Muscle Tissue PO2 Research Articles

Treatment of Hypotension with Phenylephrine Increases Cerebral Microvascular Perfusion in a Rat Model of Acute Hemodilution

Intraoperative blood loss is associated with reduced mean arterial blood pressure (MAP), which may endanger vital organ perfusion, including the brain. Phenylephrine (PE), an α1-receptor agonist, is clinically utilized to treat intraoperative hypotension through vasoconstriction of resistance arterioles. Clinical studies suggest that raising MAP with PE may decrease perfusion to vital organs such as the brain. Experimental studies suggest that lower α-receptor density in the cerebral resistance arteries may lead to preserved brain perfusion after PE administration. We hypothesize that treatment of hypotension with PE will result in preserved brain perfusion due to different microvascular blood flow and tissue oxygen tension (pO2) responses in the brain and skeletal muscle in an experimental rat model. With Animal Care and Use Committee approval in accordance with ARRIVE-2 guidelines, spontaneously breathing anesthetized rats (1.5% isoflurane) underwent hemodilution by exchanging 40-50% estimated blood volume 1:1 with saline over 10 minutes to achieve a 10-20 mmHg drop in MAP. MAP (tail artery) was measured continuously. Hypotension was treated with PE (10-20 μg/kg/min iv) to increase MAP to a target above baseline MAP. Shed blood was re-infused after stopping the PE infusion. Microvascular blood flow (Oxyflo; Oxford Optronix, Oxford, UK, n=7) or microvascular pO2 (OxyLED, Oxyphor G4, Oxygen Enterprises Ltd., Philadelphia, PA, n=6) were measured continuously in the cerebral cortex (burr hole) and biceps femoris muscle simultaneously in each rat. Results were analyzed via one or two-way ANOVA, with significance achieved at p<0.05. Baseline and post-hemodilution MAP values were comparable in both groups. PE infusion increased MAP to a mean level near 100 mmHg in both groups (p<0.05). Microvascular blood flow and tissue pO2 were greater in the brain as compared to the muscle at all time points (p<0.01 for both). PE infusion resulted in an increase in cerebral microvascular blood flow from baseline (1465±689 vs. 687±453 blood perfusion units (BPU); p<0.001) that was sustained after discontinuing PE and during blood reinfusion. No changes in muscle microvascular flow were observed after PE infusion (294±129 vs. 168±113 BPU). A sustained increase in cerebral microvascular pO2 was measured following PE infusion (50.2±8.6 vs. 40.6±4.6 mmHg; p=0.02), whereas muscle tissue pO2 did not change (22.2±5.6 vs. 25.0±2.5 mmHg). A differential blood flow and microvascular pO2 response was observed following PE infusion in brain and skeletal muscle. Both cerebral microvascular blood flow and tissue pO2 demonstrated sustained increases after PE infusion. By contrast, no changes were observed in muscle microvascular blood flow and pO2. These results suggest that treatment of hypotension with PE administration preferentially increased cerebral vs. muscle perfusion in an experimental model of acute blood loss and fluid resuscitation. Canadian Anesthesiologists’ Society and University of Toronto Merit Award Support. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Model‐based analysis of microcirculatory parameters affecting O 2 transport in skeletal muscle subjected to fixed surface PO 2

