Increased hemoglobin O2 affinity does not improve O2 consumption in hypoxemia

We perfused an isolated rabbit hindlimb preparation with suspensions of human erythrocytes (RBC) having different O2 affinities. Our objective was to compare the effect of changes in P50, the PO2 at which hemoglobin is 50% saturated, on tissue O2 consumption during severe hypoxemia. A high-affinity (HA) group (n = 9) was perfused with RBC incubated in NaCNO (P50 = 21.4 +/- 1.9 Torr). This was compared with a low-affinity (LA) group (n = 9) perfused with rejuvenated RBC (P50 = 31.1 +/- 1.8 Torr). The arterial PO2 of the perfusate was decreased to approximately 24 Torr in both preparations. Perfusion flow and hemoglobin concentration were maintained constant. During hypoxemia arterial O2 saturation and total O2 transport (TO2) were greater in the HA than the LA group (P less than 0.05). O2 consumption and effluent venous PO2 decreased with hypoxemia in both groups to similar levels. Consequently, the LA group showed a greater O2 extraction ratio than the HA group (P less than 0.05). The ratio of phosphocreatine to inorganic phosphate, measured with 31P magnetic resonance spectroscopy, decreased at a comparable rate in both groups. As shown by a mathematical model of peripheral O2 transport, these experimental results can be explained on the basis of peripheral limitation to O2 diffusion. We conclude that increased hemoglobin affinity does not appreciably improve tissue oxygenation in hypoxemia, since the increase in TO2 is offset by diffusion limitation at the tissues.     

Role of 20-HETE in the pial arteriolar constrictor response to decreased hematocrit after exchange transfusion of cell-free polymeric hemoglobin.

The cerebrovascular response to decreases in hematocrit and viscosity depends on accompanying changes in arterial O2 content. This study examines whether 1) the arteriolar dilation seen after exchange transfusion with a 5% albumin solution can be reduced by the K(ATP) channel antagonist glibenclamide (known to inhibit hypoxic dilation), and 2) the arteriolar constriction seen after exchange transfusion with a cell-free hemoglobin polymer to improve O2-carrying capacity can be blocked by inhibitors of the synthesis or vasoconstrictor actions of 20-HETE. In anesthetized rats, decreasing hematocrit by one-third with albumin exchange transfusion dilated pial arterioles (14 +/- 2%; SD), whereas superfusion of the surface of the brain with 10 muM glibenclamide blocked this response (-10 +/- 7%). Exchange transfusion with polymeric hemoglobin decreased the diameter of pial arterioles by 20 +/- 3% without altering arterial pressure. This constrictor response was attenuated by superfusing the surface of the brain with a 20-HETE antagonist, WIT-002 (10 microM; -5 +/- 1%), and was blocked by two chemically dissimilar selective inhibitors of the synthesis of 20-HETE, DDMS (50 microM; 0 +/- 4%) and HET-0016 (1 microM; +6 +/- 4%). The constrictor response to hemoglobin transfusion was not blocked by an inhibitor of nitric oxide (NO) synthase, and the inhibition of the constrictor response by DDMS was not altered by coadministration of the NO synthase inhibitor. We conclude 1) that activation of K(ATP) channels contributes to pial arteriolar dilation during anemia, whereas 2) constriction to polymeric hemoglobin transfusion at reduced hematocrit represents a regulatory response that limits increased O2 transport and that is mediated by increased formation of 20-HETE, rather than by NO scavenging.     

