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Increases in both buccal and sublingual partial pressure of carbon dioxide reflect decreases of tissue blood flows in a porcine model during hemorrhagic shock.

BACKGROUND: Earlier studies had demonstrated that gastric partial pressure of carbon dioxide (PCO2) of the gastric wall is an early indication of perfusion failure. Because hypercarbia is a general phenomenon of perfusion failure, this study investigated whether sublingual and buccal mucosal tissue PCO2 also serve as a sensitive indicator of systemic blood flow during hemorrhagic shock. METHODS AND RESULTS: Hemorrhagic shock was induced in five male domestic pigs. Buccal and sublingual PCO2 increased from 60 to 129 mm Hg (p < 0.01) in parallel with average decreases in cardiac output to 44% (from 6.1 to 2.8 L/minute; p < 0.01), and mean arterial pressure to 47% (from 115 to 57 mm Hg; p < 0.01), over the 2-hour interval of shock. According to colored microspheres used for measurements, buccal mucosal flow decreased to 35% (from 6.3 to 2.2 mL/minute/100 g; p < 0.01) in close parallel with sublingual blood flow, which decreased to 34% (from 7.2 to 2.5 mL/minute/100 g; p < 0.01). Liver flow decreased to 56% (from 152 to 85 mL/minute/100 g;p < 0.01), and renal flow to 47% (from 272 to 128 mL/minute/100 g;p < 0.01) of baseline values. The procedure yielded to overall comparable volume exchanges in different animals. After reinfusion of shed blood, buccal PCO2, like sublingual PCO2, was restored to approximately baseline values (respectively, from 56 to 71 mm Hg and from 60 to 71 mm Hg; p = not significant), together with arterial pressure, cardiac output, and end-tidal CO2 (EtCO2) (respectively, from 115 to 115 mm Hg, from 6.1 to 6.3 L/minute, and from 35 to 39 mm Hg; p = not significant), but there was delayed reversal of lactic acidosis (from 0.7 to 2.5 mmol/L;p < 0.01). In five unbled control animals, no significant changes were observed over the same interval. CONCLUSION: The current study extends the rationale for noninvasive measurements to both buccal and sublingual mucosa for diagnosis and quantitation of hemorrhagic shock severity.

Animals↗

Low toxicity of nitric oxide against endothelial cells under physiological oxygen partial pressures.

Cultured rat liver endothelial cells were incubated with 1 and 2 mM spermineNONOate at different O2 concentrations in the incubation atmosphere. (Z)-1-{N-[3-Aminopropyl]-N-[4-(3-aminopropylammonio) butyl]-amino}diazen-1-ium-1,2- diolate (spermineNONOate), at 2 mM, was highly cytotoxic at 21% and 95% O2 (as measured by lactate dehydrogenase release); more than 80% of the cells were damaged after 6 h of incubation. Cytotoxicity induced by 2 mM spermineNONOate was significantly decreased at 10%, 5% and 0% O2; cell death was 54%, 36% and 25% respectively after 6 h of incubation. In contrast, 1 mM spermineNONOate was almost non-toxic towards the cells. Only at 95% O2 was a slight damaging effect, of 25%, observed. The nitric oxide (.NO) concentrations released from 1 and 2 mM spermineNONOate were determined as varying between 5 and 12 microM and between 12 and 22 microM respectively as measured by the oxyhaemoglobin and the NO cheletropic spin-trapping methods. The decomposition rate of spermineNONOate and the resulting .NO concentrations were independent of O2 at all applied concentrations. Likewise, the steady-state concentrations of H2O2 remained at approx. 1 nM at all O2 concentrations, as measured with the fluorescent dye scopoletin. L-Tyrosine and L-ascorbate, both of which are known to scavenge reactive nitrogen species, markedly diminished spermineNONOate-induced cytotoxicity at 95% O2. The formation of 3-nitrotyrosine, indicating the reaction of L-tyrosine with nitrogen dioxide (.NO2) and/or peroxynitrite anions, was enhanced in incubations with spermineNONOate at 21% and 95% O2. The results demonstrate that at O2 partial pressures typically found under physiological conditions and at .NO concentrations that can occur in vivo, .NO alone is almost non-toxic towards cultured rat liver endothelial cells. .NO at these concentrations in vivo, however, exerts toxic effects at supraphysiological O2 partial pressures, owing to its oxidation to reactive nitrogen species such as .NO2.

