Arterial Blood Oxygen Tension Research Articles

THE INFLUENCE OF BIOCOMPATIBILITY OF THE EXTRACORPOREAL OXYGENATOR CIRCUIT ON THE DEGREE OF HEMOLYSIS AND OPTIMIZATION OF OXYGEN STATUS IN MINIMALLY INVASIVE CORONARY ARTERY BYPASS GRAFTING

Introduction. A distinctive feature of cardiopulmonary bypass in minimally invasive coronary artery bypass grafting (CABG) is the significantly longer perfusion time, involving active blood drainage from the vein to the cardiotomy reservoir, which carries the risk of hemolysis development. In this context, mechanical hemolysis disrupts the gas transport function of the blood.
 The aim of the research. Reducing hemolysis and optimizing oxygen status of patients during minimally invasive coronary artery bypass grafting surgeries.
 Materials and methods. The study included 60 patients, who underwent minimally invasive coronary artery bypass grafting (CABG) with cardiopulmonary bypass (CPB) under moderate hypothermia. The patients were divided into two groups of 30 individuals each. To improve the biocompatibility of the oxygenator, the circuit in Group 1 (Gr1) was treated with an adaptive composition, while in Group 2 (Gr2), the oxygenator circuit remained untreated. The following parameters were examined: hemoglobin (Hb), hematocrit (Ht), red blood cell count (RBC), oxygen delivery index (DO2I), oxygen consumption index (VO2I), oxygen extraction ratio (O2ER%), oxygen extraction index (O2EI%), venous (SpvO2), and arterial (SpaO2) oxygen saturation, oxygen tension in arterial (PaO2) and venous blood (PvO2), acid-base status of the blood (pH, pCO2,HCO3ˉ, BE), and the degree of hemolysis.
 Results. Before initiation of cardiopulmonary bypass (CPB), an insignificant increase in O2IE% was observed in Gr1 (26.07±1.57) and Gr2 (27.11±0.81); p=0.875, indicating an increase in tissue oxygen consumption. At the hypothermic stage CPB, both Gr1 and Gr2 demonstrated a statistically significant decrease in Hb, Ht, and RBC levels (p<0.05) due to hemodilution, accompanied by a decrease in IDO2, IVO2, O2IE%, and O2ER% in both groups due to hypothermia. After rewarming, O2ER% in Gr1 (22.91±2.68) and Gr2 (24.59±2.02); p=0.191, and O2EI% in Gr1 (22.92±2.44) and Gr2 (24.61±2.01); p=0.215, were in the normal range. After weaning off cardiopulmonary bypassin Gr2, O2EI% was 27.34±1.97, indicating an increase in oxygen consumption and oxygen extraction. Upon separation from CPB, Gr2 showed a tendency to mild compensated metabolic acidosis, mainly due to HCO3ˉ 21.9±0.3. During the rewarming stage, the hemolysis value was 0.36±0.09in Gr1 and 0.45±0.17 in Gr2 (p<0.001). After CPB, hemolysis was 0.41±0.15 in Gr1 and 0.61±0.22 in Gr2 (p<0.001).
 Conclusions. Improving the biocompatibility of the extracorporeal oxygenatorcircuit makes it possible to reduce hemolysis and optimise the patient's oxygen status after cardiopulmonary bypass in minimally invasive coronary artery bypass grafting.

Clinical effectiveness of phospholipids in patients with restrictive respiratory failure due to lung tissue inflammation

