of adult respiratory distress syndrome.

Bovine hemoglobin. HBOC-201 causes a reduction of the oxygen partial pressure in poststenotic skeletal muscle

We investigated the effects of ultrapurified polymerized bovine hemoglobin (HBOC-201) on skeletal muscle tissue oxygen tension when applied before establishment of a nearly complete arterial stenosis. Twelve foxhounds were anaesthetized IV and mechanically ventilated with 30% oxygen in air. Catheters were inserted into the right femoral artery and vein for measurements of haemodynamic parameters and blood-gas sampling. Arterial blood flow of the left popliteal artery was measured by an electromagnetic flow probe. Skeletal muscle tissue oxygen tension (tpo2) was measured in the left gastrocnemic muscle using a stepwise-driven polarographic needle probe, creating histograms from 200 single tpO2 measurements. Following isovolaemic haemodilution with Ringer's solution to a target haematocrit of 20%, the animals were randomly assigned to receive either 200 ml of predonated fresh blood (group 1) or 200 ml of HBOC-201 (MW 32,000-500,000; Hb 13 +/- 1 g-dl-1, group 2). After a 15-min stabilization period, a 95% artificial stenosis of the left popliteal artery was established. While animals of group 1 received two applications of 200 ml 6% hetastarch (HES, 200,000; 0.5), animals of group 2 received 200 ml Ringer's solution 45 and 75 min after establishment of the arterial stenosis, respectively. Variables were measured at baseline, after haemodilution and application of the respective compound, and 30, 60 and 90 min after establishment of the stenosis. Demographic data, muscle temperature and arterial blood gases did not differ between groups. With the exception of a higher mean pulmonary artery pressure in HBOC-201-treated animals, haemodynamics did not differ between groups. In both groups oxygen delivery and oxygen consumption of the muscle decreased in parallel to the decreasing blood flow during arterial stenosis. In contrast, oxygen extraction ratio increased after infusion of HBOC-201 and remained unchanged during stenosis (P < 0.05). In group 1, the tpO2 decreased during stenosis when compared to baseline (P < 0.001) and remained decreased after administration of HES. In contrast, administration of 200 ml of HBOC-201 before establishment of the arterial stenosis sustained the tpO2 values at nearly baseline levels during stenosis. Skeletal muscle tissue oxygen tension was higher after HBOC-201 infusion during stenosis when compared to HES infusion (P < 0.001). These data suggest that haemoglobin solutions can reach poststenotic tissues. The increased oxygen extraction after application of HBOC-201 is associated with improved skeletal muscle oxygen tension during severe arterial stenosis.

Haemodynamic changes and skeletal muscle oxygen tension during complete blood exchange with ultrapurified polymerized bovine haemoglobin.

The study investigates the effect of continuous blood exchange with ultrapurified, polymerized bovine haemoglobin (UPBH) in comparison to hetastarch on haemodynamics, oxygen transport and skeletal muscle oxygen tension in a canine model. Sixteen anaesthetized beagle dogs underwent haemodilution with lactated Ringer's to a starting haematocrit of 20% followed by progressive blood exchange with 6% hetastarch 200,000/0.5 (HES, group 1) or UPBH (haemoglobin 13 +/- 1 g.dl-1, molecular weight (MW) 32-500,000, group 2) to haematocrit target levels of 15%, 10% and 5% or less. Besides haemodynamics, skeletal muscle tissue oxygen tension (tPO2) was measured using a polarographic needle probe. In HES-treated animals, heart rate, cardiac output and blood flow were higher while systemic vascular resistance, systemic and regional arterio-venous oxygen difference (avDO2) and oxygen extraction ratios were lower when compared to the UPBH group. In spite of a higher final haematocrit of 5% in group 1, in comparison to group 2 with 2%, final muscular oxygen uptake (4.7 +/- 4 vs 10.1 +/- 2 ml.min-1) and mean tPO2 (11.8 +/- 2.3 vs 51.1 +/- 2.9 mm Hg) were lower in group 1 than in group 2. While tPO2 histograms were continuously shifted to lower oxygen tensions during progressive haemodilution with HES, UPBH-exchanged animals showed tPO2 histograms shifted to higher values than baseline. In spite of vasoconstriction, UPBH provided more haemodynamic stability and enhanced skeletal muscle tPO2 during progressive blood exchange when compared to HES.

