Does venous blood gas analysis provide accurate estimates of hemoglobin oxygen affinity?

Alterations in hemoglobin oxygen affinity can be detected by exposing blood to different PO2 and recording oxygen saturation, a method termed tonometry. It is the gold standard to measure the PO2 associated with 50% oxygen saturation, the index used to quantify oxygen affinity (P50Tono). P50Tono is used in the evaluation of patients with erythrocytosis suspected to have hemoglobin with abnormal oxygen affinity. Since tonometry is labor intensive and not generally available, we investigated whether accurate estimates of P50 could also be obtained by venous blood gas analysis, co-oximetry, and standard equations (P50Ven). In 50 patients referred for evaluation of erythrocytosis, pH, PO2, and oxygen saturation were measured in venous blood to estimate P50Ven; P50Tono was measured for comparison. Agreement among P50Ven and P50Tono was evaluated (Bland-Altman analysis). Mean P50Tono was 25.8 (range 17.4-34.1)mmHg. The mean difference (bias) of P50Tono-P50Ven was 0.5mmHg; limits of agreement (95% confidence limits) were −5.2 to +6.1mmHg. The sensitivity and specificity of P50Ven to identify the 25 patients with P50Tono outside the normal range of 22.9-26.8mmHg were 5 and 77%, respectively. We conclude that estimates of P50 based on venous blood gas analysis and standard equations have a low bias compared to tonometry. However, the precision of P50Ven is not sufficiently high to replace P50Tono in the evaluation of individual patients with suspected disturbances of hemoglobin oxygen affinit

Effect of hypoxia and hyperoxia on exercise performance in healthy individuals and in patients with pulmonary hypertension: A systematic review

Exercise performance is determined by oxygen supply to working muscles and vital organs. In healthy individuals, exercise performance is limited in the hypoxic environment at altitude, when oxygen delivery is diminished due to the reduced alveolar and arterial oxygen partial pressures. In patients with pulmonary hypertension, exercise performance is already reduced near sea level due to impairments of the pulmonary circulation and gas exchange and, presumably, these limitations are more pronounced at altitude. In studies performed near sea level in healthy subjects as well as in patients with pulmonary hypertension (PH) maximal performance during progressive ramp exercise and endurance of submaximal constant load exercise were substantially enhanced by breathing oxygen-enriched air. Both in healthy individuals and in PH-patients these improvements were mediated by a better arterial, muscular and cerebral oxygenation along with a reduced sympathetic excitation, as suggested by the reduced heart rate and alveolar ventilation at submaximal isoloads, and an improved pulmonary gas exchange efficiency, especially in patients with PH. In summary, in healthy individuals and in patients with pulmonary hypertension, alterations in the inspiratory PO2 by exposure to hypobaric hypoxia or normobaric hyperoxia reduce or enhance exercise performance, respectively, by modifying oxygen delivery to the muscles and the brain, by effects on cardiovascular and respiratory control and by alterations in pulmonary gas exchange. The understanding of these physiologic mechanisms helps counselling individuals planning altitude or air travel and prescribing oxygen therapy to patients with pulmonary hypertension

Palmityl Coenzyme A Inhibition of Fatty Acid Synthesis

The effects of acyl-CoA derivatives (C8 to C20) on the activity of the fatty acid synthetases from yeast and Corynebacterium diphtheriae have been examined. Both enzyme systems are inhibited by the longer chain acyl thioesters (C16 to C20) and protected against this inhibition by bovine serum albumin (BSA). Identical relief from acyl-CoA inhibition is provided by the 6-0-methylglucose-containing lipopolysaccharide (MGLP), from Mycobacterium phlei. It is shown that MGLP forms a stable complex with palmitylCoA. This interaction accounts for the BSA-like effects of the polysaccharide. BSA and MGLP have two further effects on the fatty acid synthetases under study, also attributable to complex formation with palmityl-CoA. They stimulate the rate of over-all synthesis from acetyl-CoA and malonyl-CoAt and they cause a shift of the fatty acid pattern towards products of shorter chain length. The observed effects are discussed in terms of the regulation of fatty acid synthesis both with respect to rate and product composition. It is concluded that in the two microbial enzyme systems negative feedback inhibition and its relief are important control mechanisms

Automatic Processing of Nasal Pressure Recordings to Derive Continuous Side-Selective Nasal Airflow and Conductance