PO2 profiles near arterioles and tissue oxygen consumption in rat mesentery

A scanning phosphorescence quenching microscopy technique, designed to prevent accumulated O(2) consumption by the method, was applied to Po(2) measurements in mesenteric tissue. In an attempt to further increase the accuracy of the measurements, albumin-bound probe was topically applied to the tissue and an objective-mounted pressurized bag was used to reduce the oxygen transport bypass through the thin layer of fluid over the mesentery. Po(2) was measured at multiple sites perpendicular to the blood/wall interface in the vicinity of 84 mesenteric arterioles (7-39 microm in diameter) at distances of 5, 15, 30, 60, 120, and 180 microm in seven anesthetized Sprague-Dawley rats, thereby creating Po(2) profiles. Interstitial Po(2) above and immediately beside arterioles was found to agree with known intravascular values. No significant difference in Po(2) profiles was found between small and large arterioles, indicating a small longitudinal Po(2) gradient in the precapillary mesenteric microvasculature. In addition, the Po(2) profiles were used to calculate oxygen consumption in the mesenteric tissue (56-65 nl O(2) x cm(-3) x s(-1)). Correction of these values for contamination with ambient oxygen yielded an oxygen consumption rate of 60-68 nl O(2) x cm(-3) x s(-1), the maximal limit for consumption in the mesentery. The results were compared with measurements made by other workers in regard to the employed techniques.     

Critical O2 delivery to skeletal muscle at high and low PO2 in endotoxemic dogs

An ischemic canine limb model was used to determine whether endotoxin reduces the ability of resting skeletal muscle to extract O2 and whether increasing the arterial PO2 would increase its O2 extraction. Isolated limbs were pump perfused via an extracorporeal circuit with membrane oxygenator at three progressively lower flows and PO2 of both 60 and 200 Torr, whereas the rest of the body remained normoxic and normotensive. Six anesthetized, paralyzed dogs were injected with endotoxin (4 mg/kg, ENDO), and another six were controls (CONT). Limb critical O2 delivery was higher (P less than 0.05) in ENDO than CONT (8.3 vs. 6.1 ml.kg-1.min-1). Critical venous PO2 was also higher (P less than 0.05) in ENDO than CONT (38 vs. 30 Torr). Critical O2 extraction ratio was lower (P less than 0.05) in ENDO than CONT (0.60 vs. 0.73). There were no differences in these variables between low and high arterial PO2. We concluded that 1) endotoxin can cause a small but significant O2 extraction defect in skeletal muscle, 2) increasing arterial PO2 did not correct such a defect, nor did it improve O2 uptake in ischemic, but otherwise healthy, muscle, and 3) skeletal muscle may contribute to the peripheral O2 extraction defect in adult respiratory distress syndrome insofar as endotoxin effects model those found in adult respiratory distress syndrome.     

Oxygen affinity of hemoglobin regulates O2 consumption,metabolism, and physical activity

The oxygen affinity of hemoglobin is critical for gas exchange in the lung and O(2) delivery in peripheral tissues. In the present study, we generated model mice that carry low affinity hemoglobin with the Titusville mutation in the alpha-globin gene or Presbyterian mutation in the beta-globin gene. The mutant mice showed increased O(2) consumption and CO(2) production in tissue metabolism, suggesting enhanced O(2) delivery by mutant Hbs. The histology of muscle showed a phenotypical conversion from a fast glycolytic to fast oxidative type. Surprisingly, mutant mice spontaneously ran twice as far as controls despite mild anemia. The oxygen affinity of hemoglobin may control the basal level of erythropoiesis, tissue O(2) consumption, physical activity, and behavior in mice.     

Effect of phentolamine on the relationship between O2 consumption and delivery in sheep.

