Median pO2 Research Articles

Intratumoral pO 2 predicts survival in advanced cancer of the uterine cervix

Experimental evidence suggests that the hypoxic fraction in a solid tumor may increase its malignant potential and reduce its sensitivity towards non-surgical treatment modalities (e.g. standard irradiation, certain anticancer agents). However, the clinical importance of tumor hypoxia remains uncertain since valid methods for the routine measurement of intratumoral O 2-tensions in patients have so far been lacking. A clinically applicable standardized procedure has been established which enables the determination of intratumoral oxygen tensions in advanced cervical cancers by use of a computerized polarographic needle electrode histography system. Tumor oxygenation as measured by this method represents a novel tumor feature which can be individually determined for each tumor and which is independent from other known oncological parameters. The results of an interim analysis of an open prospective clinical trial to evaluate the prognostic significance of tumor oxygenation based on the survival data of the first 31 patients are presented. Fifteen patients have been treated by primary radiation, 11 patients received multimodality therapy including irradiation. After a median follow-up of 19 months (range 5–31 months), Kaplan-Meier-life table analysis showed significantly lower survival and recurrence-free survival for patients with a median p02 of ≤10 mm Hg compared to those with better oxygenated tumors (median pO 2> 10 mmHg). The Cox proportional hazards model revealed that the median pO 2 and the clinical stage according to the FIGO are independent, highly significant predictors of survival and recurrence-free survival. We conclude from these preliminary results that tumor oxygenation as determined with this standardized procedure appears to be a new independent prognostic factor influencing survival in advanced cancer of the uterine cervix.

Oxygen tension measurements in human tumors: The institut gustave‐roussy experience

AbstractTumor hypoxia contributes to the response to radiotherapy and to chemotherapy. The oxygenation status of normal tissues and tumors was evaluated using the KIMOC‐6650 histograph in 35 patients with head and neck tumors, 13 patients with metastatic malignant melanoma (MMM), and 6 patients with uterine cervical carcinoma. Patient compliance was good. The pO2 values measured in tumors were in general lower than those measured in normal tissues of the same patient. The pO2 in the tumors varied along the track and from one track to another. Important pO2 variability was also detected from one tumor to another. Patients with head and neck tumors had a median pO2 of 6.76 kPa (52 mmHg) in normal tissues (subcutaneous) and 1.33 kPa (10 mmHg) in tumors with 25% of the values below 0.26 kPa (2 mmHg). Patients with MMM had a median pO2 of 3.64 kPa (28 mmHg) in normal tissues (subcutaneous tissues and muscles) and pO2 was 0.91 kPa (7 mmHg) in tumors with 18% of the values below 0.26 kPa. Patients with uterine cervical carcinoma had a median pO2 of 6.37 kPa (49 mmHg) in normal tissues (vagina) and 2.73 kPa (21 mmHg) in tumors with 16% of the values below 0.26 kPa. The data for N2 and N3 head and neck nodes showed significantly more values below 0.26 kPa (2 mmHg) as nodal size increased (P < 0.001 by chi‐square test). The best parameters to describe tissue oxygenation are discussed. © 1994 Wiley‐Liss, Inc.

Vaginal Po 2 in healthy women and in women infected with Trichomonas vaginalis: Potential implications for metronidazole therapy

We measured the PO2, pH, and temperature in the vaginal canals of nine patients with symptomatic Trichomonas vaginitis and those of 10 healthy women. The patients included eight women with primary infections caused by metronidazole-susceptible strains and one refractory case that resulted from infection with a metronidazole-resistant Trichomonas vaginalis. The median vaginal PO2, pH, and temperature in the patient group were 1 mm Hg, 6, and 37.3 degrees C respectively; these medians were 1 mm Hg, less than or equal to 4.5, and 37.2 degrees C in the healthy group. These data show that vaginal environment is anaerobic or microaerophilic (it has reduced oxygen tension). Because the activity of metronidazole is reduced under aerobiosis, the vaginal environment should enhance the biologic activity of the drug.