Objective — to analyze the clinical effectiveness use of phosphatidylcholine liposomes in the treatment of patients with restrictive respiratory failure caused by acute pneumonia and pneumonia with a prolonged course.
 Materials and methods. A prospective cohort study of 68 people was conducted on the basis of the pulmonology department of the Kirovohrad Regional Hospital of the Kirovohrad Regional State in 2020—2021. The people were divided into two groups: I (n = 20) — control group, II (n = 48) — experimental group. They were composed of men aged 25 to 40 years. The first group consisted of healthy individuals who underwent a preventive examination. The second group included patients who, in addition to the traditional treatment of pneumonia, were treated with phospholipids in liposomal form. The drug was used by inhalation according to the instructions. In the course of the experiment, the volume-time indicators of external respiration and gas exchange of the body were studied in dynamics.
 Results and discussion. The introduction of phospholipids in liposomal form had a positive effect on the restoration of the function of external respiration from the 5th day of treatment of the disease. This is evidenced by the gradual normalization of breathing rate and respiratory volume. It was shown that the ratio of alveolar ventilation and minute respiratory volume was significantly lower and ranged from 60.3 to 72.7 % (with a control value of 72.2 to 77.4 %). Oxygen consumption increased by approximately 76 % on the 5th day of the disease, which indicates a pronounced increase in the level of oxidative metabolism in the body during this pathological process. Recovery could be observed due to optimization of the body’s oxygen supply. Regarding carbon dioxide release, this indicator was almost 2.3 times higher than the control values ​​on the 5th day of the disease. This contributes to the development of metabolic acidosis, which in turn leads to respiratory alkalosis. Against the background of phosphatidylcholine liposomes treatment, this indicator gradually decreased and had a tendency to approach control values ​​a month after treatment (0.216 ± ± 0.042) l/min). Another of the studied indicators is the dead breathing space. According to this indicator, the efficiency of external breathing also increased. The minute volume of blood flow in healthy individuals was (6.5 ± 0.7). During the disease, it decreased to (4.7 ± 0.8) with gradual recovery, starting from the 10th day of treatment with phospholipids. There is also a decrease in the oxygen saturation of the arterial blood and a decrease in the use of oxygen, which can be judged by the characteristics of the venous blood; at the same time, the determined oxygen consumption increases due to hyperventilation. One month after the treatment, these indicators were no longer significantly different from the control values. A similar trend is noted in the analysis of oxygen tension in arterial and venous blood, with a gradual normalization of indicators against the background of the use of phosphatidylcholine liposomes. The determination of the alveolar-arterial difference in oxygen showed an increase in the indicator in the experimental group compared to the control group. Most of the indicators we studied contributed to the decrease in oxygen, thus increasing the efficiency of external respiration.
 Conclusions. Phosphatidylcholine liposomes are an effective means of complex therapy of pneumonia. The drug has a normalizing effect on the level of energy metabolism in the body and normalizes oxygen consumption, contributing to a faster recovery of the optimal intensity of metabolic processes.

Placental capillary pericytes release excess extracellular vesicles under hypoxic conditions inducing a pro-angiogenic profile in term pregnancy

Pericytes are multifunctional cells wrapped around capillary endothelia, essential for vascular health, development, and blood flow regulation, although their role in human placental chorionic villi has not been fully explored. The second half of normal pregnancy is characterized by a progressive decline in placental and fetal oxygen levels which, by term, comprises a substantial degree of hypoxia. We hypothesized this hypoxia would stimulate pericyte regulation of chorionic villous capillary function. This study's objective was to investigate the role of hypoxia on normal term placental pericytes (PLVP) and their signaling to endothelial cells. First, we confirmed fetoplacental hypoxia at term by a new analysis of umbilical arterial blood oxygen tension of 3,010 healthy singleton neonates sampled at caesarean section and before labor. We then measured the release of cytokines, chemokines, and small extracellular vesicles (PLVPsv), from PLVP cultured at 20%, 8% and 1% O2. As O2 levels decreased, secreted cytokines and chemokines [interleukin-6 (IL-6), interleukin-1α (IL-1α) and vascular endothelial growth factor (VEGF)], and small extracellular vesicle markers, (Alix, Syntenin and CD9) increased significantly in the culture supernatants. When primary human umbilical vein endothelial cells (HUVEC) were cultured with PLVPsv, polygon formation, number, and tube formation length was significantly increased compared to cells not treated with PLVPsv, indicating PLVPsv stimulated angiogenesis. We conclude that adding PLVPsv stimulates angiogenesis and vessel stabilization on neighboring endothelial cells in response to hypoxia in term pregnancy compared to no addition of PLVPsv. Our finding that PLVP can release angiogenic molecules via extracellular vesicles in response to hypoxia may apply to other organ systems.

Correlation Between Cerebral Tissue Oxygen Saturation and Oxygen Extraction Fraction During Anesthesia: Monitoring Cerebral Metabolic Demand-supply Balance During Vasopressor Administration.

The speculation that cerebral tissue oxygen saturation (SctO 2 ) measured using tissue near-infrared spectroscopy reflects the balance between cerebral metabolic rate of oxygen and cerebral oxygen delivery has not been validated. Our objective was to correlate SctO 2 with cerebral oxygen extraction fraction (OEF) measured using positron emission tomography; OEF is the ratio between cerebral metabolic rate of oxygen and cerebral oxygen delivery and reflects the balance between these 2 variables. This cohort study was based on data collected in a previously published trial assessing phenylephrine versus ephedrine treatment in anesthetized patients undergoing brain tumor surgery. The variables of interest were measured twice over the healthy hemisphere before surgery: the first measurement performed after anesthesia induction and the second measurement performed after induction of a ∼20% increase in blood pressure using either phenylephrine or ephedrine. Data from 24 patients were analyzed. The overall vasopressor-induced relative changes in SctO 2 (ΔSctO 2 ) and OEF (ΔOEF) were 3.16% [interquartile range, -0.73% to 6.04%] and -12.5% [interquartile range, -24.0% to -6.19%], respectively. ΔSctO 2 negatively correlated with ΔOEF after phenylephrine treatment (Spearman rank correlation coefficient [ rs ]=-0.76; P =0.007), ephedrine treatment ( rs =-0.76; P =0.006), and any treatment ( rs =-0.79; P <0.001). ΔSctO 2 significantly associated with ΔOEF based on multivariable analysis with ΔOEF, relative changes in mean arterial pressure, arterial blood oxygen tension, and the bispectral index as covariates ( P =0.036). The negative correlation between changes in SctO 2 and OEF suggests that SctO 2 may reflect the cerebral metabolic demand-supply balance during vasopressor treatment. The generalizability of our findings in other clinical scenarios remains to be determined.

