Tissue O2 Tension Research Articles

A Model of Brain Arteriolar Oxygen and Carbon Dioxide Transport during Anemia

Existing experimental and theoretical evidence suggests that precapillary diffusion of O2 and CO2 occurs between arterioles and tissue under normal physiologic conditions. However, limited information is available on arteriolar gas transport during anemia. With use of a mathematical model of an arteriolar network in brain tissue, anemic hematocrits of 35, 25, and 15% were modeled to determine the effect of anemia on the exchange, the change in the equilibrium tissue O2 and CO2 tensions, and the increase in blood flow needed to restore tissue oxygenation. We found that the blood PO2 exiting the network fell from 66 mm Hg normally to 48 mm Hg during the severest anemia. Concurrently, the equilibrium tissue O2 tensions dropped from 44 to 23 mm Hg. For CO2 the exit blood PCO2 was 58 mm Hg for a 15% hematocrit, an increase of 4 mm Hg from the normal value, and equilibrium tissue PCO2 increased from 56 to 61 mm Hg. Blood flow increases from normal values necessary to offset the effects of the decreased O2 delivery to the tissue were 26, 86, and 222%, respectively, for hematocrits of 35, 25, and 15%. We compared our model results with recent experimental studies that have suggested that the amount of O2 diffusion is much higher than predicted values. We found that these experimental O2 gradients are three to four times larger than theoretical.

New perfluorocarbon emulsion improves tissue oxygenation in cat retina.

We have studied the conditions under which a perfluorocarbon emulsion of perfluorooctyl bromide (PFOB; Alliance Pharmaceutical, San Diego, CA) enhances tissue O2 delivery. Measurements of retinal tissue O2 tension (PO2) were made in anesthetized, artificially respirated, dark-adapted, normovolemic cats before, during, and after the infusion of three successive doses of 1 g PFOB/kg body wt each. There was little immediate effect of the infusion on the tissue PO2 when the cats were breathing room air, but the mean increase in tissue PO2 during 100% O2 breathing was 60 +/- 9% (SE; n = 8 cats) greater after infusion of 1 g PFOB/kg and approximately 136% greater after 3 g PFOB/kg. Similar infusions of the emulsifying medium alone had negligible effects on tissue PO2. These results suggest that PFOB emulsion may be clinically useful in treating tissue hypoxia in normovolemic patients breathing O2-enriched air.

Instabilities of metabolic regulations in aging.

1) That non-invasive NMR and optical methods can a) quantify the work stress on mitochondria for ATP production, and b) indicate the tissue O2 tension in the capillary bed that is responsible for the rate of radical generation. 2) That free radical damage to mitochondrial function can be quantified by reciprocal plots of inverse slope giving the extrapolated Vm of mitochondria. 3) That a particular genetically deficient individual requiring high dosages of menadione has survived over 9 years. 4) That mitochondrial deficiency leads to an exercise hyperoxia.

Determinants of oxygen tension in normal and tumour tissues: A theoretical study

The partial pressure of O2 (pO2) at any point within the tissue surrounding a blood capillary is obtained through a modified version of the Erlang-Krogh model, in which the details of the intracapillary pressure profile and the axial diffusion of oxygen have been taken into consideration. The model is analytically solvable and contains only a single free parameter. A search for the major determinants of tissue O2 tension reveals that the parameters influencing the pO2 profile within the capillaries are the most sensitive factors. Experimentally obtained pO2 histograms of various normal and tumour tissues can be reproduced fairly accurately from the model.

Perivascular and tissue PO2 in contracting rat spinotrapezius muscle.