Monitoring of nasal airflow and conductance provides crucial insights into the variable nature of the nasal resistance, nasal cycle, and ventilation. We have previously shown that tracking of pressure swings at the entrance of each nasal passage by a dedicated catheter system allows bilateral monitoring of nasal airflow over several hours but requires complex linearization and calibration procedures. Side-selective nasal conductance is derived from linearized and calibrated bilateral nasal pressure swings and corresponding driving pressure, i.e., the transnasal pressure difference derived from an epipharyngeal catheter. Manual analysis of such recordings and computation of instantaneous conductance as the ratio of flow to driving pressure over several hours is extremely tedious, time consuming, and therefore not suitable for routine practice. To address this point, we developed and validated a software for automatic processing of nasal and epipharyngeal pressure recordings as a convenient tool for studying the nasal ventilation. The software applies an eight-parameter logistic model to transform nasal pressure swings into side-selective estimates of airflow that are calibrated and further processed along with epipharyngeal pressure to compute bilateral nasal conductance over consecutive, user-selectable time-segments. Essential processing steps include (1) offset correction, (2) low-pass filtering, (3) cross-correlation, (4) cutting of signals into individual breaths, (5) normalization, (6) ensemble averaging to obtain a mean pressure signal for each nasal side, (7) derivation of airflow, conductance, and further variables. Among four evaluated algorithms for calculation of nasal conductance, the derivative of the airflow-pressure curve according to the mean value theorem agreed closest with the gold standard, i.e., the conductance derived from airflow measured by a pneumotachograph attached to an oral-nasal mask and transnasal pressure. In combination with the nasal catheter system, our novel software represents a valuable tool for use in clinical practice and research to conveniently investigate nasal ventilation and its changes occurring spontaneously or in response to various exposures and therapeutic interventions

Coronal thick CT reconstruction: an alternative for initial chest radiography in trauma patients

It has been proposed that the imaging workup of trauma patients be accelerated by omitting the initial chest radiography (CR) and directly performing a computed tomography (CT); however, the baseline CR is then lacking. The purpose of this study was to assess if coronal thick reconstructions generated from chest CT could present an adequate alternative for CR. Sixty trauma patients underwent bedside CR and multidetector row chest CT in the emergency room. The image quality of thoracic anatomical structures, the diagnostic accuracy for chest pathology, and the depiction of indwelling devices were assessed on both modalities. Main pulmonary arteries and perihilar bronchi were equally visualized with both modalities. Central bronchi, retrocardial lung parenchyma, diaphragm, descending aorta, and vertebral pedicles were better visualized on thick CT reconstructions, whereas peripheral lung vessels were better depicted on CR (p<0.05). The accuracy to delineate various pathological findings did not differ between both modalities, except for a higher sensitivity to diagnose bronchial cuffing on CR (p<0.05). The location of indwelling devices was similarly and correctly depicted with both modalities. Coronal thick CT reconstructions provide a similar image quality and diagnostic accuracy compared with CR. These reconstructions may serve as an equivalent baseline image in trauma patients in whom emergency radiological evaluation has to be accelerate

The effects of continuous positive airway pressure therapy withdrawal on cardiac repolarization: data from a randomized controlled trial†

Aims The preliminary evidence supports an association between obstructive sleep apnoea (OSA), disturbed cardiac repolarization, and consequent cardiac dysrhythmias. The aim of the current trial was to assess the effects of continuous positive airway pressure (CPAP) therapy withdrawal on the measures of cardiac repolarization in patients with OSA. Methods and results Forty-one OSA patients established on CPAP treatment were randomized to either CPAP withdrawal (subtherapeutic CPAP) or continue therapeutic CPAP for 2 weeks. Polysomnography was performed, and indices of cardiac repolarization (QTc, TpTec intervals) and dispersion of repolarization (TpTe/QT ratio) were derived from 12-lead electrocardiography (ECG) at baseline and 2 weeks. Continuous positive airway pressure withdrawal led to a recurrence of OSA. Compared with therapeutic CPAP, subtherapeutic CPAP for 2 weeks was associated with a significant increase in the length of the QTc and TpTec intervals (mean difference between groups 21.4 ms, 95% CI 11.3-1.6 ms, P < 0.001 and 14.4 ms, 95% CI 7.2-21.5 ms, P < 0.001, respectively) and in the TpTe/QT ratio (mean difference between groups 0.02, 95% CI 0.00-0.03, P = 0.020). There was a statistically significant correlation between the change in apnoea/hypopnoea index (AHI) from baseline, and both the change in the QTc interval and the TpTec interval (r = 0.60, 95% CI 0.36-0.77, P < 0.001 and r = 0.45, 95% CI 0.17-0.67, P = 0.003, n = 41, respectively). Conclusion Continuous positive airway pressure withdrawal is associated with the prolongation of the QTc and TpTec intervals and TpTe/QT ratio, which may provide a possible mechanistic link between OSA, cardiac dysrhythmias, and thus sudden cardiac deat