Changes in Arterial Blood Pressure and Oxygen Tension as a Result of Hoisting in Isoflurane Anesthetized Healthy Adult Horses.

Background: In anesthetized adult horses, changes in recumbency can influence the cardiovascular system but how arterial blood pressures and oxygen tension change in isoflurane anesthetized animals as a direct result of hoisting has not been investigated.Objective: To evaluate effects of hoisting on hemodynamic function and pulmonary gas exchange in isoflurane-anesthetized horses.Study Design: Prospective, experimental study.Methods: Six adult horses were anesthetized three times using isoflurane in pure oxygen (inspired fraction 0.9–1.0), and allowed breathing spontaneously in lateral recumbency. After 45 min horses were hoisted using a single hoist-hobble system for 5 min and returned into left lateral recumbency. Heart rate (HR), respiratory rate (RR), and systolic (SAP), diastolic (DAP), and mean arterial blood pressures (MAP) were measured every minute starting from 5 min before to 5 min after hoisting. Arterial blood gas samples were collected before, during, and after hoisting.Results: Significant changes in hemodynamic parameters and PaO2 but not PaCO2 were found between baseline recordings and measurements obtained during and early after hoisting. The MAP decreased within the 1st min of hoisting from a mean of 74 ± 17 mmHg at baseline to 57 ± 20 mmHg (p < 0.05). Thereafter, it rapidly recovered to baseline before continuing to rise to higher than baseline values and then remaining elevated for 5 min after horses were returned into lateral recumbency. Simultaneously, the HR increased by 6–9 beats per min during the initial 3 min of hoisting before returning close to baseline values (p < 0.05). The PaO2 decreased significantly from a mean of 324.9 ±137.0 mmHg at baseline to a mean of 141.3 ± 104.2 mmHg during hoisting (p < 0.001) without recovering any more to baseline values.Clinical significance: Hoisting an adult horse during or at the end of isoflurane anesthesia carries the risk of a precipitous, though short-lived (1–2 min), drop in arterial blood pressures and a persistent decrease in arterial oxygenation. While in systemically healthy animals the observed functional impairments were not life-threatening, they may be more severe in systemically compromised horses.Therefore, arterial blood pressures and oxygenation must be carefully monitored when hoisting sick equine patients during or at the end of inhalant anesthesia.

Oxygen Regime of Skeletal Muscles in Teleost Fishes and the Mechanisms of Its Functional Correction (Short Review)

The data on the tension and diffusion of oxygen in the skeletal muscles of bony fish are summarized. The methods of the recording and calculation of these traits are compared. It is noted that oxygen diffusion in the skeletal muscles of bony fish is more complicated process than that in higher vertebrates. This process is supposed to be restrained by the membrane structures of muscle tissue cells. Particular attention is paid to the oxygen tension in arterial and venous blood and to the mechanisms of their functional correction. It is shown that the mentioned processes are governed by the humoral and neural control of gill blood flow, along with respiratory and cardiac activity. The contribution of receptors that are sensitive to oxygen and CO2 to the regulation of these functions is discussed.

Optimal Arterial Blood Oxygen Tension in the Early Postresuscitation Phase of Extracorporeal Cardiopulmonary Resuscitation: A 15-Year Retrospective Observational Study.