Animals↗

[Transcutaneously measured carbon dioxide partial pressure in non-hypoxic fetuses during labor].

Using the newly developed Severinghaus electrode we performed measurements of the transcutaneous carbon dioxide partial pressure (tcPco2) in 81 non-hypoxic fetuses during labor. The calibration and measuring temperature was 39 degrees C. After a correction with a factor of 13% the transcutaneous Pco2 values corresponded well with the blood values of the Pco2 from FBA respectively the umbilical artery. While during the first stage of labor we found only a gradual rise in the tcPco2 level, we observed a rapid rise at the end of the second stage. Analysing the influence of clinical factors on the fetal tcPco2 level we found statistically significant higher levels during the first stage of labor in primipara compared with multipara. However there was no significant difference dependent on gestational age, the age of the mother and the birthweight.

Birth Weight↗

A computer-supported oxystat system maintaining steady-state O2 partial pressures and simultaneously monitoring O2 uptake in biological systems.

A feedback-controlled oxystat system is described maintaining steady-state O2 partial pressures (pO2) between 0.01 mmHg (14 nM-O2) and 150 mmHg (210 microM-O2) and simultaneously monitoring O2 uptake at rates between 0.1 and 120 microM-O2 X min-1 in suspensions of cells, in subcellular fractions and in solutions of enzymes. At pO2 values between 0.2 and 150 mmHg (0.28 and 210 microM-O2) a polarographic O2 sensor was used, and below a pO2 of 0.2 mmHg (0.28 microM-O2) the O2-dependent luminescence of the photobacterium Vibrio fischeri was utilized to monitor the actual pO2. At a selected pO2, O2 supply is maintained by injecting appropriate amounts of O2-saturated aqueous medium into the reaction chamber by using a motor-driven burette. The oxystat system is under control of a computer that reads the O2 sensors, interacts with the motor-driven burette, calculates the O2 uptake from the amounts of O2-saturated medium added, collects data from further measuring devices and provides the documentation of the results during incubation.

Computers↗

Nitrogen partial pressures in man after decompression from simulated scuba dives at rest and during exercise.

In 5 subjects arterial and central venous nitrogen partial pressures (PN2) were measured after decompression from a chamber dive following a decompression schedule for scuba diving. The simulated dives consisted of exposure to air at 6 bar for 30 min corresponding to a depth of 50 m. Afterward the subjects were decompressed with decompression stops at 2.5, 2.2, 1.9, 1.6, and 1.3 bar with a total decompression time of 67 min. In 3 of the subjects the measurements were repeated after they had exercised (workload 75 W) during bottom time. Immediately after decompression and every 40 min until Minute 240 arterial and central venous blood samples were analyzed for PN2 using a manometric Van Slyke apparatus. Venous PN2 remained elevated until 160 min after decompression, indicating still incomplete nitrogen washout for at least 2 h after decompression had been accomplished. We did not find any difference in PN2 values after decompression from dives at rest and after exercise. Applying a computer program based on a wide range of theoretical tissue half-times nitrogen elimination proved to be consistent with Haldanian theories when using our decompression profile. Our data confirm that nitrogen elimination is prolonged after decompression from simulated dives at rest and after exercise.

Adult↗

Lipid peroxidation and cell viability in isolated hepatocytes in a redesigned oxystat system: evaluation of the hypothesis that lipid peroxidation, preferentially induced at low oxygen partial pressures, is decisive for CCl4 liver cell injury.

An oxystat system is described which is capable of maintaining steady-state oxygen partial pressures (PO2) at levels between 0.1 and 300 mm Hg for hours or even days in incubations of respiring cells. The system was used to study effects of the hepatotoxin carbon tetrachloride (CCl4) on lipid peroxidation and cell viability in isolated hepatocytes from phenobarbital-pretreated rats at various steady-state PO2. At PO2 below 35 mm Hg, with a maximum effect at 7 mm Hg, CCl4 induced an immediate lipid peroxidation, the rate of which slowed down during further incubation. AT PO2 between 35 and 70 mm Hg, CCl4 initially induced only slight lipid peroxidation, while there was a significant increase in lipid peroxidation after approximately 30 min. At PO2 above 100 mm Hg, no lipid peroxidation was induced by CCl4. At PO2 of 70 mm Hg and below, with the maximum effect at 3 mm Hg, CCl4 also induced marked losses of cell viability. Under anaerobic conditions and at PO2 greater than 70 mm Hg, CCl4 was without effect on the viability of the liver cells. Cells isolated from the pericentral area of the liver lobule showed more lipid peroxidation and loss of cell viability than cells from the periportal area of the lobule. These results provide further evidence for the decisive role of lipid peroxidation, preferentially induced at low PO2, in CCl4 liver injury.