The oxygen flux challenge test (OFT) has recently been used in critically ill patients as a dynamic test for assessment of the response in oxygen consumption (VO2) to an increase in O2 delivery (QO2). Such a test may indicate whether a patient demonstrates delivery-dependent VO2. However, the increase in whole body VO2 following an increase of QO2 might be due to the agents used for the OFT. In this study, we examined the possibility of obtaining false positive OFT with an alpha-adrenergic antagonist. Five normothermic thiopentone-anaesthetised and mechanically-ventilated (inspired O2 fraction, 0.3; expired CO2 fraction, 0.045-0.055) adult sheep (25-31 kg) were investigated. The QO2 was increased in a stepwise fashion from 200 to 850 ml.min-1 by vasodilatation with intravenous infusion of phentolamine. The VO2 was calculated at each step from the product of arteriovenous. O2 content difference (CO2, a-v) and cardiac output (Qc), the latter being continuously measured with a transit-time ultrasonic flow probe placed around the main pulmonary artery. The VO2 (y) was linearly related to QO2 (x), y = 0.034 (SD 0.024) x + 29.3 (SD 3.9). The relationship between Qc (y) and CO2, a-v (x) was y = 4.6x(-1.12) (n = 69; r2 = 0.75; P = NS compared to the expected relationship for isoconsumption conditions, i.e. where Qc = VO2.(CO2, a-v)(-1). Our data suggested that under stable conditions, an infusion of phentolamine did not sufficiently alter the relationship between Qc and CO2, a-v to invalidate its use for OFT in normal sheep.     

Effect of decreased O2 supply on skeletal muscle oxygenation and O2 consumption during sepsis: role of heterogeneous capillary spacing and blood flow

One of the main aspects of the initial phase of the septic inflammatory response to a bacterial infection is abnormal microvascular perfusion, including decreased functional capillary density (FCD) and increased blood flow heterogeneity. On the other hand, one of the most important phenomena observed in the later stages of sepsis is an increased dependence of tissue O(2) utilization on the convective O(2) supply. This "pathological supply dependency" is associated with organ failure and poor clinical outcomes. Here, a detailed theoretical model of capillary-to-tissue O(2) transport during sepsis is used to examine the origins of abnormal supply dependency. With use of three-dimensional arrays of capillaries with heterogeneous spacing and blood flow, steady-state O(2) transport is simulated numerically during reductions in the O(2) supply. Increased supply dependency is shown to occur in sepsis for hypoxic (decreased hemoglobin O(2) saturation) and stagnant (decreased blood flow) hypoxia. For stagnant hypoxia, a reduction in FCD with decreasing blood flow is necessary to obtain the observed increase in supply dependency. Our results imply that supply dependency observed under normal conditions does not have its origin at the level of individual capillaries. In sepsis, however, diffusion limitation and shunting of O(2) by individual capillaries occur to a degree that is dependent on the heterogeneity of septic injury and the arrangement of capillary networks. Thus heterogeneous stoppage of individual capillaries is a likely factor in pathological supply dependency.     

Effects of malaria on O2 consumption and brown adipose tissue activity in mice

Increased energy expenditure often occurs during illness or after injection of endotoxin and can contribute to the generation of fever. In laboratory rats and mice the thermogenic response has been attributed to the sympathetic activation of brown adipose tissue (BAT), although mice often fail to show pyrexia. In this study the effects of malaria on O2 consumption and BAT were studied in mice inoculated with Plasmodium berghei. Parasitemia was maximal (greater than 50% of erythrocytes showing positive Leishman staining) 72 h after inoculation. Up to this time body weight and food intake were similar to values for control mice, although colonic temperatures were slightly depressed in infected mice. Thereafter, infected mice showed marked hypophagia, loss of body weight, and severe hypothermia; colonic temperature was less than 31 degrees C at 96 h when the experiment was terminated. Resting O2 consumption (VO2) measured at 24 degrees C was slightly elevated in infected mice 12 h after inoculation and reached a peak value (31% above controls) at 48 h. VO2 returned to the same value as controls at 96 h. In vitro thermogenic activity of BAT (assessed from binding of guanosine diphosphate to isolated mitochondria) was not significantly altered in infected mice. These data demonstrate a marked thermogenic response to malarial infection, but this is not accompanied by fever in mice and is dissociated from stimulation of BAT activity.     