Hyperoxia could lead to a worse outcome after cardiac arrest. Few studies have investigated the impact of oxygenation status on patient outcomes following extracorporeal cardiopulmonary resuscitation. We sought to delineate the association between oxygenation status and neurologic outcomes in patients receiving extracorporeal cardiopulmonary resuscitation. Retrospective analysis of a prospective extracorporeal cardiopulmonary resuscitation registry database. An academic tertiary care hospital. Patients receiving extracorporeal cardiopulmonary resuscitation between 2000 and 2014. None. A total of 291 patients were included, and 80.1% were male. Their mean age was 56.0 years. The arterial blood gas data employed in the primary analysis were recorded from the first sample over the first 24 hours in the ICUs after return of spontaneous circulation. The mean PaO2 after initiation of venoarterial extracorporeal membrane oxygenation was 178.0 mm Hg, and the mean PaO2/FIO2 ratio was 322.0. Only 88 patients (30.2%) demonstrated favorable neurologic status at hospital discharge. Multivariate logistic regression analysis indicated that PaO2 between 77 and 220 mm Hg (odds ratio, 2.29; 95% CI, 1.01-5.22; p = 0.05) and PaO2/FIO2 ratio between 314 and 788 (odds ratio, 5.09; 95% CI, 2.13-12.14; p < 0.001) were both positively associated with favorable neurologic outcomes. Oxygenation status during extracorporeal membrane oxygenation affects neurologic outcomes in patients receiving extracorporeal cardiopulmonary resuscitation. The PaO2 range of 77 to 220 mm Hg, which is slightly narrower than previously defined, seems optimal. The PaO2/FIO2 ratio was also associated with outcomes in our analysis, indicating that both PaO2 and the PaO2/FIO2 ratio should be closely monitored during the early postcardiac arrest phase for postextracorporeal cardiopulmonary resuscitation patients.

Professional chronic obstructive pulmonary disease in combination with heart failure — clinical and functional features

Introduction. Heart failure increases the severity of symptoms and worsens the prognosis of chronic obstructive pulmonary disease (COPD) in smokers. Professional COPD is a separate phenotype, which suggests dif erences in the pat ern of comorbidity. Professional COPD in combination with heart failure has not been studied enough. T e aim of the study was to determine the relationship of heart failure c clinical, functional and hygienic characteristics of professional COPD. Materials and methods. T e one-center observational study included 115 patients with occupational chronic obstructive pulmonary disease (OCOPD). T e comparison group of 103 patients with COPD, smokers of tobacco. T e diagnosis of COPD met the criterion of GOLD 2011–2019. OCOPD patients were exposed to aromatic hydrocarbons with an excess of MPC in the air of working zone is 1.5 to 6 times, or of inorganic dust in the range of 2 to 9.5 MPC. Heart failure was diagnosed on the basis of any signs of myocardial dysfunction in echocardiography and/or elevation of the N-terminal precursor of cerebral natriuretic peptide (NT-pro-BNP) serum more than 125 PG/ml. the Groups were comparable in sex, age, durationof COPD, duration of action of exogenous etiological factor, causes of heart failure. Clinical and functional characteristics of COPD and heart failure were evaluated. For comparisons between groups for quantitative parameters used covariance analysis or test Kruskall-Wallis for comparison, the share of χ2 criterion. Relationships were determined by logistic regression. Results. In patients with OCOPD, the heart failure rate was higher — 63 (54.8%) cases compared to 38 (36.9%) in the group of COPD Smoking (p=0.009). Biventricular failure prevailed (44 (38.3%) patients) with preserved ejection fraction(47 (40.9%) cases). Right ventricular failure was detected in 15 (13.0%) of the subjects, lef ventricular failure — in 4 (3.5%), p=0.002. Echocardiography revealed severe pulmonary hypertension and diastolic myocardial dysfunction in the OCOPD group. OCOPD in combination with heart failure was characterized by CAT index values of more than 10 points, low exercise tolerance, a signif cant rate of decline in FEV1, a decrease in the partial tension of arterial blood oxygen, severe exacerbations of COPD. In multivariate analysis of the development of heart failure in patients with OCOPD predicted: length of service, systolic pressure in the pulmonary artery, partial oxygen tension of arterial blood, the test distance of six-minute walk. Conclusions. 1. OCOPD is characterized by a probability of heart failure — 54.8%. Biventricular failure with preserved ejection f action and predominant violation of diastolic myocardial function prevails. 2. T e subphenotype of OCOPD in combination with heart failure is characterized by severe symptoms, hypoxemia of rest, severe exacerbations of COPD.

The use of a virtual patient to follow changes in arterial blood gases associated with therapeutic thoracentesis.