Animals↗

Skeletal muscle partial pressure of oxygen in patients with sepsis.

OBJECTIVE: In order to obtain direct evidence for tissue hypoxia in patients with sepsis oxygen, partial pressure was measured within skeletal muscle. Furthermore, serial intermittent and continuous measurements of skeletal muscle PO2 in patients with sepsis were used to find out whether skeletal muscle oxygenation may change in the course of sepsis and depends on the severity of sepsis. DESIGN: Prospective study. SETTING: Intensive care unit of a university hospital. PATIENTS: Intensive care patients (n = 98) with sepsis (group 1, n = 39; group 4, n = 28), limited infection (group 2, n = 16), and cardiogenic shock (group 3, n = 15). INTERVENTIONS: Pulmonary artery catheterization; standard antibiotic therapy and volume replacement. MEASUREMENTS AND MAIN RESULTS: Skeletal muscle PO2 was determined by polarographic needle electrodes or catheter probes. In patients with sepsis (n = 67), no evidence for skeletal muscle hypoxia was obtained from the PO2 distribution within biceps muscle. Mean skeletal muscle PO2 was increased in patients with sepsis (group 1, 48 torr [6.4 kPa]) compared with patients with limited infection (group 2, 28 torr [3.7 kPa]), p < .001) and with patients with cardiogenic shock (group 3, 22 torr [2.9 kPa], p < .001). Serial measurements of the PO2 distribution during seven consecutive days in another 28 patients (group 4) with sepsis showed that a more severe degree of sepsis was associated with an increase of mean skeletal muscle (p < .001). These results were confirmed by continuous measurements of mean skeletal muscle PO2, using PO2 catheters. CONCLUSIONS: In patients with sepsis, oxygen transport to skeletal muscle was not critically reduced. Serial intermittent and continuous measurements of skeletal muscle PO2 showed that skeletal muscle PO2 increased in relation to the severity of the stage of sepsis. Our findings suggest that oxygen utilization within skeletal muscle decreased with deterioration of sepsis, thereby increasing skeletal muscle PO2.

Adult↗

[Continuous monitoring of spontaneous respiration in the postoperative phase. 4. The effect of postoperative pain therapy on cutaneous oxygen and carbon dioxide partial pressure following gynecologic surgery with neuroleptanalgesia].