Increased VO2 max with right-shifted Hb-O2 dissociation curve at a constant O2 delivery in dog muscle in situ

If the diffusive component ofO₂ transport in muscle isimportant in determining exercise capacity, an increasedcapillary-to-tissue PO₂ differenceshould enhance gas exchange from blood to skeletal muscle duringexercise. Thus a rightward shift in theO₂ dissociation curve shouldtheoretically increase O₂extraction and improve maximal O₂uptake (O_{2 max}). Totest this hypothesis, we used the canine gastrocnemius muscle to studymaximal exercise in eight dogs at a normalP₅₀ (33.1 ± 0.4 Torr) and withthe O₂ dissociation curve shifted to the right by anallosteric modifier of hemoglobin (Hb) (methylpropionic acid, RSR-13;P₅₀ = 53.2 ± 5.0 Torr). Fourcontrol dogs were also studied before and after infusion of vehicle.O₂ (100%) was inspired duringexercise to maintain arterial saturation in both conditions. The musclewas surgically isolated and electrically stimulated (tetanic train: 0.2-ms stimuli for 200-ms duration at 50 Hz, once per s). Tomaintain O₂ delivery (pre-RSR-13 = 19.1 ± 2.9; RSR-13 = 19.6 ± 2.5 ml · 100 g¹ · min¹),the muscle was pump perfused. At a constantO₂ delivery, RSR-13 significantlyincreased percent O₂ extraction(pre-RSR-13 = 61 ± 4.0; RSR-13 = 75.5 ± 4.7) andmuscle O_{2 max}(pre-RSR-13 = 11.8 ± 2.1; RSR-13 = 14.2 ± 1.5 ml · 100 g¹ · min¹).This improvement inO_{2 max} with increasedP₅₀ demonstrates itsO₂ supply dependence whenP₅₀ is normal and the importance of O₂ diffusive transport tomuscle at maximal exercise.

     

Oxygen delivery and consumption in the microcirculation after extreme hemodilution with perfluorocarbons

The oxygen transport capacity of fluorocarbons was investigated in the hamster chamber window model microcirculation to determine the rate at which oxygen is delivered to the tissue in conditions of extreme hemodilution [hematocrit (Hct) 11%]. Hydroxyethlyl starch (HES 200; 200 kDa molecular mass) was used as a plasma expander for two isovolemic hemodilutions performed with 10% HES 200 until a Hct of 65%. A third step reduced the Hct to 75% of baseline and was performed with either HES 200 or a 60% perfluorocarbon (PFC) emulsion. Comparisons of HES 200-only-hemodiluted animals versus 4.2 g/kg PFC emulsion-hemodiluted animals were made at 21% and 100% normobaric oxygen ventilation. It was found that systemic and microvascular oxygen delivery was 25% and 400% higher in the PFC animals compared with HES 200 animals, respectively, showing that PFCs deliver oxygen to the tissue when combined with hyperoxic ventilation in the present experiments, with no evidence of vasoconstriction or impaired microvascular function. Oxygen ventilation (100%) led to a positive base excess for the PFC group (5.5 +/- 2.5 mmol/l) versus a negative balance (-0.8 +/- 1.4 mmol/l) for the HES 200 group, suggesting that microvascular findings corresponded to systemic events.     

Regional myocardial perfusion under exchange transfusion with liposomal hemoglobin: in vivo and in vitro studies using rat hearts