Some controversies exist on the effect of therapeutic thoracentesis (TT) on arterial blood oxygen tension. The aim of this study was to evaluate this issue using a previously developed virtual patient. The analysis was based and supported by clinical data collected during 36 TT. Pleural pressure and transcutaneous oxygen and carbon dioxide pressures (PtcO2 and PtcCO2) were measured during pleural fluid withdrawal. Arterial blood oxygen tension and arterial CO2 tension (PaO2 and PaCO2) were analysed in simulations that mimicked TT. Minute ventilation was adjusted to maintain arterial CO2 tension at a constant level unless arterial blood oxygen tension fell below 8 kPa. Specifically, the influence of hypoxic pulmonary vasoconstriction efficiency was tested. In patients, PtcCO2 remained at an approximately constant level (average amplitude: 0.63 ± 0.29 kPa), while some fluctuations of PtcO2 were observed (amplitude: (1.65 ± 1.18 kPa) were observed. In 42% of patients, TT was associated with decrease in PtcCO2. Simulations showed the following: (a) there were similar PaO2 fluctuations in the virtual patient; (b) the lower the hypoxic pulmonary vasoconstriction efficiency, the more pronounced the PaO2 fall during fluid withdrawal; and (c) the lower the atelectatic lung areas recruitment rate, the slower the PaO2 normalization. The decrease in PaO2 was caused by an increase of pulmonary shunt. Therapeutic thoracentesis may cause both an increase and a decrease in PaO2 during the procedure. Pleural pressure decrease, caused by pleural fluid withdrawal, improves the perfusion of atelectatic lung areas. If the rate of recruitment of these areas is low, a lack of ventilation causes the arterial blood oxygen tension to fall. Effective hypoxic pulmonary vasoconstriction may protect against the pulmonary shunt.

Lack of association between arterial oxygen tensions in horses during exploratory coeliotomy and post-operative incisional complications: A retrospective study

The aim of this retrospective study was to determine if there was an association between the lowest arterial blood oxygen tensions (PaO2) measured during anaesthesia and post-operative incisional complications in horses. Clinical records of 278 horses undergoing ventral midline coeliotomy from 1 January 2010 to 31 December 2013 were examined.The frequency of incisional complications was 32.0% (n = 89). In a multivariable model, intra-operative arterial blood oxygen tensions (PaO2) were not significantly associated with development of an incisional complication (P = 0.351). Using hypertonic (7.2%) saline (P = 0.028, OR 3.167, 95% CI 1.132–8.861), increasing total plasma protein concentration (TP) (P = 0.002, OR 1.061 per g/L, 95% CI 1.021–1.102), an intestinal resection (P < 0.001, OR 4.056, 95% CI 2.231–9.323), increasing body mass (P = 0.004, OR 1.004 per kg, 95% CI 1.001–1.006) and the use of penicillin alone compared with penicillin and gentamicin pre-operatively (P = 0.009, OR 4.145, 95% CI 1.568–10.958) increased the risk of incisional complications. The study was unable to demonstrate a link between low intra-operative PaO2 and increased risk of post-operative incisional complications.

Hypoxia-induced increases in glucose uptake do not cause oxidative injury or advanced glycation end-product (AGE) formation in vascular endothelial cells.

An increase in glucose uptake by endothelial cells exposed to hyperglycemia is the presumed initiating event that causes systemic vascular disease in individuals with diabetes. Diabetics do not develop clinically significant pulmonary vascular disease, however, despite the pulmonary circulation’s exposure to the same level of glucose. We hypothesized that pulmonary artery endothelial cells are protected from the detrimental effects of hyperglycemia because they take up less glucose than endothelial cells in the systemic circulation, either because of intrinsic differences between the two cell types or because the lower oxygen tension in the pulmonary arterial blood depresses glucose uptake. To test this hypothesis, we exposed normoglycemic and hyperglycemic bovine pulmonary artery (PAECs) and aortic endothelial cells (AECs) from the same animal to progressively lower oxygen tensions and determined glucose uptake. In contrast with our initial hypothesis, we detected no significant difference in glucose uptake between the two cell types. Furthermore, glucose uptake in both PAECs and AECs increased, not decreased, as the oxygen tension dropped; this oxygen-dependent increase in glucose uptake in endothelial cells predominated over the hyperglycemia-mediated decrease in glucose uptake that has been reported by others. Despite the increase in glucose uptake at lower oxygen tensions, we detected no corresponding increase in protein carbonylation or advanced glycation endproducts. These results demonstrate that small physiologically relevant changes in oxygen tension can have an important impact on glucose uptake in endothelial cells. These results also demonstrate that an increase in glucose uptake, by itself, is not sufficient to generate ROS-mediated protein carbonylation or increase intracellular advanced glycation endproducts in vascular endothelial cells.

Pulmonary Gas Exchange and Exercise Capacity in Adults Born Preterm.