Critical tissue oxygen tension defines tissue oxygen debt in the isolated hindlimb of the pig during progressive ischemia

To determine a critical skeletal muscle oxygen tension (PO2) value below which a tissue oxygen debt develops. Descriptive study of oxygen transport values in relation to skeletal muscle PO2 throughout progressive ischemia by means of arterial blood flow reductions in an isolated hindlimb model in the pig. Surgical Research department of the University of Amsterdam. Six female Yorkshire pigs weighing 26 to 35 kg (average 33). Controlled blood flow to the isolated hindlimb was achieved by means of extracorporeal circulation. The hindlimb was studied during progressive flow reduction. Oxygen delivery (DO2) and oxygen consumption were calculated as the product of extracorporeal blood flow and, respectively, arterial oxygen content and arterial-venous oxygen content difference. In this fashion, an oxygen supply dependency could be determined in all animals. A critical DO2 value was determined below which a tissue oxygen debt developed. Skeletal muscle PO2 was measured continuously, using a Clark-type polarographic oxygen sensor. Combining the critical DO2 value with the corresponding skeletal muscle PO2 value resulted in a critical skeletal muscle PO2 value of 15.2 +/- 0.4 torr (2.0 +/- 0.1 kPa). In this pig model, a critical skeletal muscle PO2 value could be determined below which a tissue oxygen debt presumably developed.

A NEW SALUTARY RESUSCITATIVE FLUID

Low-volume resuscitation with hypertonic (7.5%) saline (HTS) is an evolving therapeutic modality for patients with hemorrhagic shock. This solution has been shown to exert protective hemodynamic effects in models of controlled hemorrhagic shock and in several clinical trials. However, HTS has no oxygen-carrying capacity and therefore does not improve oxygen delivery directly. One of the leading strategies in developing an oxygen-carrying resuscitative fluid is the encapsulation of hemoglobin within phospholipid vesicles (LEH). This preparation has the advantage of being blood type and antigen free, easily adaptable to scale-up production, and remarkably stable with a long shelf life. We therefore tested the hypothesis that lyophilized LEH reconstituted with HTS will improve tissue oxygenation and survival in rats exposed to a lethal controlled hemorrhagic shock. Shock was induced by withdrawal of 70% of blood volume and therapy (n = 10-16) with HTS (5 mL/kg), LEH (5 mL/kg), lactated Ringer's solution (vol:vol = 1:3), LEH-HTS (5 mL/kg), or oxygen (100%) was initiated 15 minutes later. The LEH-HTS improved skeletal muscle oxygen tension directly measured using a thin-film chamber oxygen sensor (PO2 87 +/- 13 mm Hg vs. 40-50 mm Hg in other groups, p < 0.05). This was associated with improved blood pressure, reduced acidosis, and increased survival at 24 hours (75% vs. 6%-25% in other groups, p < 0.05). In conclusion, the study demonstrates a remarkably salutary effect of LEH reconstituted with HTS as a blood substitute in the treatment of hemorrhagic shock.

Acute effects of ultrasound on skeletal muscle oxygen tension, blood flow and capillary density

The acute effects of pulsed (5 kHz, PRF) ultrasound (2.5 and 5 W/cm 2 SPTA at 1 MHz) on the microvasculature of the rat cremaster were examined. Tissue blood flow, capillary density and PO 2 were measured in both normally perfused and ischemic tissue. Exposure to 2.5 W/cm 2 produced no significant changes in either blood flow or capillary density, however, oxygen tension was significantly reduced in normal tissue at this intensity. Capillary density was significantly diminished in ischemic tissue following exposure to 5 W/cm 2 as was PO 2 in normally perfused tissue. Blood flow was decreased only in the normoxic tissue at 5 W/cm 2. These data suggest that ultrasound at the intensities and frequency employed is capable of producing at least an acute reduction in tissue PO 2.