The purpose of this study was to test the hypothesis that exchange transfusion with liposomal hemoglobin (LH) reduces the microheterogeneity of regional myocardial flows while sustaining cardiac function. Neo Red Cell mixed with albumin was used as the LH solution, in which the LH volume fraction was 17 approximately 18% and hemoglobin density was nearly two-thirds smaller than in rat blood. Regional myocardial flows in left ventricular free walls were measured by tracer digitalradiography (100-mum resolution) in anesthetized rats with or without 50% blood-LH exchange transfusion. Within-layer flow distributions showed lower heterogeneity with (n = 8) than without (n = 8) LH transfusion. No extravasation of hemoglobin was confirmed by 3,3-diaminobenzidin staining (n = 2). Carotid flow increased by 68% due to LH transfusion, whereas arterial pressure and heart rate remained unchanged. On the other hand, cross-circulated rat hearts (n = 7) were used to evaluate the effects of 50% blood-LH exchange on coronary flow and tone preservation under 300-beats/min pacing and 100-mmHg perfusion pressure. Blood-LH exchange caused a 71% increase of coronary flow and 10% decrease of percent flow increase during hyperemia after 30-s flow interruption. Myocardial O(2) supply and consumption increased by 9% and 10%, respectively, whereas myocardial O(2) extraction remained unchanged. The large increases of in vivo carotid flow and coronary flow in cross-circulated hearts due to LH coperfusion could be explained by the reduction of apparent flow viscosity. These results suggest that under LH coperfusion, the microheterogeneity of myocardial flows decreases with increased coronary flow while fairly preserving coronary tone and cardiac function.     

Increased aggressive behavior and decreased affiliative behavior in adult male monkeys after long-term consumption of diets rich in soy protein and isoflavones

Estrogen produced by aromatization of gonadal androgen has an important facilitative role in male-typical aggressive behavior that is mediated through its interaction with estrogen receptors (ER) in the brain. Isoflavones found in soybeans and soy-based dietary supplements bind ER and have dose- and tissue-dependent effects on estrogen-mediated responses. Yet, effects of isoflavone-rich diets on social and aggressive behavior have not been studied. We studied the effects of long-term (15 months) consumption of diets rich in soy isoflavones on spontaneous social behavior among adult male cynomolgus macaques (Macaca fascicularis) (n = 44) living in nine stable social groups. There were three experimental conditions which differed only by the source of dietary protein: casein and lactalbumin (no isoflavones), soy protein isolate containing 0.94 mg isoflavones/g protein, and soy protein isolate containing 1.88 mg isoflavones/g protein. In the monkeys fed the higher amount of isoflavones, frequencies of intense aggressive (67% higher) and submissive (203% higher) behavior were elevated relative to monkeys fed the control diet (P's < 0.05). In addition, the proportion of time spent by these monkeys in physical contact with other monkeys was reduced by 68%, time spent in proximity to other monkeys was reduced 50%, and time spent alone was increased 30% (P's < 0.02). There were no effects of treatment on serum testosterone or estradiol concentrations or the response of plasma testosterone to exogenous gonadotropin-releasing hormone (GnRH). The results indicate that long-term consumption of a diet rich in soy isoflavones can have marked influences on patterns of aggressive and social behavior.     

Blood volume and cardiac index in rats after exchange transfusion with hemoglobin-based oxygen carriers

Migita, Russell, Armando Gonzales, Maria L. Gonzales, Kim D. Vandegriff, and Robert M. Winslow. Blood volume and cardiac indexin rats after exchange transfusion with hemoglobin-based oxygencarriers. J. Appl. Physiol. 82(6):1995-2002, 1997.We have measured plasma volume and cardiac indexin rats after 50% isovolemic exchange transfusion with humanhemoglobin cross-linked between the -chains withbis(3,5-dibromosalicyl)fumarate (Hb) and with bovine hemoglobinmodified with polyethylene glycol (PEGHb). Hb and PEGHb differ incolloid osmotic pressure (23.4 and 118.0 Torr, respectively), oxygenaffinity (oxygen half-saturation pressure of hemoglobin = 30.0 and 10.2 Torr, respectively), viscosity (1.00 and 3.39 cP, respectively), andmolecular weight (64,400 and 105,000, respectively). Plasma volume wasmeasured by Evans blue dye dilution modified for interference by plasmahemoglobin. Blood volumes in PEGHb-treated animals were significantlyelevated (74.0 ± 3.5 ml/kg) compared with animals treated withHb (49.0 ± 1.2 ml/kg) or Ringer lactate (48.0 ± 2.0 ml/kg) or with controls (58.2 ± 1.9 ml/kg). Heart rate reductionafter Hb exchange is opposite to that expected with blood volumecontraction, suggesting that Hb may have a direct myocardialdepressant action. The apparently slow elimination of PEGHb during the2 h after its injection is a consequence of plasma volume expansion:when absolute hemoglobin (concentration × plasma volume) iscompared for PEGHb and Hb, no difference in their eliminationrates is found. These studies emphasize the need to understand bloodvolume regulation when the effects of cell-free hemoglobin onhemodynamic measurements are evaluated.