METHODS: Cutaneous O2 and CO2 pressures were monitored for 16 h in 55 female patients recovering from major gynaecological surgery performed under neurolept anaesthesia. Postoperative pain was managed either with an antipyretic analgesic (i.m. or i.v. metamizol up to 2.5 g/4 h; group NLA) or with i.v. patient-controlled analgesia using fentanyl (demand dose 34 micrograms, infusion rate 4 micrograms/h, hourly maximum dose 0.25 mg, lock-out time 1 min; group NLA/PCA). In addition, 11 patients received a single i.v. bolus injection of 150 mg amiphenazole, a respiratory stimulant, at the beginning of PCA treatment (group NLA/PCA/AMI). Data were collected and stored by a personal computer, using the TCM3 system with a combination electrode for simultaneous measurement of cutaneous oxygen and carbon dioxide partial pressures (TINA, Radiometer) at 30-s intervals. The overall observation period was four times 240 min; patients from the NLA group who required additional opioids were excluded from the analysis. Means and standard deviations were calculated for individual data and data pooled for 15- or 60-min intervals. Groups were compared by means of the chi-square test, Student's t-test or analysis of variance (level of significance, P < or = 0.05). RESULTS: The 55 patients were classified as ASA I-II. The study groups were comparable with respect to demographic and anaesthesiological data, except that those in the NLA group were younger and had received less intraoperative fentanyl (Table 1). Mean PCA fentanyl consumption was 0.6-0.7 mg in the 16-h observation period (Table 2). In all groups, pctO2 levels were decreased and pctCO2 levels elevated in the first observation hours and slowly returned to normal within the first observation period (Figs. 1, 2, Tables 3, 4). Episodes of hypercapnia (pct-CO2 > 50 or > 55 mm Hg) were frequent in the first 2 h (8-29% of individual values for pctCO2 > 50, up to 5% of values recorded for pctCO2 > 55; Table 4). There were no statistically significant differences between patients treated with metamizol and those treated with fentanyl. Amiphenazole did not significantly improve postoperative respiration. PCA patients had occasional episodes of hypercapnia (up to 19% of all values for pctCO2 > 50, up to 5% for pctCO2 > 55) even in the last observation period (13-16 h after surgery), indicating the need for close monitoring of spontaneous ventilation during PCA following neurolept anaesthesia. DISCUSSION AND CONCLUSIONS: The present study confirmed that spontaneous respiration in the early postoperative period can be monitored non-invasively by measuring cutaneous partial pressures of carbon dioxide and, less precisely owing to wide individual variations, oxygen. It showed that spontaneous respiration is less effective immediately after termination of surgery under neurolept anaesthesia and recovers slowly over the next 4 h. During the first observation period, ventilation was no worse with i.v. PCA using fentanyl than with conventional pain management using the antipyretic analgesic metamizol, confirming the hypothesis that opioid-induced respiratory depression occurs only at overdosage (which is not a problem with individualized dose titration using PCA). Since all patients in the NLA group required additional opioids after the first observation period and had to be excluded from further analysis, it cannot be decided from the present data whether late hypercapnia was due to PCA or to residual effects of surgery and anaesthesia. The respiratory stimulant amiphenazole (150 mg i.v.) was not helpful in improving ventilation; there was no indication of analgesic effects or interactions of amiphenazole.

Adult↗

The temperature, pH, and partial pressure of oxygen in the cervix and uterus of women and uterus of rats during the cycle.

Changes in the temperature, pH, and partial pressure of oxygen (PO2) in the cervical canal and cavum uteri were measured in women with or without an intrauterine device and in the uteri of rats throughout the cycle. Only the PO2 exhibited significant variations, rising during the ovulatory phase in both cervices of women and uteri in rats. It is speculated that the rise in PO2 is related to the function of these organs as reservoirs for spermatozoa.

Adult↗

Relations between pH, oxygen partial pressure and growth in cultured cell spheroids.

The pH gradients, oxygen partial-pressure gradients and growth curves were measured for 7 different types of spheroids. Growth curves were measured in liquid overlay culture and thereafter the spheroids were attached to cover glasses and transferred to a chamber for micro-electrode measurements. The spheroids were randomly divided for pH or pO2 measurements which then were made under conditions as identical as possible. The decreases in pO2 and pH, delta pO2 and delta pH were calculated as the difference between the values in the culture medium and the values 200 micron inside the spheroids. Each type of spheroid had a certain relation between delta pO2 and delta pH. The human colon carcinoma HT29, the mouse mammary carcinoma EMT6 and the hamster lung V79-379A spheroids had high values of the quotient delta pO2/delta pH. The human thyroid carcinoma HTh7 spheroids and the 3 types of human glioma spheroids had lower quotients. There was a tendency for fast-growing spheroids to have high quotients. Two extreme types of spheroids, HT29 (high quotient) and U-118 MG (low quotient) were analyzed for lactate production and oxygen consumption. The U-118 MG spheroids produced about 3 times more lactate and consumed about 3 times less oxygen than the HT29 spheroids. The differences in lactate production could not be explained by differences in the pyruvate Km values of lactate dehydrogenase. The results indicate that there are significant metabolic differences between the spheroid systems studied.

Animals↗

Clinical experience with 118 brain tissue oxygen partial pressure catheter probes.