Microcirculatory hematocrit and blood flow

Direct measurements from many laboratories indicate that the oxygen tension in skeletal muscle is significantly less than in the large veins draining these tissues. Harris (1986) has proposed that because of the parallel anatomic arrangement of large arterioles and venules in skeletal muscle, a counter-current exchange between these vessels can occur. He theorized that diffusion of O2 between arteriole and venule would lower the PO2 in the blood as it enters capillaries and result in a decreased tissue PO2 and an increase in large vein PO2. Calculations (Appendix) show that the amount of O2 transferred between arteriole and venule is inadequate to account for this difference in PO2 between tissue and veins due to the small surface area that is involved. It is well documented that the microcirculatory hematocrit ranges between 20 and 50% of that in the supply vessels. The reduced hematocrit lowers the oxygen content in these vessels and results in a low oxygen tension in the surrounding tissue. True arteriovenous shunts are not present in most skeletal muscles, but 15-20% of the microvessels represent thoroughfare or preferential flow channels. It is suggested that these vessels contain a greater than normal hematocrit to account for a conservation of red cell mass across the microcirculation. Furthermore, it is shown that the hematocrit in the preferential flow channels is an inverse function of the flow rate for any level of the microcirculatory hematocrit. The increased hematocrit raises the flow resistance in these vessels which reduces flow further and represents a positive feedback condition which may contribute to the intermittent and uneven flow patterns which are present within the microcirculation.(ABSTRACT TRUNCATED AT 250 WORDS)

Skeletal muscle PO2: indicator of peripheral tissue perfusion in haemorrhagic shock.

The following conclusions can be made on the basis of this work: 1) Measurements of skeletal muscle oxygen tension provide an excellent index of tissue perfusion in haemorrhagic shock. 2) Correction of cardiac output and arterial blood oxygen tension in haemorrhagic shock does not necessarily ensure normal tissue oxygenation. 3) In haemorrhagic shock adequate replacement of blood loss using a balanced salt solution in addition to blood replacement is an integral part of the fluid management. 4) Correction of hypovolemia with an equivalent volume of a plasma expander and subsequent reinfusion of shed blood also returns tissue perfusion to normal. However, this treatment results in marked haemodilution and correction of extracellular fluid loss remains inadequate.

Oxygen tension in skeletal muscle of unanesthetized rats during hypothermia

Oxygen tension in skeletal muscle of unanesthetized rats during hypothermia

A microelectrode for measuring intracellular PO2.

A simple and reliable method of constructing an intracellular pH microelectrode is described. Antimony is used as the pH sensor. Antimony electrodes have been used in biological systems as early as 1927 (1). Since then several investigators have used different kinds of Sb electrodes. Roos and Boton (3) describe the latest methods of construction and application of pH sensitive micro-electrodes. In most cases the pH electrodes were fabricated by pulling glass capillaries filled with molten antimony and in a few cases by coating glass with antimony. The electrodes were of the open type.

SKELETAL MUSCLE OXYGEN TENSION AND METABOLISM DURING HEMORRHAGIC HYPOTENSION AND SUB-SEQUENT VASOPRESSOR ADMINISTRATION

SKELETAL MUSCLE OXYGEN TENSION AND METABOLISM DURING HEMORRHAGIC HYPOTENSION AND SUB-SEQUENT VASOPRESSOR ADMINISTRATION

Skeletal-muscle oxygen tension and metabolism during induced hypotension and during vasopressor administration.

Skeletal-muscle oxygen tension and metabolism during induced hypotension and during vasopressor administration.