     

O2 exchange between blood and brain tissues studied with 18O2 indicator-dilution technique

A technique has been developed to record 18O2 dilution curves of an organ in vivo by use of 51Cr-labeled erythrocytes as a reference tracer. The technique employs anaerobic sampling of venous outflow following an intraarterial injection of tracer-laden blood and off-line determination of [18O2] and [51Cr] profiles in the venous outflow. O2 and reference indicator-dilution curves of cerebral circulation were recorded in eight experiments with six halothane-anesthetized dogs. Autologous blood labeled with the tracers was injected into a carotid artery, and brain venous outflow was sampled from the sagittal sinus. The total net extraction of O2 tracer was equal to the extraction of elemental O2. Instantaneous extraction of 18O2 along the outflow curve fell linearly with time, from an initial value of 0.6-0.7 to very small or even negative values toward the end of a pulse. This indicates that O2 undergoes a flow-limited distribution. In all experiments, the mean transit time of unmetabolized 18O2 was longer than the mean transit time of the Cr tracer. An index of the tissue O2 dilution space, hence the mean tissue PO2, is calculated from this data with the use of a modified central volume principle. This estimate of mean tissue PO2 increases as a linear function of sagittal sinus PO2 with a slope of 0.97. The method may provide an index of the critical PO2 of venous blood, the PO2 below which O2 diffusion from blood to tissue may limit its rate of metabolic uptake.     

CO binding to hemoglobin and myoglobin in equilibrium with a gas phase of low PO2 value

The aim of this paper was to measure the binding of CO to myoglobin and hemoglobin at various PO2 values. For this purpose we have studied an "in vitro" system made up of solutions of hemoglobin and myoglobin equilibrated in two connected tonometers with the same gas phase of various PO2 and PCO. The results indicate that a significant proportion of CO is released by hemoglobin and binds myoglobin at low PO2 values (approximately 2-3 Torr), in qualitative agreement with the predictions of a previous computer simulation of the "in vivo" system.     

Improved embryo development with decreased apoptosis in blastomeres after the treatment of cloned bovine embryos with beta-mercaptoethanol and hemoglobin

In preliminary experiments, the treatment of donor somatic cells with beta-mercaptoethanol (ME) or hemoglobin (Hb) improved in vitro-development of bovine cloned embryos. This study was subsequently evaluated whether the exposure to Hb and/or ME during in vitro-maturation or embryo culture could further promote the development of embryos cloned with ME-treated donor cells. A prospective, randomized study was conducted and, embryo development, cell number, and apoptosis in blastocysts were monitored. A significant (P < 0.05) effect was found after the combined treatment of cloned embryos with Hb (1 microg/ml) and ME (10 microM); the development of morulae (53 vs. 35%) was greatly improved, which resulted in enhanced blastocyst formation (38%). However, cell number and apoptosis in blastocysts were predominantly affected by ME rather than Hb; a significant increase in total cell number of blastomeres (142-154 vs. 123 cells/embryo), inner cell mass (ICM) (39-41 vs. 27), and trophectoderm (TE) (103-114 vs. 98), and the ratio of ICM to TE cell number (0.26-0.27 vs. 0.22) was found. Also, the apoptosis index indicating the ratio of apoptotic cell to normal blastomere number was greatly reduced after ME treatments (0.85 vs. 0.056-0.069). When embryos cloned with ME-treated cells were cultured in Hb + ME-containing medium, any of the treatments to recipient oocytes before enucleation did not further promote the development. In conclusion, combined treatment of cloned embryos with Hb + ME not only improved in vitro-development but also decreased blastomere apoptosis. The use of ME-treated donor cells and the culture of cloned embryos in Hb + ME-containing medium yielded the optimal results for promoting the production of blastocysts with improved quality.     