This study evaluated the possibility that during skeletal muscle contractions tissue O2 tension (Po2) around arterioles and venules decreases substantially more than in the middle of the capillary bed and thereby influences functional hyperemia. Periarteriolar [H+] and [K+] were also measured because most large arterioles are in close proximity to venules such that the biochemical status of the periarteriolar tissue could be influenced by a large decrease in O2 availability in the annulet of tissue surrounding the venules. Stimulation frequencies in the range of 2-12 Hz were used to activate the rat spinotrapezius muscle. Periarteriolar and capillary bed Po2, [H+], and [K+] changed during the first few minutes of stimulation but were restored to near resting concentrations as the functional hyperemia developed. However, perivenular Po2 decreased rapidly to approximately 50-60% of the resting gas tension as contractions began, and only minor recovery occurred. Elevation of tissue and periarteriolar Po2 with an O2-enriched superfusion solution did not prevent dilation during contractions to the same diameter as during the response at very low superfusion Po2. Therefore, the extent to which O2 influences arteriolar dilation and exercise hyperemia in the spinotrapezius muscle of the rat may depend less on periarteriolar and capillary bed Po2 than on the release of vasoactive materials from the nearby perivenular tissues as the availability of O2 decreases.

A microcomputer program of pulmonary and tissue gas exchange.

A microcomputer program written in BASIC for the IBM-PC and compatibles has been developed to analyze the effects of many parameters on the gas exchange and transport phenomena in the lungs and the tissues. The program is designed for use by medical students and residents concerned with gas exchange (anesthesiology, pulmonary diseases, critical care, etc.) to study the steady state effects on blood and tissue oxygen and carbon dioxide levels. The present program consists of two main subroutines: Pulmonary Gas Exchange and Tissue Gas Exchange. Steady state gas exchange at the lungs can be studied using either a three-compartment model or V/Q relationships. The V/Q subroutine uses single or multiple populations of V/Q distributions to determine gas exchange using a log-normal distribution of V/Q ratios. Other variables can be adjusted which determine the arterial and mixed-venous blood gases. These values are then fed into the second part of the program to analyze factors which determine tissue O2 tension. The Tissue Oxygen Tension subroutine is also subdivided into a modified Krogh-Erlang model, which provides a three-dimensional plot of theoretical capillary and tissue O2 tensions, and a Piiper model which includes the effect of diffusion shunt on O2 tensions and treats the tissue as a well-stirred compartment. Minimal and maximal tissue O2 tensions are calculated using the Piiper model since the intercapillary distance is allowed to vary depending on the O2 delivery by diffusion. Estimates of blood and tissue O2 tensions, diffusion/perfusion coefficients, amount of O2 delivered and the size of the active capillary bed are summarized in a table.

Pancreatic tissue oxygenation during secretory stimulation

Pancreatic acinar tissue O2 tension (PO2) was measured in anesthetized rats using recessed-tip microelectrodes (tip diam 1-2 micron). Pancreatic blood flow was measured using radioactive microspheres. Volume rate of pancreatic secretion, as well as protein concentration, was also measured. Average resting PO2 was 24.8 +/- 1.6 mmHg, with relatively little variation evident within a given pancreas. Bolus intravenous infusion of cholecystokinin octapeptide (CCK-OP, 4 micrograms X kg body wt-1) induced a reduction in tissue PO2 and profoundly increased protein output, while not directly affecting pancreatic blood flow. By contrast, secretin infusion (1.0 CU X kg body wt-1 iv bolus) affected neither tissue PO2 nor blood flow, although secretory rate increased by nearly sevenfold. This difference in PO2 response to the two compounds is interpreted in light of the fact that CCK-OP primarily stimulates acinar cell function, while secretin preferentially activates secretory epithelium. Pancreatic PO2 was found to be linearly related to resting blood flow at flows above 44 ml X min-1 X 100 g-1. No regional differences in blood flow were found in the head, body, and tail of the pancreas.

Effect of hemorrhagic shock on conjunctival and transcutaneous oxygen tensions in relation to hemodynamic and oxygen transport changes.