Microcirculation in skeletal muscle determines both blood flow distribution and O2 transport. The partial pressure of oxygen (PO2) is a prime candidate to assess in tissue, as PO2 variations herald a functionality decline in skeletal muscle. Traditional non-invasive microcirculatory techniques such as Intra-vital Video Microscopy (IVVM) allowing for blood velocity and capillary saturation (SO2) measurements, are unable to directly assess skeletal muscle tissue PO2. Instead, modern microcirculatory O2 analysis relies on biophysical models to recreate tissue PO2 distributions. (Ellis et al, Microcirc 2012, 19:5). Recently, a continuous coupled partial differential equation (PDE) model of two layers of skeletal muscle coupled via diffusion at their boundaries was developed accounting for tissue O2 diffusion, capillary O2 convection, tissue O2 consumption, and capillary-tissue O2 transfer. This model was developed to study an IVVM protocol involving a controlled exposure of skeletal muscle using an O2 exchange chamber. In the protocol studied, hemodynamic parameters in the skeletal muscle region near to the O2 chamber are experimentally shown to exhibit substantial variations. The prevailing theory is capillary perfusion limits the depth of penetration of the chamber O2, and local hemodynamic parameter responses serve to regulate capillary SO2 in skeletal muscle; this would be towards either a fixed target value or homogeneity with neighboring capillary modules. The coupled PDE two-layer model was developed for steady-state PO2 distributions and was solved using traditional math techniques such as operator decoupling and Fourier decomposition, and exhibited the ability to rapidly and accurately calculate PO2 distributions in skeletal muscle which agreed with experimental values. (Afas and Goldman, Vasc Bio 2020). The solution affords for the unique ability not allowed in previous convection-diffusion analytic models of O2 transport, to observe the interaction of both skeletal muscle layers. This is achieved by assuming baseline hemodynamic parameters in the layer far from the O2 chamber and allowing the near layer to take on a range of parameter variations; these variations can be compared to experimental observations. In this study, the behavior of both layers of skeletal muscle adjacent to an O2 chamber will be modelled by the a-priori fixing of parameters in the region far from the O2 chamber and allowing near-layer parameters to be perturbed. Several parameters, including capillary density φ, velocity vB, inlet saturation SIN, hematocrit HT, and tissue consumption μ will have this variation method applied from previous baselines (Afas et al, Math Biosci 2021, in press), and the resultant two-layer O2 profiles will be visualized, as well as the conditions under which the capillary SO2 is homogenized in both layers of skeletal muscle.

Exchange transfusion with synthetic oxygen‐carrying plasma protein “albumin‐heme” into an acute anemia rat model after seventy‐percent hemodilution

Recombinant human serum albumin (rHSA) incorporating the synthetic heme "albumin-heme" is an oxygen-carrying plasma protein that has the potential to be a red blood cell substitute. The physiological responses to a 30% exchange transfusion with two types of albumin-heme (rHSA-FecycP, rHSA-FepivP) solutions after 70% isovolemic hemodilution with 5 g/dL rHSA were investigated using anesthetized rats. The circulation parameters, blood parameters, renal cortical oxygen pressure (pO2), and muscle tissue pO2 were carefully monitored for 60 min after the injection. The declined mean arterial pressure and the mixed venous partial pO2 significantly recovered to 70.8 and 91.9% of the basal values by intravenous infusion of albumin-hemes, respectively. The lowered renal cortical pO2 also increased, indicating oxygen transport by this synthetic hemoprotein. The administration of albumin-heme into the acute anemia rat model after hemorrhage improved the circulatory volume and resuscitated the shock state. Both rHSA-FecycP and rHSA-FepivP transported oxygen through the body.

SUPPLEMENTAL OXYGEN ADMINISTRATION DURING ISOFLURANE ANESTHESIA INCREASES SKELETAL MUSCLE OXYGEN TENSION

S152 INTRODUCTION: The major defense against surgical wound infections is oxidative killing by neutrophils. [1] Therefore, perioperative supplemental oxygen administration may decrease the incidence of wound infections, which has been confirmed in a bacteria-infection model in pigs. [2] However, tissue oxygen availability in humans is a complex function of arterial oxygen tension and local blood flow. Increased arterial oxygen tension (hyperbaric oxygenation) in critically ill patients without anesthesia is associated with increased systemic vascular resistance [3] and peripheral vasoconstriction [4] resulting in a reduction of tissue oxygen supply. [5] Because administration of volatile anesthetics are generally associated with peripheral vasodilation, it is likely that supplemental oxygen administration during isoflurane anesthesia may increases tissue oxygen tension. METHODS: After IRB approval and consent, we studied patients undergoing elective colon surgery. They were anesthetized with isoflurane, and randomly assigned to or 80% (Group 1; n=10) 30% (Group 2; n=8) inspired oxygen in nitrogen during surgery. Perioperative anesthetic, fluids, and blood transfusion management were determined by protocol. Skeletal muscle tissue oxygen tension was measured by an automatically stepwise driven polarographic needle probe (Eppendorf-pO2-Histograph) placed in the quadriceps muscle. Arterial pO2 was measured from arterial blood probes. All measurements were determined 15 min after induction of anesthesia (30% inspired oxygen) and postoperatively during 1.0% endexspired isoflurane concentration (30% versus 80% inspired oxygen). Results were compared using ANOVA, Mann-Whitney-U and Wilcoxon. Rank-Test-Test. RESULTS: After induction of anesthesia baseline arterial PO2 and tissue oxygen tension (tPO2) did not differ between groups. Postoperative arterial oxygen tension was significantly greater in patients given 80% than 30% oxygen (349 +/- 77 vs. 114 +/- 36 mmHg; p<0.001). The mean tPO2 was also significantly higher during administration of 80% than 30% oxygen (group 1 vs. group 2: 48 mmHg vs. 24 mmHg; p<0.001). The pooled histograms showed a shift to the right toward higher oxygen tensions during 80% oxygen administration. Postoperative muscle tissue PO2 values below 10 mmHg were significantly reduced in group 1 when compared to the baseline and group 2 (p<0.01). DISCUSSION: Our data indicate that supplemental oxygen administration during isoflurane anesthesia increases skeletal muscle tissue oxygen tension. Because the first few hours following bacterial contamination constitute a decisive period during which infection is established, [6] supplemental oxygen administration during isoflurane anesthesia may reduce the wound infection rate.