OBJECTIVE: We assessed the technical and diagnostic reliability of partial pressure of oxygen (PO2) of brain tissue (P(ti)O2) monitoring. The monitoring system and the catheter probes were tested in vitro, and clinical experiences obtained with 118 brain P(ti)O2 catheter probes, used in 101 patients, are reported. METHODS: The polarographic (LICOX; Medical Systems Corp., Greenvale, NY) P(ti)O2 catheter probe lies 22 to 27 mm below the dura level; its PO2-sensitive surface is 7.1 mm2. For 10 patients, the adaptation time (with initially unreliable signals after insertion) was determined. For 27 patients, the probe was removed in a stepwise fashion (three increments of 5 mm) and the heterogeneity of brain P(ti)O2 levels was investigated. After removal of the catheter probes, their PO2 and zero display error values were determined and compared with probe performance data obtained in vitro with unused PO2 catheter probes. RESULTS: Small iatrogenic hematomas were observed for two patients (1.7%). No infection occurred after 6.7 +/- 3.9 days (mean +/- standard deviation) of monitoring. The technical complication (dislocation or defect) rate was 13.6%. The mean adaptation time was 79.0 +/- 51.7 min. A flow chart is presented, which helps to rule out artifacts. The mean P(ti)O2 measured at 22 to 27 mm below the dura was 23.8 +/- 8.1 mm Hg, at 17 to 22 mm was 25.7 +/- 8.3 mm Hg, at 12 to 17 mm was 33.0 +/- 13.3 mm Hg (P < 0.01, compared with the initial value), and at 7 to 12 mm was 33.3 +/- 13.3 mm Hg (P < 0.01). Recent catheter probe versions exhibited a PO2 display error of -1.2 +/- 5.1% (mean +/- standard deviation, n = 38) and a mean zero display error of 1.1 +/- 0.9 mm Hg (n = 34). The greatest PO2 display errors were measured during the first 4 days of continuous monitoring. In the in vitro test (of 12 unused catheter probes), the maximal probe display error was 1.07 +/- 2.14%, tested at temperatures between 22 degrees C and 37 degrees C and tested at oxygen pressures of 0, 44, and 150 mm Hg. In vitro, the zero display error was -0.21 +/- 0.25 mm Hg. CONCLUSION: Brain P(ti)O2 monitoring, reflecting an area 17 to 27 mm below the dura, is a safe and reliable technique for monitoring cerebral oxygenation. Excluding the first 1 hour after insertion, data are reliable, with almost 100% good data quality.

Artifacts↗

Soybean seed growth in response to long-term exposures to differing oxygen partial pressures.

Short-term studies have indicated that alterations in the oxygen partial pressure (pO(2)) around developing soybean (Glycine max [L.] Merr.) seeds may alter seed growth characteristics. A 2-year field study was undertaken to determine the effects on seed development of long-term exposures of individual pods to either sub-ambient or supra-ambient pO(2). Pod chambers were used through which fixed pO(2) were continuously flowed throughout seed development. No effects on maturity date were observed from exposures to either sub-ambient or supra-ambient pO(2). On the other hand, seed weight was reduced by 0.10 pO(2) in both years of the study implicating an O(2) limitation on seed growth rate at this fairly high pO(2). In 1 of the 2 years, supra-ambient pO(2) resulted in increased seed weight.

Journal Article↗

[Development of a method of continuous monitoring of spontaneous respiration in the postoperative phase. 1. Normal values for cutaneous pO2- and pCO2-partial pressure together with pulse oximetry determined oxygen saturation in healthy young volunteers].