To evaluate possible physiologic mechanisms in hemorrhagic shock, sequential hemodynamics, O2 transport, conjunctival O2 (PcjO2), transcutaneous blood gases (PtcO2, PtcCO2), and core and conjunctival temperature (Tcore, Tcj) were measured during a control period, after hemorrhage, after reinfusion of the shed blood, and subsequently during terminal normovolemic shock in eight anesthetized dogs. The PtcO2 sensor requires surface heating to 44 degrees or 45 degrees C, whereas the PcjO2 sensor measures surface temperature but does not heat the tissue, thus avoiding heat-induced artifacts. Shortly after onset of hemorrhage, hemodynamic variables, bulk O2 transport, and tissue O2 tensions decreased abruptly. Prolongation of hemorrhage further deteriorated these variables. Reinfusion of the shed blood returned all values except PcjO2 to the normal range. In the terminal stage, all variables except PaO2 again deteriorated; decreased O2 transport impaired oxygen consumption, which in turn reduced both central and peripheral heat production. Lowered oxygen consumption, Tcore and Tcj reflect decreases in total-body and local tissue metabolism. These data are consistent with the concept that tissue O2 tension represents the balance between O2 supply and O2 demand and thus reflects overall O2 metabolism, which may be rate-limited by circulatory deficiencies.

Postoperative monitoring of myocardial oxygen tension: experience in 51 coronary artery bypass patients.

Following a preliminary feasibility report, polarographic monitoring of myocardial tissue O2 tension (Pmo2) in 51 coronary bypass patients has been accomplished. In this context, the influence of rapid atrial pacing (RAP), O2 inhalation, and intra-aortic balloon assistance (IAB) was statistically analyzed using Wilcoxon sign-rank and Student's t-tests. Electrodes were implanted in revascularized and nonrevascularized areas for comparison (24.0 +/- 1.1; and 26.3 +/- 1.8 mmHg Pmo2, p, not significant). Increasing myocardial O2 demand with RAP caused a 6% PmO2 drop (p less than 0.01). A 70% O2 inhalation increased Pmo2 by 30% (p less than 0.01). In 5 cases the benefit of IAB was confirmed by a 41% increase in Pmo2 (p = 0.02). These data support the clinical usefulness of polarographic Pmo2 as a measure of regional myocardial oxygenation. In addition to early recognition of intraoperative or postoperative graft failure previously reported, the efficacy of various therapeutic interventions can be more precisely determined.

Multiple mechanisms of reactive hyperemia in arterioles of the hamster cheek pouch.

To investigate mechanisms of reactive hyperemia, single arterioles of the hamster cheek pouch were occluded for periods of 1 s-3 min. Arteriolar diameters were measured upstream and downstream from the occlusion. O2 availability to the tissue was controlled by equilibrating the suffusate with low (0% O2) or high (10% O2) O2 gas mixtures. After very brief occlusions downstream sites dilated transiently, but upstream diameters did not change. Upstream and downstream diameters both increased during longer occlusions with O%-O2 and 10%-O2 suffusion. Microvascular pressure decreased at downstream sites and increased at upstream sites within 1-2 s of occlusion. During 0%-O2 suffusion tissue and periarteriolar O2 tensions (PO2's) began to decrease within 2 s of occlusion and had decreased halfway to their minimum value by 7 s. PO2's decreased only slightly during 10%-O2 suffusion. Calculated first-order rate constants for arteriolar diameter recovery decreased and total recovery time increased as occlusion duration was prolonged. This study suggests that multiple mechanisms (metabolic, myogenic, and passive) contribute to reactive hyperemia.

Effect of oxygen on arteriolar dimensions and blood flow in cat sartorius muscle.