Optimal hematocrit in patients with peripheral occlusive arterial disease (POAD): Exercise induced muscle tissue pO2 after isovolemic hemodilution

Optimal hematocrit in patients with peripheral occlusive arterial disease (POAD): Exercise induced muscle tissue pO2 after isovolemic hemodilution

Gut and muscle tissue P o2 in endotoxemic dogs during shock and resuscitation : J Appl Physiol 1994; 76/2 (793–800)

There is indirect evidence that tissue hypoxia occurs in human sepsis and surface measures of muscle tissue PO2 (PtiO2) in hypodynamic endotoxic animals are decreased. This study assessed systemic and regional tissue oxygenation in a more relevant model of hyperdynamic endotoxicosis. We isolated venous outflow from the left hindlimb and a segment of ileum in six anesthetized dogs to measure muscle and gut O2 delivery and uptake (VO2) and lactate flux, gut intramucosal pH (pHi) by tonometry, and PtiO2 by multi-point surface electrodes placed on mucosal and serosal surfaces of gut and on muscle. We then infused Escherichia coli lipopolysaccharide (LPS; 2 mg/kg) over 1 h followed by a 2-h infusion of dextran (0.5 ml.kg-1.min-1). LPS infusion significantly decreased systemic and gut VO2, cardiac output (Q), and blood pressure and increased arterial lactate and gut lactate flux. Resuscitation increased Q to above baseline and restored systemic VO2. In response to LPS and then resuscitation, muscle PtiO2 distribution did not change, suggesting little microcirculatory disturbance, although mean PtiO2 first decreased and then increased. In contrast, gut VO2 and pHi remained low and lactate output remained high, despite restoration of gut blood flow. Gut VO2, lactate flux, pHi, and PtiO2 histograms were consistent with a marked redistribution of blood flow within the gut wall, away from the mucosa and toward the muscularis. These data show that, in hyperdynamic acute endotoxemia, skeletal muscle PtiO2 and VO2 are well maintained, but blood flow within the gut is significantly disturbed with mucosal hypoxia.

Gut and muscle tissue PO2 in endotoxemic dogs during shock and resuscitation

There is indirect evidence that tissue hypoxia occurs in human sepsis and surface measures of muscle tissue PO2 (PtiO2) in hypodynamic endotoxic animals are decreased. This study assessed systemic and regional tissue oxygenation in a more relevant model of hyperdynamic endotoxicosis. We isolated venous outflow from the left hindlimb and a segment of ileum in six anesthetized dogs to measure muscle and gut O2 delivery and uptake (VO2) and lactate flux, gut intramucosal pH (pHi) by tonometry, and PtiO2 by multi-point surface electrodes placed on mucosal and serosal surfaces of gut and on muscle. We then infused Escherichia coli lipopolysaccharide (LPS; 2 mg/kg) over 1 h followed by a 2-h infusion of dextran (0.5 ml.kg-1.min-1). LPS infusion significantly decreased systemic and gut VO2, cardiac output (Q), and blood pressure and increased arterial lactate and gut lactate flux. Resuscitation increased Q to above baseline and restored systemic VO2. In response to LPS and then resuscitation, muscle PtiO2 distribution did not change, suggesting little microcirculatory disturbance, although mean PtiO2 first decreased and then increased. In contrast, gut VO2 and pHi remained low and lactate output remained high, despite restoration of gut blood flow. Gut VO2, lactate flux, pHi, and PtiO2 histograms were consistent with a marked redistribution of blood flow within the gut wall, away from the mucosa and toward the muscularis. These data show that, in hyperdynamic acute endotoxemia, skeletal muscle PtiO2 and VO2 are well maintained, but blood flow within the gut is significantly disturbed with mucosal hypoxia.