METHODS: Twenty-eight healthy volunteers of both sexes (14 male, 14 female, age 31 +/- 7 years, weight 70 +/- 12 kg) breathing room air were monitored for cutaneous partial pressures of oxygen and carbon dioxide (pctO2, pctCO2) and partial oxygen saturation (psO2) as determined by pulse oximetry. Data triplets were collected and stored by a personal computer at 30-s intervals during a 4-h resting period to establish a confidence range for the devices in use (TCM 3 with a combination electrode E 5270, and Pulse Oximeter, Radiometer). This data range was intended to be used in later noninvasive, continuous respiratory studies with postoperative patients. Means, standard deviations, and ranges were calculated for individual data and data pooled from 15-min intervals. Data distribution over time was calculated for 30-min intervals. RESULTS: Contrary to the saturation data delivered by pulse oximetry, the pctO2 and pctCO2 readings needed about 15 min to stabilize. The mean +/- SD of a total of 12,600 pctO2 measurements (77.2 +/- 10.9 mmHg) could not simply be compared with arterial normal values, whereas the pctCO2 measurements (39.9 +/- 3.6 mmHg) fit well with arterial data from the literature. Interestingly, pctCO2 values in unmedicated healthy adults were not uniformly distributed, suggesting individual differences in either skin permeability of central regulation of respiration. Additionally, the pctO2 readings were characterized by serious inter-subject variability, which confirms earlier studies that pctO2 is not suitable for routine monitoring procedures in adults, the mean +/- SD of a total of 4500 psO2 measurements was 94.9 +/- 1.6%. A statistically significant correlation was found between pctO2 and psO2 (r = 0.358). Cutaneous carbon dioxide readings of greater than 50 mmHg were observed in only 0.06% of all 12,600 data sets (maximum 51.3 mmHg; 28 volunteers), desaturations (less than 90%) in only 0.24% of all 4,500 saturation measurements (minimum 86%; 10 volunteers). DISCUSSION AND CONCLUSION: Monitoring of spontaneous respiration in the recovery room is regarded as essential to prevent serious complications resulting from surgery and anesthesia. This has become particularly true with newer analgesic techniques like spinal opiates or patient-controlled analgesia. Since minor degrees of opiate-induced respiratory depression are easily influenced by external stimulation, it is mandatory that any monitoring of spontaneous respiration must be nonstimulant, and prefereably noninvasive. The present communication is the first of a series of investigations to develop of monitoring technique for postoperative patients. Because normal values for the parameters studied are either lacking or dependent on the monitoring devices in use, the present paper defined the respective data ranges. It is concluded that pulse oximetry and pctCO2 measurement are both useful and sensitive for continuous, non-invasive respiratory monitoring in adults, whereas pctO2 measurements are of lesser value. Results in volunteers treated with opiates and postoperative patients under patient-controlled analgesia using the above mentioned equipment will be reported in following publications.

Adult↗

Antioxidant reactions of all-trans retinol in phospholipid bilayers: effect of oxygen partial pressure, radical fluxes, and retinol concentration.

Lipoperoxyl radical-scavenging activity of retinol in unilamellar soybean phosphatidylcholine liposomes was studied under a variety of conditions to appreciate to what extend retinol may be considered an effective antioxidant. Peroxidation, initiated by 2 mM 2,2'-azobis(amidino-propane)hydrochloride (AAPH), was carried out at 160 torr O2 or at 15 torr O2, in the absence or in the presence of 10 to 40 mM retinol. As evaluated by the length of the inhibition periods, t(inh), and by the ratio between the inhibition and propagation rate, R(inh)/R(p), the antioxidant activity of retinol was higher at 15 torr O2 than at 160 torr O2. The consumption rate of retinol was markedly faster at 160 torr O2 than at 15 torr O2 and increased with the increase of retinol concentration under both oxygen tensions. When liposome peroxidation was carried out under N2, retinol consumption was independent of retinol concentration. Peroxyl radicals oxidize retinol to 5,6-retinol epoxide. The ratio between 5,6-epoxide formed and the retinol consumed was markedly higher at 15 torr O2 than under air and decreased with the increased retinol concentrations. When butylated hydroxytoluene was included into the liposomal suspension, most of the consumed retinol was converted into 5,6-epoxide. Liposomes were incubated at 15 torr O2, in the presence of 0.5 to 10 mM AAPH. The antioxidant effectiveness of 40 mM retinol, as measured by the R(inh)/R(p) ratio, increased with the increase of the radical fluxes. The results suggest, besides radical trapping, that a major consumption of retinol during lipid oxidation occurs through self-oxidation reactions, which are concentration- and oxygen-dependent. A decreased self-oxidation makes retinol a better lipoperoxyl radical scavenger at low, rather than at high partial pressure of oxygen. However, when self-oxidation of retinol is prevented, only a minor fraction of the antioxidant is allowed to effectively act as a radical scavenger, suggesting that the radical-trapping reactions are rate-limiting for the antioxidant process. Peroxyl radical concentration, by shifting the route of the retinol activity toward radical scavenging, brings about an increasingly more efficient radical trapping. It is concluded that all-trans retinol behaves as a more effective antioxidant at low oxygen partial pressure, low retinol concentrations, and high radical flux.

Antioxidants↗

A mathematical model of the hemoglobin-oxygen dissociation curve of human blood and of the oxygen partial pressure as a function of temperature.