The effect of O2 on arteriolar internal diameter, dual-slit velocity, and volume flow was studied by intravital microscopy in isolated autoperfused cat sartorius muscle. The muscle surface was covered with silicone oil, and gas mixtures containing 0, 5, 10, or 20% O2 in N2 were introduced over the muscle. When the O2 concentration was increased from 0 to 10%, arteriolar diameter, dual-slit velocity, and volume flow decreased on the average by 11 +/- 4, 30 +/- 29, and 37 +/- 13%, respectively. Under 20% O2, these parameters decrease by an additional 9 +/- 5, 29 +/- 10, and 30 +/- 14%, respectively. Percentage reduction in the diameter of large and small arterioles located at the same depth in the muscle were not significantly different. Conversely, the fall in volume flow was significantly greater in small arterioles. The lesser flow decrease in large vessels may reflect the fact that large vessels also feed deep muscle layers where the change in tissue O2 tension (PO2) is less. Our results do not support the hypothesis that small arterioles are intrinsically more sensitive to changes in tissue PO2.

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.

Lung as a model for evaluation of critical intracellular PO2 and PCO.

The relationship between cellular metabolism and tissue O2 tension was investigated using the isolated perfused rat lung. Lungs were ventilated with gas mixtures of varying PO2 under conditions of no net gas exchange so that alveolar and lung parenchymal gas tensions were in approximate equilibrium. When alveolar PO2 was reduced to 0.7 mmHg, there were significant increases in lung lactate production and perfusate lactate/pyruvate, and decreases in lung tissue ATP content and ATP/ADP. Metabolic parameters were unchanged by alveolar hypoxia when alveolar PO2 was 7 mmHg or greater. Changes of complete anoxia required a PO2 less than 0.04 mmHg. To determine competition between O2 and CO in lung metabolism, alveolar O2 was maintained at 5% and CO was varied from 0 to 90%. Significant changes in production of lactate and pyruvate and tissue ATP content occurred with an alveolar CO of 75% (CO/O2 = 15) but not with CO concentrations of 50%, (CO/O2 = 10) or less. These results with an intact organ confirm previous data with subcellular systems showing a high affinity of the mitochondrial respiratory chain for O2, and indicate that the metabolic changes of hypoxia do not occur until intracellular PO2 approaches 1 mmHg or the CO/O2 exceeds 10.

Cerebral blood flow and oxygen consumption in the rat brain during extreme hypercarbia.

The effects of hypercapnia (PaCO2 80, 160 and 300 torr) on cerebral metabolic rate for oxygen (CMRO2) and blood flow (CBF) were evaluated in paralyzed, mechanically ventilated rats by use of a 133Xe modification of the Kety-Schmidt inert-gas technique. Hypercapnic rats (PaCO, 80 torr) maintained on N2O, 70 per cent, had a sixfold increase in CBF and a 25 per cent increase in CMRO2, which were not prevented by adrenalectomy or decreases in tissue O2 tensions to near-normal values. Further increases in arterial blood CO2 tensions were associated with decreases in CMRO2 to normal (PaCO2 160 torr) or subnormal values (PaCO2 300 torr). In the last situation there was only a threefold increase in CBF. In rats with PaCO2 about 80 torr that were given propranolol, 2.5 mgċkg-1, during N2O anesthesia, there was only a threefold increase in CBF, while CMRO2 decreased to below normocapnic control values. Rats with PaCO2 80 torr given sedative or anesthetic doses of diazepam (ventilated with O2, 30 per cent, in N2) also had decreased CMRO2 values and had a twofold increase in CBF. It is concluded that hypercapnia activates catecholaminergic neurons in the brain, and that this activation increases oxygen consumption. The increase in flow that occurs with hypercapnia is markedly influenced by activity in catecholaminergic neurons.

Correlation between ventilatory and cerebrovascular responses to inhalation of CO.

