The role of prostaglandins in the realization of respiratory effects of TNF-α in case of hypoxia

At the present time very little is known about interactions between systemic inflammation and control of respiration. The aim of this study was to compare the respiratory effects of the main inflammatory cytokine TNF - α before and after pretreatment with diclofenac, a nonspecific cyclooxygenase (COX) inhibitor. In experiments on anesthetized, tracheostomized rats, pneumotachometry method was used to measure peak airflow and respiratory rate. The ventilatory response to hypoxia was investigated by the rebreathing method. It is shown that an increase in the systemic level of TNF – α causes a significant increase in the minute volume of respiration, tidal volume, the average speed of the inspiratory flow. In contrast the slope of the hypoxic ventilatory response decreased after administration of TNF-α. Diclofenac pretreatment eliminated these respiratory effects of TNF - α. The data indicate that the ability of TNF - α to enhance basal ventilation and to reduce the ventilatory hypoxic response is mediated by the cyclooxygenase pathway. Key words: tumor necrosis factor – α, hypoxia, prostaglandins, peripheral chemoreception, respiration.

Estimated plasma volume status is a modest predictor of true plasma volume excess in compensated chronic heart failure patients

Plasma volume and especially plasma volume excess is a relevant predictor for the clinical outcome of heart failure patients. In recent years, estimated plasma volume based on anthropometric characteristics and blood parameters has been used whilst direct measurement of plasma volume has not entered clinical routine. It is unclear whether the estimation of plasma volume can predict a true plasma volume excess. Plasma volume was measured in 47 heart failure patients (CHF, 10 female) using an abbreviated carbon monoxide rebreathing method. Plasma volume and plasma volume status were also estimated based on two prediction formulas (Hakim, Kaplan). The predictive properties of the estimated plasma volume status to detect true plasma volume excess > 10% were analysed based on logistic regression and receiver operator characteristics. The area under the curve (AUC) to detect plasma volume excess based on calculation of plasma volume by the Hakim formula is 0.65 (with a positive predictive value (PPV) of 0.62 at a threshold of − 16.5%) whilst the AUC for the Kaplan formula is 0.72 (PPV = 0.67 at a threshold of − 6.3%). Only the estimated plasma volume status based on prediction of plasma volume by the Kaplan formula formally appears as an acceptable predictor of true plasma volume excess, whereas calculation based on the Hakim formula does not sufficiently predict a true plasma volume excess. The low positive predictive values for both methods suggest that plasma volume status estimation based on these formulas is not suitable for clinical decision making.

Blood Volume, Hemoglobin Mass, and Peak Oxygen Uptake in Older Adults: The Generation 100 Study

Purpose: To investigate the association between blood volume, hemoglobin mass (Hbmass), and peak oxygen uptake (VO2peak) in healthy older adults.Methods: Fifty fit or unfit participants from the prospective randomized Generation 100 Study (n = 1,566) were included (age- and sex-specific VO2peak above or below average values). Blood, plasma, and erythrocyte volume and Hbmass were tested using the carbon monoxide rebreathing method within 1 week after VO2peak testing.Results: Mean age, BMI, Hbmass, blood volume, and VO2peak were 73.0 ± 2.1 years, 24.8 ± 3.3 kg·m2, 10.0 ± 1.7 g·kg−1, 76.4 ± 11.8 mL·kg−1, and 33.5 ± 8.4 mL·kg−1·min−1. VO2peak in fit and unfit participants and women and men were 38.6 ± 6.5 and 25.8 ± 3.8 mL·kg−1·min−1, 30.7 ± 7.6 mL·kg−1·min−1, and 35.5 ± 8.5 mL·kg−1·min−1, respectively. Women were shorter (Δ14 cm), leaner (Δ13 kg), and with less muscle mass (Δ9%) than men (P < 0.05). Relative erythrocyte volume and Hbmass were lower in women, and blood and erythrocyte volume and Hbmass were higher in the fit participants (P < 0.05). Hbmass and erythrocyte volume explained 40 and 37%, respectively, of the variability in VO2peak, with a limited effect of physical-activity adjustment (40 and 38%, respectively). Blood and plasma volume explained 15 and 25%, respectively, of VO2peak variability, and the association was strengthened adjusting for physical activity (25 and 31%, respectively), indicating a training-dependent adaptation in plasma but not erythrocyte volume (p ≤ 0.006).Conclusions: Blood and plasma volumes were moderately associated with VO2peak in healthy older men and women, and the association was strengthened after adjustment for physical activity. Hbmass and erythrocyte volume were strongly associated with VO2peak but unrelated to physical activity.