A mathematical model is described giving the oxygen saturation fraction (s) as a function of the oxygen partial pressure (p): y - y0 = x - x0 + h X tanh [k X (x - x0)], where y = kn[s/(1-s)] and x = ln(p/kPa). The parameters are: y0 = 1.875; x0 = 1.946 + a + b; h = 3.5 + a; k = 0.5343; b = 0.055 X [T/(K - 310.15)]; a = 1.04 X (7.4 - pH) + 0.005 X Cbase/(mmol/L) + 0.07 X [[CDPG/(mmol/L)] - 5], where Cbase is the base excess of the blood and CDPG is the concentration of 2,3-diphosphoglycerate in the erythrocytes. The Hill slope, n = dy/dx, is given by n = 1 + h X k X [1 - tanh2[k X (x - x0)]]. n attains a maximum of 2.87 for x = x0, and n----1 for x----+/- infinity. The model gives a very good fit to the Severinghaus standard oxygen dissociation curve and the parameters may easily be fitted to other oxygen dissociation curves as well. Applications of the model are described including the solution of the inverse function (p as a function of s) by a Newton-Raphson iteration method. The po2-temperature coefficient is given by dlnp/dT = [A X alpha X p + CHb X n X S X (1 - s) X B]/[alpha X p + CHB X n X s X (1 - s)], where A = -dln alpha/dT approximately equal to 0.012 K-1; B = (lnp/T)s = 0.073 K-1 for y = y0; alpha = the solubility coefficient of O2 in blood = 0.0105 mmol X L-1 X kPa-1 at 37 degrees C; CHb = concentration of hemoglobin iron in the blood. Approximate equations currently in use do not take the variations of the po2-temperature coefficient with p50 and CHb into account.

Chemical Phenomena↗

Pharmacological modifications of the partial pressure of oxygen in murine tumors: evaluation using in vivo EPR oximetry.

EPR oximetry using an implantable paramagnetic probe was used to quantify the partial pressure of oxygen (pO(2)) in tissues in a transplantable mouse tumor model (TLT) after administration of 34 different vasodilators belonging to one of the following classes: angiotensin-converting enzyme inhibitors, calcium antagonists, alpha antagonists, potassium channel openers, beta-blockers, NO donors, and peripheral vasoactive agents. Twenty-four compounds were efficient in significantly increasing the local pO(2) in a majority of tumors. The increase of local pO(2) using pharmacological treatments was lower than that achieved by using oxygen or carbogen breathing. This technique offers an unprecedented tool for rapidly and accurately measuring treatment-induced modifications of pO(2) in tumors. Magn Reson Med 42:627-630, 1999.

Animals↗

Critical capillary oxygen partial pressure and lactate threshold in patients with cardiovascular disease.

OBJECTIVES: The aim of this study was to determine the relation between femoral vein oxygen partial pressure (PO2) and lactate increase during exercise in patients with cardiovascular disease. BACKGROUND: Considerable controversy surrounds the relation between the increase in lactate during exercise and the oxygen supply to the exercising muscles. We assumed that femoral vein PO2 would be a measure of end-capillary PO2 during leg-cycling exercise and that it would decrease to a "floor" level when the critical capillary PO2 (the PO2 below which the capillary-mitochondrial difference would be too low to allow oxygen consumption) was reached. At the critical capillary PO2, anaerobic metabolism should take place, and lactate should increase in the effluent blood. METHODS: Ten patients with cardiovascular disease performed two 6-min constant work rate tests (moderate and heavy intensity) and an incremental exercise test to the symptom-limited maximum on a cycle ergometer. Femoral vein blood was repeatedly sampled through a percutaneous catheter before and during each exercise test. RESULTS: The PO2 rapidly decreased toward a minimal value with increasing oxygen uptake for all three tests in all patients. After reaching its nadir (18.2 +/- 2.0 mm Hg), the PO2 remained unchanged in five patients but increased in the other five patients despite the further increase in work rate and oxygen uptake. The relation between PO2 and oxygen uptake was characteristic for each patient and independent of the protocol used for the study. Femoral vein lactate did not change appreciably until PO2 reached the minimal (critical) value. Thereafter, it dramatically increased without a further decrease in PO2. The minimal PO2 was positively correlated with the peak oxygen uptake (r = 0.70, p = 0.01). CONCLUSIONS: During leg-cycling exercise, muscle capillary PO2 reaches a minimal value in the midrange of the subjects' work capacity before lactate concentration increases in patients with cardiovascular disease. The lack of further decrease in PO2 at the oxygen uptake at which lactate starts to increase suggests that the minimal capillary PO2 is the "critical" capillary PO2.

Aged↗