The influence of flow redistributions on the calculated pO2 in rat heart tissue.

Calculations of muscle tissue pO2 from models that take into account realistic geometrical capillary distributions have shown a resulting considerable range in pO2 values (broad histograms), due to the heterogeneity in capillary spacing. In these models, however, only few selected blood flow types were considered, most often, equal flow through each capillary. The question is addressed here, what the influence is of different flow patterns on calculated tissue pO2 and particularly whether the resulting pO2 histograms can be made more uniform, i.e., less variation in pO2 values.KeywordsExtraction PressureCountercurrent FlowSupply AreaCapillary SpacingBasic HistogramThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Beyond the lung: oxygen delivery and tissue oxygenation.

Beyond the lung: oxygen delivery and tissue oxygenation.

Exercise-Induced Variations in Muscle Tissue Oxygen Pressure in Claudicants: Effects of Buflomedil

The amount of oxygen actually supplied to the ischemic muscle tissue of patients with intermittent claudication was quantified before and after a standardized pedal ergometric test. Muscle tissue pO2 was measured with micro-platin needle electrodes directly in the lower limb muscles at rest and 3, 10, 20 and 60 min after a 4-min work load. Time-dependent variations in the behavior of pO2 values as well as changes in the shapes of pooled pO2 histograms make it possible to monitor the effect of therapeutic measures. In claudicants (stage IIb) with ascertained occlusions or stenosis of the femoral artery or the pelvis region, it was demonstrated that the delayed increase in tissue pO2 after exercise could be improved by the infusion of 400 mg buflomedil. Comparison between the time-related pooled histograms confirmed improvement of oxygen supply under the influence of this drug.

Rabbit Skeletal Muscle PO2 during Hypodynamic Sepsis

We measured skeletal muscle tissue PO2 (PtO2) in anesthetized rabbits (n = 7) following infusion of an intravenous bolus of E coli endotoxin. An array of surface PO2 microelectrodes was placed over the hindlimb biceps femoris muscle and sufficient readings were obtained to construct a PtO2 histogram. Changes in the histogram standard deviation were used to characterize micro-circulatory maldistribution. Systemic O2 consumption (VO2) was measured by the expired gas method. Cardiac output (Q) and systemic O2 transport (TO2) were calculated. Samples of arterial, right atrial (ra), and hindlimb venous blood, from a catheter placed in the infrarenal portion of the vena cava, were simultaneously obtained for measurement of blood gases and saturations. Following the administration of endotoxin, there were decreases in Q and TO2 of approximately 50 percent. The VO2 initially decreased 23 percent, but returned to baseline levels 30 minutes after endotoxin administration. Systemic O2 extraction ratio (ERO2 = VO2/TO2) increased from 0.32 +/- .03 to 0.54 +/- .07 (p less than 0.01), whereas hindlimb ERO2 increased from 0.42 +/- .03 to 0.60 +/- .02 (p less than 0.01). The arithmetic mean of the PtO2 histograms decreased after endotoxin infusion (43 +/- 4 to 7 +/- 2 mm Hg; p less than 0.01), but PLO2 remained at baseline levels (35 +/- 2 vs. 33 +/- 2 mm Hg; p = NS). The standard deviation of the PtO2 histograms remained constant during the experiment. This finding supports the notion that skeletal muscle microcirculatory heterogeneity does not increase during endotoxin induced hypodynamic sepsis.

Buffering of muscle tissue PO2 levels by the superposition of the oxygen field from many capillaries.