Preterm birth, and its often-required medical interventions, can result in respiratory and gas exchange deficits into childhood. However, the long-term sequelae into adulthood are not well understood. To determine exercise capacity and pulmonary gas exchange efficiency during exercise in adult survivors of preterm birth. Preterm (n = 14), very low birth weight (<1,500 g) adults (20-23 yr) and term-born, age-matched control subjects (n = 16) performed incremental exercise on a cycle ergometer to volitional exhaustion while breathing one of two oxygen concentrations: normoxia (fraction of inspired oxygen, 0.21) or hypoxia (fraction of inspired oxygen, 0.12). Ventilation, mixed expired gases, arterial blood gases, power output, and oxygen consumption were measured during rest and exercise. We calculated the alveolar-to-arterial oxygen difference to determine pulmonary gas exchange efficiency. Preterm subjects had lower power output at volitional exhaustion than did control subjects in normoxia (150 ± 10 vs. 180 ± 10 W; P = 0.01), despite similar normoxic oxygen consumption. However, during hypoxic exercise, there was no difference in power output at volitional exhaustion between the two groups (116 ± 10 vs. 135 ± 10 W; P = 0.11). Preterm subjects also exhibited a more acidotic, acid-base balance throughout exercise compared with control subjects. In contrast to other studies, adults born preterm, as a group developed a wider alveolar-to-arterial oxygen difference and lower PaO2 than did control subjects during normoxic but not hypoxic exercise. This study demonstrates that pulmonary gas exchange efficiency is lower in some adult survivors of preterm birth during exercise compared with control subjects. The gas exchange inefficiency, when present, is accompanied by low arterial blood oxygen tension. Preterm subjects also exhibit reduced power output. Overall, our findings suggest potential long-term consequences of extreme preterm birth and very low birth weight on cardiopulmonary function.

Measurement of the acute metabolic response to hypoxia in rat tumours in vivo using magnetic resonance spectroscopy and hyperpolarised pyruvate

PurposeTo estimate the rate constant for pyruvate to lactate conversion in tumours in response to a hypoxic challenge, using hyperpolarised 13C1-pyruvate and magnetic resonance spectroscopy. Methods and materialsHypoxic inspired gas was used to manipulate rat P22 fibrosarcoma oxygen tension (pO2), confirmed by luminescence decay of oxygen-sensitive probes. Hyperpolarised 13C1-pyruvate was injected into the femoral vein of anaesthetised rats and slice-localised 13C magnetic resonance (MR) spectra acquired. Spectral integral versus time curves for pyruvate and lactate were fitted to a precursor-product model to estimate the rate constant for tumour conversion of pyruvate to lactate (kpl). Mean arterial blood pressure (MABP) and oxygen tension (ArtpO2) were monitored. Pyruvate and lactate concentrations were measured in freeze-clamped tumours. ResultsMABP, ArtpO2 and tumour pO2 decreased significantly during hypoxia. kpl increased significantly (p<0.01) from 0.029±0.002s−1 to 0.049±0.006s−1 (mean±SEM) when animals breathing air were switched to hypoxic conditions, whereas pyruvate and lactate concentrations were minimally affected by hypoxia. Both ArtpO2 and MABP influenced the estimate of kpl, with a strong negative correlation between kpl and the product of ArtpO2 and MABP under hypoxia. ConclusionThe rate constant for pyruvate to lactate conversion, kpl, responds significantly to a rapid reduction in tumour oxygenation.

Evaluation of Renal Blood Flow and Oxygenation in CKD Using Magnetic Resonance Imaging

Animal studies suggest that progression of chronic kidney disease (CKD) is related to renal hypoxia. With renal blood supply determining oxygen delivery and sodium absorption being the main contributor to oxygen consumption, we describe the relationship between renal oxygenation, renal artery blood flow, and sodium absorption in patients with CKD and healthy controls. Cross-sectional study. 62 stable patients with CKD stages 3 to 4 (mean age, 61±13 [SD] years) and 24 age- and sex-matched controls. CKD versus control status. Renal artery blood flow, tissue oxygenation (relative changes in deoxyhemoglobin concentration of the renal medulla [MR2*] and cortex [CR2*]), and sodium absorption. Renal artery blood flow was determined by phase-contrast magnetic resonance imaging (MRI); MR2* and CR2* were determined by blood oxygen level-dependent MRI. Ultrafiltered and reabsorbed sodium were determined from measured glomerular filtration rate (mGFR) and 24-hour urine collections. mGFR in patients was 37% that of controls (36±15 vs 97±23 mL/min/1.73 m(2); P < 0.001), and reabsorbed sodium was 37% that of controls (6.9 vs 19.1 mol/24 h; P < 0.001). Single-kidney patient renal artery blood flow was 72% that of controls (319 vs 443 mL/min; P < 0.001). Glomerular filtration fraction was 9% in patients and 18% in controls (P < 0.001). Patients and controls had similar CR2* (13.4 vs 13.3 s(-1)) and medullary MR2* (26.4 vs 26.5 s(-1)) values. Linear regression analysis demonstrated no associations between R2* and renal artery blood flow or sodium absorption. Increasing arterial blood oxygen tension by breathing 100% oxygen had very small effects on CR2*, but reduced MR2* in both groups. Only renal artery blood flow was determined and thus regional perfusion could not be related to CR2* or MR2*. In CKD, reductions of mGFR and reabsorbed sodium are more than double that of renal artery blood flow, whereas cortical and medullary oxygenation are within the range of healthy persons. Reduction in glomerular filtration fraction may prevent renal hypoxia in CKD.