The ultrastructural picture of cerebral cortex of rat after hypoxia. I. Findings after inhalation of 5% O2 and 95% N2

The ultrastructure of some elements in the motor region of the cerebral cortex of the rat were studied after hypoxia. The experimental animals, after receiving intraperitoneal chloral hydrate anaesthesia, were placed in a chamber with a controlled supply of a mixture of 95% N2 and 5% O2. After 2- and 3-hour exposure to hypoxic conditions the animals were processed for electron optic study. Edematous mitochondria pith partial or total destruction of the mitochondrial matrix were observed. Some mitochondria were changed into large vacuolar formations. The granular endoplasmic reticulum of neurocytes was dilated and in the broad dilatation structures of lamellar shape were sporadically found. The Golgi complex contained vacuoles of different sizes and long cisterns. Hydrated astrocytes were visualized in the neuropil and perivascular astrocyte processes displayed edematous changes. In the group of animals exposed to hypoxia for 3 hours but processed only 24 hours after termination of hypoxia the same changes were observed yet their extent was considerably diminished. This finding indicates that changes induced by hypoxia tend to return to normal conditions.     

Muscle maximal O2 uptake at constant O2 delivery with and without CO in the blood

In the present study we investigated the effects of carboxyhemoglobinemia (HbCO) on muscle maximal O2 uptake (VO2max) during hypoxia. O2 uptake (VO2) was measured in isolated in situ canine gastrocnemius (n = 12) working maximally (isometric twitch contractions at 5 Hz for 3 min). The muscles were pump perfused at identical blood flow, arterial PO2 (PaO2) and total hemoglobin concentration [( Hb]) with blood containing either 1% (control) or 30% HbCO. In both conditions PaO2 was set at 30 Torr, which produced the same arterial O2 contents, and muscle blood flow was set at 120 ml.100 g-1.min-1, so that O2 delivery in both conditions was the same. To minimize CO diffusion into the tissues, perfusion with HbCO-containing blood was limited to the time of the contraction period. VO2max was 8.8 +/- 0.6 (SE) ml.min-1.100 g-1 (n = 12) with hypoxemia alone and was reduced by 26% to 6.5 +/- 0.4 ml.min-1.100 g-1 when HbCO was present (n = 12; P less than 0.01). In both cases, mean muscle effluent venous PO2 (PVO2) was the same (16 +/- 1 Torr). Because PaO2 and PVO2 were the same for both conditions, the mean capillary PO2 (estimate of mean O2 driving pressure) was probably not much different for the two conditions, even though the O2 dissociation curve was shifted to the left by HbCO. Consequently the blood-to-mitochondria O2 diffusive conductance was likely reduced by HbCO.(ABSTRACT TRUNCATED AT 250 WORDS)     

Maternal, fetal, and newborn tissue PO2 in sheep measured with galvanic oxygen electrodes

Tissue PO2 was measured with galvanic oxygen electrodes chronically implanted in maternal and fetal tissues of two pregnant ewes. Labor commenced after 3 days in one ewe and after 11 days in the other. Tissue PO2 was measured in both newborn lambs. Fetal tissue PO2 during labor was less than 3 mm Hg but rose to values similar to those found in adult tissues in the newborn period. Function of the electrode and response of the tissue to change in oxygenation was challenged by administration of 100% oxygen to the pregnant ewe or newborn lamb, and by administration of intravenous epinephrine to the ewe. These tests suggested that all electrodes were functioning satisfactorily in vivo and that tissue PO2 was responding as anticipated. Recalibration of electrodes after removal from the tissues confirmed that their response in vitro was similar to that obtained before implantation.