Ventilatory response to CO2 with Read's rebreathing method in normal infants

Background Methods of evaluating the ventilatory response to CO2 (VRCO2) of the respiratory center include the steady-state and the rebreathing method. Although the rebreathing method can evaluate the respiratory center more in detail, the steady-state method has been mainly performed in infants. The aim of this study was to investigate whether we could perform the VRCO2 with the rebreathing method in normal infants. Methods The subjects were 80 normal infants. The gestational age was 39.9（39.3-40.3）weeks, and the birth body weight was 3,142 (2,851-3,451) grams. We performed the VRCO2 with Read’s rebreathing method, measuring the increase in minute volume (MV) in response to the increase in EtCO2 by rebreathing a closed circuit. The value of VRCO2 was calculated as follow: VRCO2 (mL/min/mmHg/kg) = ΔMV / ΔEtCO2 / Body weight. Results We performed the examination without adverse events. The age in days at examination was 3 (2-4), and the examination time was 150±38 seconds. The maximum EtCO2 was 51.1 (50.5-51.9) mmHg. The value of VRCO2 was 34.6 (29.3-42.8). Tidal volume had a greater effect on the increase in MV than respiratory rate (5.4 to 14.3 mL/kg, 44.1 to 55.9 /min, respectively). Conclusion This study suggests that the rebreathing method can evaluate the ventilatory response to high blood CO2 in a short examination time. We conclude that the rebreathing method is useful even in infants. In the future, we plan to measure the VRCO2 of preterm infants, and evaluate the respiratory center of infants in more detail.

Noninvasive Assessment of Cardiac Output: Accuracy and Precision of the Closed‐Circuit Acetylene Rebreathing Technique for Cardiac Output Measurement

Background Accurate assessment of cardiac output is critical to the diagnosis and management of various cardiac disease states; however, clinical standards of direct Fick and thermodilution are invasive. Noninvasive alternatives, such as closed‐circuit acetylene (C 2 H 2 ) rebreathing, warrant validation. Methods and Results We analyzed 10 clinical studies and all available cardiopulmonary stress tests performed in our laboratory that included a rebreathing method and direct Fick or thermodilution. Studies included healthy individuals and patients with clinical disease. Simultaneous cardiac output measurements were obtained under normovolemic, hypovolemic, and hypervolemic conditions, along with submaximal and maximal exercise. A total of 3198 measurements in 519 patients were analyzed (mean age, 59 years; 48% women). The C 2 H 2 method was more precise than thermodilution in healthy individuals with half the typical error (TE; 0.34 L/min [ r =0.92] and coefficient of variation, 7.2%) versus thermodilution (TE=0.67 [ r =0.70] and coefficient of variation, 13.2%). In healthy individuals during supine rest and upright exercise, C 2 H 2 correlated well with thermodilution (supine: r =0.84, TE=1.02; exercise: r =0.82, TE=2.36). In patients with clinical disease during supine rest, C 2 H 2 correlated with thermodilution ( r =0.85, TE=1.43). C 2 H 2 was similar to thermodilution and nitrous oxide (N 2 O) rebreathing technique compared with Fick in healthy adults (C 2 H 2 rest: r =0.85, TE=0.84; C 2 H 2 exercise: r =0.87, TE=2.39; thermodilution rest: r =0.72, TE=1.11; thermodilution exercise: r =0.73, TE=2.87; N 2 O rest: r =0.82, TE=0.94; N 2 O exercise: r =0.84, TE=2.18). The accuracy of the C 2 H 2 and N 2 O methods was excellent ( r =0.99, TE=0.58). Conclusions The C 2 H 2 rebreathing method is more precise than, and as accurate as, the thermodilution method in a variety of patients, with accuracy similar to an N 2 O rebreathing method approved by the US Food and Drug Administration.