To study the determinants of carbon monoxide (CO) induced hyperpnea simultaneous measurements were made of carboxyhemoglobin level in arterial blood (HbCO), ventilation (VE), cerebral blood flow (CBF), O2 delivery to the brain (CBF X O2 content of arterial blood), O2 consumption of the brain (CMRO2), and O2 tension in cerebral venous blood (PVO2) during inhalation of 1% CO in 40% O2 by six unanesthetized goats. HbCO increased to 65% in 10 min; VE remained constant until a HbCO level of approximately 50% was reached and then increased abruptly; CBF increased progressively; O2 delivery to the brain and CMRO2 decreased somewhat with CO inhalation; these decreases reached statistical significance at a HbCO level of 30-40% whereupon the rate of decline with respect to HbCO level increased substantially; and PVO2 decreased progressively from an average of from 31 to 14.6 Torr and averaged 19.2 Torr when hyperpnea was manifest. When considered in the light of previous studies which indicate that CO-induced hyperpnea is not caused by stimulation of the carotid bodies, these data suggest that this phenomenon is related to brain hypoxia. Calculations of brain tissue O2 tension with the Krogh equation support this contention.

Alterations in the coronary circulation of man following ascent to 3,100 m altitude.

Alterations in coronary blood flow associated with adaptation to high altitude were examined. Three normal men native to low altitude were studied, first at sea level, and again after 10 days' sojourn at 3,100 m altitude. During rest at high altitude, a 32% decrease in coronary blood flow was largely offset by a 28% increase in coronary arterial O2 extraction to maintain myocardial O2 delivery. The increase in O2 extraction resulted mainly from a decrease in coronary sinus blood O2 content and saturation. However, coronary sinus O2 tension remained constant, implying a decrease in the affinity of hemoglobin for O2. These observations are consistent with the hypothesis that coronary blood flow is regulated to maintain constant myocardial tissue O2 tension (as reflected here by coronary sinus blood O2 tension). The absence of a decrease in coronary sinus O2 tension or a decrease in myocardial lactate extraction imply that myocardial hypoxia did not develop. Therefore, myocardial hypoxia is not the basis for the decrease in cardiac stroke volume at high altitude reported previously and also observed in the present study.

Thermoregulation during work in carbon monoxide poisoning.

AbstractA mild to moderate CO poisoning, blocking 25 to 33 % of the oxygen binding capacity of the blood, was used to produce a change in maximal oxygen intake (max VO2). Subjects working at the same work load (Vo2= 1.5 1/min) for 1 hour under normal conditions and during CO poisoning showed an increase in plateau level of deep body temperature (Te8) of 0.3–0.5° C. The plateau levels correlated with the relative loads (percentage of max Vo2) of the subjects but not with absolute work load and oxygen uptake. The CO‐poisoning may act 1) directly on the hypothalamic temperature center, the low tissue O2 tensions changing the activity of its neurons, 2) through the low venous O2 tensions on peripheral chemoreceptors in the working muscles or the venous side of the circulation, or 3) the changes in temperature may be a passive reaction to a shift in blood towards the periphery in the CO poisoned state.

Tensions of O2 and CO2 in gas pockets of germfree rats.

Tissue O2 and CO2 tensions were estimated with subcutaneous gas pockets in germfree rats, conventional rats, and germfree rats that were newly-infected with a normal rat intestional bacterium, Clostridium difficile. Differences between groups were not large. Newly-infected rats appeared to have low local blood flow the first day and an additional unexplained low pCO2 the second day after infection. Germfree female rats had lower pCO2 than germfree or conventional males and conventional females.

DETERMINATION OF TISSUE O2 TENSIONS BY HOLLOW VISCERAL TONOMETERS: EFFECT OF BREATHING ENRICHED O2 MIXTURES.

DETERMINATION OF TISSUE O2 TENSIONS BY HOLLOW VISCERAL TONOMETERS: EFFECT OF BREATHING ENRICHED O2 MIXTURES.

Action of sodium salicylate on tissue gas tensions.

SummaryIn the rat, sodium salicvlate in doses of 200 mg/kg/24 hr produced a fall in tissue CO2 and O2 tensions, effects due to the increased alveolar ventilation and relatively greater increase of tissue oxygen consumption than tissue perfusion.