Combined tissue oxygen tension measurement and positron emission tomography studies on glucose utilization in oncogene-transformed cell line tumour xenografts in nude mice

Glucose utilization studies using high resolution positron emission tomography and tissue oxygenation measurements using microelectrode techniques were carried out in nude mice bearing oncogene-transformed (Rat1pEJ6.6 and REFpneoMYCrasEpool) cell line tumours and a non-transformed (Rat1) cell line tumour to determine the correlation between glucose utilization, tissue oxygenation and tumour growth rate. Control measurements were performed in the subcutis of tumour-free animals. Accelerated growth rates were observed in both ras-transformed cell lines with tumour doubling times of 2.5-4 days while Rat1 tumours had a doubling time of 28 days. Since rapid growth rates necessitate elevated consumption of oxygen and nutrients, severe tumour hypoxia was observed in tumours from both ras-transformed cell lines; median pO2 being 1-5 mmHg (tumour sizes ca. 400 mm3). Size-matched Rat1 tumours exhibited a median pO2 value of 12 mmHg corresponding to the slow growth rate. Comparing both ras-transformed cell lines, Rat1pEJ6.6 tumours had a more adequate vascularization than REFpneoMYCrasEpool tumours indicated by a better tissue oxygenation (5 mmHg versus 1 mmHg) and higher glucose metabolic rates (13.4 +/- 2.2 mumol/min/100 cm3 versus 9.7 +/- 1.3 mumol/min/100 cm3). At advanced growth stages, a reduction of tissue oxygen levels is obtained which is accompanied by a 30% elevation of glucose metabolic rate. The data presented here demonstrate for the first time an impact of well defined oncogenic alterations on the therapeutically relevant parameters of the micromilieu of malignant tumours.

Tumor tissue oxygenation as evaluated by computerized-po 2-histography

A computerized pO 2 measurement system with a novel electrode motion pattern (Sigma-pO 2-histography) was evaluated in vitro and in vivo. The system was found to be reliable in 0.9% saline and 10% hydroxyethylene starch solution and in fresh donor blood. Marked deviations were found in lipid and hemoglobin solutions and in fluorocarbon emulsions. Histograms obtained in rat liver, mouse muscle, and subcutis were similar to previously reported distributions. Direct comparison between Sigma-Eppendorf and self-constructed Whalen-type electrodes in hypoxic tumors gave similar results. A large series of measurements indicated that hypoxic and anoxic tissue areas were frequently found both in isografted rodent and in xenografted human tumors. The extent of oxygen deprivation depended on the cell line studied, tumor size, implantation site, the vascularity, and the actual tissue perfusion. Pentobarbital anesthesia redistributed the tumor oxygenation without affecting the median pO 2 value. Tumors growing in a pre-irradiated bed were less oxygenated than those at untreated sites. Hyperthermia at therapeutically relevant temperatures reduced pO 2 levels in adequately oxygenated tumors whereas little change was detected in poorly oxygenated tumors. First measurements in tumors in patients revealed marked inter- and intratumor heterogeneity. It is concluded that this novel technique is suitable for routine measurements of tissue oxygenation of solid tumors in situ.

Einflüsse von niedermolekularer Hydroxyäthylstärke (HÄS 40) im Vergleich zu Ringer–Lösung auf die Sauerstoffspannung des Skelettmuskels bei septischen Patienten