Partial Pressure of Arterial Oxygen in Healthy Adults at High Altitudes: A Systematic Review and Meta-Analysis

Importance: With increasing altitude, the partial pressure of inspired oxygen decreases and, consequently, the Pao$_{2}$ decreases. Even though this phenomenon is well known, the extent of the reduction as a function of altitude remains unknown. Objective: To calculate an effect size estimate for the decrease in Pao$_{2}$ with each kilometer of vertical gain among healthy unacclimatized adults and to identify factors associated with Pao$_{2}$ at high altitude (HA). Data Sources: A systematic search of PubMed and Embase was performed from database inception to April 11, 2023. Search terms included arterial blood gases and altitude. Study Selection: A total of 53 peer-reviewed prospective studies in healthy adults providing results of arterial blood gas analysis at low altitude (&amp;lt;1500 m) and within the first 3 days at the target altitude (≥1500 m) were analyzed. Data Extraction and Synthesis: Primary and secondary outcomes as well as study characteristics were extracted from the included studies, and individual participant data (IPD) were requested. Estimates were pooled using a random-effects DerSimonian-Laird model for the meta-analysis. Main Outcomes and Measures: Mean effect size estimates and 95% CIs for reduction in Pao$_{2}$ at HA and factors associated with Pao$_{2}$ at HA in healthy adults. Results: All of the 53 studies involving 777 adults (mean [SD] age, 36.2 [10.5] years; 510 men [65.6%]) reporting 115 group ascents to altitudes between 1524 m and 8730 m were included in the aggregated data analysis; 13 of those studies involving 305 individuals (mean [SD] age, 39.8 [13.6] years; 185 men [60.7%]) reporting 29 ascents were included in the IPD analysis. The estimated effect size of Pao$_{2}$ was −1.60 kPa (95% CI, −1.73 to −1.47 kPa) for each 1000 m of altitude gain (τ$^{2}$ = 0.14; I$^{2}$ = 86%). The Pao$_{2}$ estimation model based on IPD data revealed that target altitude (−1.53 kPa per 1000 m; 95% CI, −1.63 to −1.42 kPa per 1000 m), age (−0.01 kPa per year; 95% CI, −0.02 to −0.003 kPa per year), and time spent at an altitude of 1500 m or higher (0.16 kPa per day; 95% CI, 0.11-0.21 kPa per day) were significantly associated with Pao$_{2}$. Conclusions and Relevance: In this systematic review and meta-analysis, the mean decrease in Pao$_{2}$ was 1.60 kPa per 1000 m of vertical ascent. This effect size estimate may improve the understanding of physiological mechanisms, assist in the clinical interpretation of acute altitude illness in healthy individuals, and serve as a reference for physicians counseling patients with cardiorespiratory disease who are traveling to HA regions

Obesity associated with increased brain age from midlife.

Common mechanisms in aging and obesity are hypothesized to increase susceptibility to neurodegeneration, however, direct evidence in support of this hypothesis is lacking. We therefore performed a cross-sectional analysis of magnetic resonance image-based brain structure on a population-based cohort of healthy adults. Study participants were originally part of the Cambridge Centre for Ageing and Neuroscience (Cam-CAN) and included 527 individuals aged 20-87 years. Cortical reconstruction techniques were used to generate measures of whole-brain cerebral white-matter volume, cortical thickness, and surface area. Results indicated that cerebral white-matter volume in overweight and obese individuals was associated with a greater degree of atrophy, with maximal effects in middle-age corresponding to an estimated increase of brain age of 10 years. There were no similar body mass index-related changes in cortical parameters. This study suggests that at a population level, obesity may increase the risk of neurodegeneration.This work was supported by the Bernard Wolfe Health Neuroscience Fund and the Wellcome Trust (grant number RNAG/259). The Cambridge Centre for Ageing and Neuroscience (Cam-CAN) research was supported by the Biotechnology and Biological Sciences Research Council (grant number BB/H008217/1).This is the final version of the article. It first appeared from Elsevier via http://dx.doi.org/10.1016/j.neurobiolaging.2016.07.01