Changes of pathological and physiological indicators affecting drug metabolism in rats after acute exposure to high altitude.

High altitude environments cause the human body to undergo a series of pathological, physiological and biochemical changes, which have a certain effect on drug pharmacokinetics. The objective of the present study was to observe changes in factors affecting pharmacokinetics in rats following acute exposure to high altitude and return to low altitude. A total of 21 male Wistar rats were randomly assigned to three groups. The rats in group A were maintained at low altitude in Shanghai, 55 m above sea level; those in group B were acutely exposed to high altitude in Maqu, Gansu, 4,010 m above sea level; and those in group C were acutely exposed to high altitude and then returned to low altitude. Blood was collected from the orbit for the analysis of significant biochemical indicators and from the abdominal aorta for blood gas analysis. Brain, lung and kidney tissues were removed to observe pathological changes. In group B, the pH, buffer base (BB), base excess (BE), total carbon dioxide content (ctCO2), oxygen saturation of arterial blood (sO2), oxygen tension of arterial blood (pO2), serum sodium (Na+) concentration, lactate dehydrogenase (LDH) activity and total protein (TP) level were significantly reduced, and the carbon dioxide tension of arterial blood (pCO2), serum chloride (Cl−) concentration, serum total bilirubin (TBIL) level and alkaline phosphatase (ALP) activity were significantly increased compared with those in group A (P<0.05). In group C, the pH, BB, BE, sO2, pO2, hemoglobin (Hb) level, serum Na+ concentration, LDH activity and TP level were significantly reduced, and the pCO2, serum Cl− concentration, alanine transaminase activity, TBIL and urea levels were significantly increased (P<0.05) compared with those in group A. The Hb and ALP levels in group C were significantly lower than those in group B (P<0.05); and the TP, TBIL and urea levels in group C were significantly higher than those in group B (P<0.05). Pathological observation revealed that the alveolar wall was hyperemic, edematous and incrassate, the alveolar epithelium was hyperplastic and infiltrated with neutrophilic granulocytes and the alveolar septum was widened; brain neurons were edematous with enlarged perivascular spaces, and hippocampal neurons were metamorphic and karyopyknotic; and kidney mesangial cells were hyperplastic, both following acute exposure to high altitude and after returning to low altitude. In conclusion, blood gas indices, biochemical indicators and functions of the heart, liver, kidney were significantly changed, and marked pathological changes occurred in the brain, liver and kidney following acute exposure to high altitude and also after returning to low altitude. These changes are likely to seriously affect the pharmacokinetics of drugs.

Effect of verapamil and nitroglycerin on transplanted lung function in canines

To investigate the protective effect of combined administration of verapamil and nitroglycerin on the function of canine transplanted lungs. Twenty orthotopic left lung transplantations were performed in 40 canines, which were randomly divided into 4 groups. In group I (control), the donor lungs were perfused and preserved with LPD solution, while group II with LPD solution plus verapamil 0.1 g/L, group III with LPD solution plus nitroglycerin 0.1g/L, and group IV with LPD solution plus verapamil 0.1 g/L and nitroglycerin 0.1 g/L. Hemodynamics and graft gas exchange were assessed 0, 2 and 4 h after the operation. The lung grafts were harvested to measure the wet/dry weight ratio, malondialdehyde (MDA) contents and superoxide dismutase (SOD) activity. Compared with group I, II and III, the mean pulmonary artery pressure (MPAP), pulmonary vascular resistance index (PVRI), partial pressure of oxygen in arterial blood (PaO₂), dynamic compliance (Cdyn) and alveolar-arterial oxygen tension volume [P(A- a)O₂] in group IV were improved significantly (P<0.05). No significant difference in the partial pressure of carbondioxide (PaCO₂) and peak inspiratory pressure (PIP) was observed in the 4 groups (P>0.05). In group IV, the wet/dry weight ratio and MDA contents were lower than those in the other 3 groups, and the SOD activity was significantly higher than that of the other 3 groups (P<0.05). Verapamil and nitroglycerin in LPD solution can protect the respiratory function of canine lung grafts by attenuating pulmonary edema and oxidative stress.

Oxygen tension variation in ischemic gastrocnemius muscle, marrow, and different hypoxic conditions in vitro.