Volume expansion for the establishment of normal to slightly hyperdynamic systemic circulation has become part of a standard concept in the treatment of septicemic patients. The goal is an improvement of microcirculation with beneficial effects on tissue oxygen supply. This study investigates the effect of hydroxyethyl starch solution (HES 6%: mean molecular weight = 40,000) versus ringer's solution on tissue oxygen tensions in human skeletal muscle during periods of septicemia in 10 mechanically ventilated ICU-patients. Measurement of tissue oxygen tension was achieved by a polarographic pO2-sensitive flexible probe. After computer assisted analysis pO2-histograms were calculated out of 200 single pO2-values measured consecutively within a time period of 4 min. Infusions of 500 ml ringer's solution or 500 ml HES were given over 60 min in each patient in a randomized order. The second infusion was begun when the pO2-histogram had reproducibly regained control values as measured before treatment. Measurements were made every 30 min after starting the infusion for a total period of 150 min. As a result the median pO2 improved by 24.5% 90 min after the infusion of HES was begun with a simultaneous significant (30 to 150 min; p less than 0.05) drop in hematocrit from 34.3% to 32.4%. In contrast ringer's solution had no significant effect on tissue pO2 whereas the hematocrit was comparable to the HES group in the time period of 30-60 min. In both groups no linear correlation between hematocrit and pO2-tensions could be established. It remains unclear if pO2-tensions during and after HES infusion can be correlated to an improved capillary perfusion. However, as was clearly demonstrated, different types of solutions used for volume expansion may exert different effects on pO2-tissue tension in septic patients.

Early detection of shock in critically ill patients by skeletal muscle PO2 assessment.

The usefulness of skeletal muscle PO2 assessment in monitoring patients at risk of shock was evaluated in 20 critically ill patients. A shock score, inotropic score, and combined inotropic-shock score were calculated. If the median skeletal muscle PO2 assessment was more than 31.5 mm Hg, no shock occurred in the period from 4 hours before to 6 hours after the measurement. The risk of shock occurring during the first 2 hours after the skeletal muscle PO2 assessment was 2.2 times higher if median skeletal muscle PO2 assessment was below 22.5 mm Hg. If inotropes were administered, no significant difference was found in the incidence of shock if skeletal muscle PO2 was below or above 22.5 mm Hg. Skeletal muscle PO2 assessment enables the determination of the severity of shock and determination of risk of shock in critically ill patients, provided no treatment with inotropes has been instituted.

Minimum intracellular PO2 for maximum cytochrome turnover in red muscle in situ.

Probability distributions of myoglobin (Mb) saturation and intracellular PO2 were determined with subcellular spatial resolution in dog gracilis muscles during steady-state twitch contraction at 5-100% of maximal rate of O2 consumption (VO2). Calculations (Clark, A., and P. A.A. Clark. Biophys. J. 48: 931-938, 1985) and measurements (Gayeski, T. E. J., and C. R. Honig. Adv. Exp. Med. Biol. 200: 487-494, 1986) indicate that the PO2 in equilibrium with Mb is virtually identical to the PO2 at cytochrome aa3. Median intracellular PO2 and PO2 in the lower tails of probability distributions were poorly correlated with VO2. The variability of cell PO2 was greatly diminished when median PO2 was less than the PO2 for half saturation of MB, since Mb acts as a PO2 buffer. The lower tails of PO2 distributions contained almost no anoxic loci even when median PO2 was less than 1 Torr. VO2 was well correlated with the concentration ratio of phosphocreatine to free creatine (PCr/Crf) over a wide range of PO2. PO2 greater than or equal to 0.5 Torr supported maximal VO2 and energy demand. We conclude that 1) the mechanism of action of cytochrome aa3 is the same in red muscle in vivo as in mitochondria in vitro, and 2) an upper bound on the apparent Michaelis constant for maximal VO2 of red muscle is approximately 0.06 Torr.

Increase in tumor pO2 by perfluorochemicals and carbogen.

The effects of perfluorochemicals (Fluosol-DA) in combination with carbogen (95% O2 and 5% CO2) breathing on the tumor pO2 was investigated. The pO2 in RIF-1 tumors grown in the leg of C3H mice was determined by polarographic method using oxygen microelectrodes with diameters of 50-60 micron. The average and median pO2 in the control RIF-1 tumors was about 13 mm Hg and 6 mm Hg, respectively. Carbogen breathing alone could cause a significant increase in pO2 in some tumors and Fluosol-DA injection (i.v.) alone caused a slight change in tumor pO2. When the animals were treated with both Fluosol-DA injection and carbogen breathing, the pO2 markedly increased in most of the tumors resulting in an average and median tumor pO2 of 80 mm Hg and 60 mm Hg, respectively. Such an increase in tumor pO2 may account for the previous observations by us and others that the response of experimental tumors to radiation could be markedly increased by treating the tumor-bearing animals with carbogen and Fluosol-DA.