High resolution measurement in both exercised skeletal and cardiac tissue made radially outward from capillaries and longitudinally parallel to capillaries by Gayeski and Honig (1986, 1986a,b) and Honig and Gayeski (1987) indicate shallow variation of tissue PO2 and the absence of strong causal relation between the PO2 at a point and the proximity of that point to the nearest active capillary. Proposed as a model for the analysis of this tissue PO2 distribution, so contrary to the expectations of Krogh type models, are a class of multicellular tissue cylinder models. Each cylinder is penetrated by many parallel capillaries. In order to better represent the natural irregularities of the skeletal and cardiac tissue both with regard to radial placement and the stagger of the capillary inlets, the following types of models both with and without yoglobin are examined: regular square arrays where the capillary PO2 levels are random, uniform capillary PO2 levels but random capillary positions, and those with both the capillary PO2 levels and the positions are random. The results of the model calculations show that the superposition of the oxygen diffusion fields of all the capillaries produce a tissue PO2 distribution with the properties: (1) lower tissue PO2 levels than those predicted by Krogh theory, (2) significant non-local contributions to the PO2 at a point in the tissue which greatly reduces this correlation between PO2 at a point and its proximity to an active capillary, (3) shallow transcellular PO2 variation.

Tissue PO2 and arteriolar responses to metabolic stimuli during maturation of striated muscle.

Tissue O2 tension (PO2) and small arteriolar diameter were measured in hamsters aged 32, 60, and 80 days. The cremaster muscle was isolated and superfused with a solution equilibrated with 0, 5, or 10% O2 stimulated to contract at 1 Hz. Resting muscle tissue PO2 was proportional to superfusate PO2 and was not different between age groups. The decrease in tissue PO2 during contraction was greatest in adult animals when the superfusate PO2 was low but was equal in all groups when the superfusate PO2 was high. Elevated superfusate PO2 was correlated with a vasoconstriction, the magnitude of which varied inversely with age. Resting and contraction-induced vascular diameter were largest in the youngest animals, relative to maximum diameter, but absolute resting and contraction-induced diameters were similar in all groups. We suggest that tissue PO2 at rest was similar because of an age-associated decrease in fiber O2 consumption to maintain a constant proportionality between O2 supply and demand. The relative stability of tissue PO2 during contraction in young animals might have reflected superior regulation. However, a simple numerical analysis predicts smaller tissue PO2 decreases during contraction in young animals because of short intercapillary distances and other altered O2 supply parameters, even if regulation had been identical in all age groups.

Role of oxygen in arteriolar functional vasodilation in hamster striated muscle.

Small isolated groups of striated muscle cells were stimulated in the hamster cremaster muscle. During and after stimulation, oxygen microelectrodes were employed to determine the relationships among arteriolar vasodilation, tissue Po2, and periarteriolar Po2. Localized contraction produced a biphasic arteriolar vasodilation without associated alteration of Po2 on the surface of the arterioles (vascular smooth muscle Po2). In contrast, muscle contraction produced a decline in muscle tissue Po2 that was proportional to the contraction frequency over the range of 1--4 contractions per second. An increase in contraction frequency also produced a graded increase in arteriolar diameter, the magnitude of which was statistically correlated with the steady-state change in tissue Po2. However, arteriolar diameter changes preceded tissue Po2 changes, both with the initiation of functional dilation and during the recovery period. Tissue Po2 was manipulated at rest and during contraction by increasing the Po2 of the superfusion solution. Increasing the tissue Po2 caused a decrease in vascular diameter under both conditions and a reduction in the magnitude of the arteriolar vasodilation during contraction. Restoration of tissue Po2 to resting levels during muscle contraction produced only partial restoration of vascular diameters. The results are consistent with the hypothesis that at least three components are involved in the vascular control process during muscular activity: an early component independent of tissue oxygen levels, a late component independent of oxygen, and a late component associated with a decrease in muscle Po2, without an effect on vascular smooth muscle Po2. The evidence indicated that Po2 of the smooth muscle of the arterioles had no role in the dilation observed.

Oxygen Pressure in Ischemic Muscle Tissue of Patients With Chronic Occlusive Arterial Diseases

Local tissue oxygen pressure was measured with micro-Pt-electrodes in the resting tibialis anterior muscles of 10 patients with chronic occlusive arterial disease and in 9 healthy subjects. The mean pO2 values in the patient group was 13.3 +/- 5.4 Torr, and 27.2 +/- 4.4 Torr in the control group. The difference is highly statistically significant. Preliminary results of treatment of 10 patients with the rheologically-active drug Ancrod show a statistically significant increase of oxygen pressure in the ischemic muscle tissue. Measurement of muscle tissue pO2 with microelectrodes seems to be an objective and quantitative method to investigate the oxygen supply to ischemic muscles and to judge the effects of therapeutic measures.