BackgroundBone marrow stromal cells (BMSCs) play an important role in ischemic limb angiogenesis. BMSCs cultured in vitro can be exposed to oxygen tension much higher than that experienced in vivo. This study assessed oxygen tension in bone marrow and ischemic muscle in vivo, and then identified an appropriate oxygen concentration for culturing BMSCs.Material/MethodsUnilateral hind limb ischemia was surgically induced in 30 mice, and tissue oxygen tension in bilateral gastrocnemius muscles and femoral bone marrow was monitored in vivo using a micro-electrode at 24 hours, 1 week, 2 weeks, and 3 weeks after modeling. Media used for culturing normal marrow, muscle, and artery tissue were incubated with various oxygen concentrations, and O2 tension was continuously monitored. Oxygen tension in aortic arterial blood was monitored using a micro-electrode and blood gas analyzer, and the results were compared.ResultsOxygen tension in ischemic gastrocnemius muscle reached a nadir at 1 week after ischemic modeling, when histological changes were most noticeable. Culture media incubated with 3%, 6%, and 14% oxygen (the normal oxygen levels of bone marrow, muscle, and arterial blood, respectively) required 9, 6, and 2 hours, respectively, to reach an equilibrated oxygen tension, and oxygen tension was elevated by 1.6-, 1.2-, and 0.4-fold, respectively, upon re-exposure of the media to air.ConclusionsPhysiological oxygen tension differs in different tissues. A 3% O2 concentration mimics the physiological O2 exposure experienced by BMSCs and represents the hypoxic concentration. Culture medium incubated under hypoxic conditions requires a prolonged period of time to regain equilibrated oxygen tension.

One of these things is not like the other: the heterogeneity of the cerebral circulation

The human cerebral vasculature is highly sensitive to changes in arterial blood gases (i.e. arterial carbon dioxide () and oxygen () tensions), such that hypercapnia/hypoxia and hypocapnia/hyperoxia cause global increases and decreases in cerebral blood flow. It is generally accepted that all cerebral arter-ioles – traditionally considered to be the regulators of brain blood flow – are equally sensitive to changes in arterial blood gases. However, this classic dogma may not be the case.

Aminophylline, administered at usual doses for rodents in pharmacological studies, induces hippocampal neuronal cell injury under low tidal volume hypoxic conditions in guinea-pigs

To establish whether aminophylline, administered at usual doses for rodents in pharmacological studies, induces brain injury in systemic hypoxaemia in guinea-pigs. A hypoxaemia (partial oxygen tension of arterial blood (PaO₂) = 40-60 mmHg) model was developed by low tidal volume mechanical ventilation in guinea-pigs. Under hypoxic conditions, aminophylline significantly increased the concentration of brain-specific creatine kinase in the serum in a dose- and time-dependent manner. A reduced number of hippocampal neuronal cells in the CA1 region, an increase in the concentration of neuron-specific enolase (NSE) in cerebrospinal fluid (CSF), an increase in lipid hydroperoxides and a decrease in the ratio of glutathione to glutathione disulfide in the brain tissues were also observed. These effects were not observed when aminophylline at the same doses was administered under normoxic conditions (PaO₂ = 80-100 mmHg). There was no difference in either serum or CSF concentrations of theophylline between normoxic and hypoxic conditions. Another methylxanthine, caffeine, did not increase the concentration of NSE in CSF. Aminophylline potentially induces brain damage under hypoxic conditions. We suggest that aminophylline treatment has adverse effects in patients with hypoxaemia subsequent to respiratory disorders such as asthma.

Effect of Ca-antagonists on pulmonary blood flow during single-lung ventilation in the dog

Experiments were conducted in 21 adult mongrel dogs to clarify the effects of Ca-antagonist (nifedipine sublingual administration 2.5 mg or 5 mg, or nicardipine intravenous administration 30 micrograms/kg or 60 micrograms/kg) on pulmonary blood flow under the condition of collapsed lung on the side of thoracotomy. Under anesthesia, an endotracheal tube with a movable blocker was used to intubate the trachea and the thoracotomized lung was collapsed. Subsequently, a Ca-antagonist was given and the ratio of the left main pulmonary artery/ascending thoracic aorta blood flow was used as an index of hypoxic pulmonary vasoconstriction (HPV). The following results were obtained. 1. Ca-antagonist administration under lung-collapse on the thoracotomy side resulted in inhibition of HPV of the collapsed lung, whereas, arterial blood oxygen tension (PaO2) remained in the acceptable range. 2. The maintenance of the lowered PaO2 within the acceptable range may have been due to the increase in cardiac output and the elevation of mixed venous blood oxygen tension resulting from Ca-antagonist administration, as well as the residual HPV even after administration of the Ca-antagonist.