Muscle tissue oxygen pressure in patients with arterial occlusive disease

Oxygen pressure histograms were determined with the multiwire surface electrode from the gastrocnemius muscle in patients with arterial occlusive disease and compared with those of healthy volunteers. Seven out of 22 patients had normally distributed histograms like volunteers, but the mean PO 2 values were lower than the total mean value of the volunteers. Fifteen patients showed scattered histograms with dominating low PO 2 values. Ten out of 11 patients suffering from diabetes mellitus had scattered histograms. When perfusion pressure was impaired by elevating the leg or the musculature was stressed in 7 patients the histograms' form of all these patients changed significantly. Median PO 2 fell in all cases with clinically decompensated occlusive disease. Percutaneous transluminal angioplasty of an occlusion of the superficial femoral artery led to a significant shift of the histogram to higher PO 2 values. The scattered histograms of patients suffering from arterial occlusive disease are thought to be caused by an inhomogeneous blood flow probably induced by the closure of arterioles.

Erfahrungen mit der High-Frequency-Jet-Ventilation bei Eingriffen am Kehlkopf und an der Trachea

60 ENT patients were ventilated with the high frequency jet ventilation method, using endotracheal catheters during 50 cases of laryngeal and 10 cases of tracheal surgery. Ventilation was carried out with equipment of type MK 800 (Acutronic Ltd.) using the following parameters; rate: 150/min, insufflation time: 30-40%, pressure: 0.7-2.1 bar, and flow minute volume (FMV) 7-23 1. Anaesthesia was carried out with flunitrazepam or diazepam, fentanyl and succinylcholine. Surgical view was very good indeed, thanks to the thin jet catheter (4.7 mm outer diameter) in the trachea. At the low "tidal volumes" and intratracheal pressure changes when a rate of 150/min was used, no movement of the vocal cords was seen, so that microsurgery was easy to perform. There were no cases of hypoxia. The median pO2 value was 193 mm Hg. When a flow minute volume of 200 ml/kg was used for patients with normal lung function, and 250 ml/kg for those with impaired function, ventilation was quite adequate. The quality of ventilation should always be checked, and corrected as necessary, by blood gas analyses. Hypoventilation occurred when the FMV was less than 250 ml/kg in patients with decreased lung function, when the tip of the catheter was inserted into a mainstem bronchus or near to the tracheostoma, or when gas escape was obstructed. Unhampered gas escape must be present at all times, because otherwise intratracheal pressure rises and ventilation becomes insufficient. If the pressure increase is marked under these circumstances it can even lead to a pneumothorax.

PO2 and microflow histograms of the beating heart in response to changes in arterial pO2.

The influence of different values of arterial oxygen partial pressure (PO2) on local tissue PO2 was investigated. Tissue PO2 was measured on the surface of the beating hearts of rabbit and cat by the multiwire surface electrode as described by Kessler and Lübbers (21). In parallel experiments, local hydrogen clearance applying the H2-PH2 probe (33) was used to determine the mean blood flow per area (microflow) at the capillary level. Mean blood flow per area, v, was calculated from PH2 clearance curves obtained by local application of rectangular hydrogen pulses. The results are presented as histograms. Under steady state conditions (barbiturate narcosis), tissue PO2 ranged from 5 to 65 Torr (0.67 to 8.67 kPA) with a median of 31 Torr (4.13 kPA) in the cat heart. Mean flow per area covered values between 25 and 11 mum/s with a median of 55 mum/s. For rabbit heart muscle, the median was v = 37 mum/s and the range 28 to 46 mum/s. Hyperoxia broadened the range of tissue PO2 and shifted flow per area to lower values. Different degrees of hypoxia shifted the PO2 histogram to the left (median PO2 14 Torr and 4 Torr, respectively; [1.87 kPA and 0.53 kPA]) and the flow histogram to the right.