Arterial PO2 Values Research Articles

Physiologic Effects of Extracorporeal Membrane Oxygenation in Patients with Severe Acute Respiratory Distress Syndrome.

Rationale: Blood flow rate affects mixed venous oxygenation (SvO2) during venovenous extracorporeal membrane oxygenation (ECMO), with possible effects on the pulmonary circulation and the right heart function. Objectives: To describe the physiologic effects of different levels of SvO2 obtained by changing ECMO blood flow in patients with severe acute respiratory distress syndrome receiving ECMO and controlled mechanical ventilation. Methods: Low (SvO2 target, 70-75%), intermediate (SvO2 target, 75-80%), and high (SvO2 target, >80%) ECMO blood flows were applied for 30 minutes in random order in 20 patients. Mechanical ventilation settings were left unchanged. The hemodynamic and pulmonary effects were assessed with pulmonary artery catheter and electrical impedance tomography. Measurements and Main Results: Cardiac output decreased from low to intermediate and to high blood flow/SvO2 (9.2 [6.2-10.9] vs. 8.3 [5.9-9.8] vs. 7.9 [6.5-9.1] L/min; P = 0.014), as well as mean pulmonary artery pressure (34 ± 6 vs. 31 ± 6 vs. 30 ± 5 mm Hg; P < 0.001) and right ventricular stroke work index (14.2 ± 4.4 vs. 12.2 ± 3.6 vs. 11.4 ± 3.2 g × m/beat/m2; P = 0.002). Cardiac output was inversely correlated with mixed venous and arterial Po2 values (R2 = 0.257; P = 0.031; and R2 = 0.324; P = 0.05). Pulmonary artery pressure was correlated with decreasing mixed venous Po2 (R2 = 0.29; P < 0.001) and with increasing cardiac output (R2 = 0.378; P < 0.007). Measures of [Formula: see text]/[Formula: see text] mismatch did not differ between the three steps. Conclusions: In patients with severe acute respiratory distress syndrome, increased ECMO blood flow rate resulting in higher SvO2 decreases pulmonary artery pressure, cardiac output, and right heart workload.

Validation of a new combined transcutaneous tcPCO2 and tcPO2 sensor in children in the operating theater.

BackgroundArterial blood gas analysis is the gold standard for monitoring of PaCO2 and PaO2 during mechanical ventilation. However, continuous measurements would be preferred. Transcutaneous sensors continuously measure blood gases diffusing from the locally heated skin. These sensors have been validated in children mostly in intensive care settings. Accuracy in children during general anesthesia is largely unknown.AimsWe conducted a study in children undergoing general anesthesia to validate the use and to determine the accuracy of continuous transcutaneous measurements of the partial pressures of PCO2 (tcPCO2) and PO2 (tcPO2).MethodsA prospective observational study in a tertiary care pediatric hospital in The Netherlands, from April to October 2018, in children aged 0–18 years undergoing general anesthesia. Patients were included when endotracheally intubated and provided with an arterial catheter for regular blood sampling. Patients with a gestational age <31 weeks, burn victims, and patients with skin disease were excluded. TcPCO2 and tcPO2 measurements were performed with a SenTec OxiVenT™ sensor (SenTec AG). Accuracy was determined with an agreement analysis between arterial and transcutaneous PCO2 and PO2 values, and between arterial and endtidal PCO2 (etCO2) values, according to Bland and Altman, accounting for multiple measurements per subject.ResultsWe included 53 patients (median age 4.1 years, IQR 0.7–14.4 years) and retrieved 175 samples. TcPCO2‐PaCO2 agreement analysis provided a bias of 0.06 kPa (limits of agreement (LOA) −1.18 to 1.31), the etCO2‐PaCO2 agreement showed a bias of −0.31 kPa (LOA −1.38 to 0.76). Results of the tcPO2‐PaO2 agreement showed a bias of 3.40 to 0.86* (mean tension) kPa.ConclusionsThis study showed good agreement between PaCO2 and tcPCO2 in children of all ages during general anesthesia. Both transcutaneous and endtidal CO2 measurements showed good accuracy. TcPO2 is only accurate under 6 months of age.

Comparison of Nasal bi-level Positive Airway Pressure Versus High-flow Nasal Cannula as a Means of Noninvasive Respiratory Support in Pediatric Cardiac Surgery.

Background:Noninvasive respiratory support is often used in preventing postextubation respiratory failure in neonates and infants after cardiac surgery.Aim:We compared the efficacy of nasal Bilevel Positive Airway Pressure (N/BiPAP) with that of High- flow Nasal Cannula(HFNC) in prevention of post extubation respiratory failure and maintenance of gas exchange in neonates and infants undergoing cardiac surgery. The incidence of complications related to the use of these modes were also compared.Settings and Design:This is a retrospective review of medical records of patients in pediatric cardiac intensive unit of a high-volume center.Methods:A total of 100 patients who received noninvasive respiratory support postextubation were divided into N/BiPAP group and HFNC group. The two groups were compared for postextubation respiratory failure, gas exchange in arterial blood gas at 24 h of extubation, and incidence of complications, namely pneumothorax, abdominal distension, and device–interface-related pressure ulcers.Results:Fifty patients each received N/BiPAP and HFNC after extubation. Patients who received N/BiPAP were younger (2.68 ± 2.97 months vs. 6.94 ± 4.04 months, P = 0.001) and had longer duration of postoperative ventilation (106.98 ± 79.02 h vs. 62.72 ± 46.14 h, P = 0.001). The reintubation rates were similar (20% [n = 10] in N/BiPAP group vs. 8% [n = 4] in HFNC group, P = 0.074). The mean arterial PO2 values at 24 h of extubation was 119.17 ± 56.07 mmHg for N/BiPAP group versus 123.32 ± 64.33 mmHg for HFNC group (P = 0.732). Arterial PCO2 values at 24 h were similar (43.97 ± 43.64 mmHg in N/BiPAP vs. 37.67 ± 4.78 mmHg in HFNC, P = 0.318). N/BiPAP group had higher incidence of abdominal distension (16% [n = 8] vs. nil in HFNC group, P = 0.003) and interface-related pressure ulcers (86% [n = 43] vs. 14% [n = 7] P = 0.006).Conclusion:N/BiPAP and HFNC have comparable efficacy in preventing reintubation and maintaining gas exchange. HFNC has fewer complications compared to N/BiPAP.

Comparison of arterial and venous blood gases in patients with obesity hypoventilation syndrome and neuromuscular disease.

OBJECTIVES:Obesity hypoventilation syndrome (OHS) and some neuromuscular diseases (NMD) present with hypercapnic respiratory failure. Arterial blood gas (ABG) analysis is important in the diagnosis, follow-up, and treatment response of these diseases. However, ABG sampling is difficult in these patients because of excessive subcutaneous fat tissue, muscle atrophy, or contracture. The aim of this study is to investigate the value of venous blood gas (VBG), which is an easier and less complicated method, among stable patients with OHS and NMD.METHODS:The study included stable OHS and NMD patients who had been previously diagnosed and followed up between March 2017 and May 2017 in the outpatient clinic. ABG was taken from all patients in room air, and peripheral VBG was taken within 5 min after ABG sampling.RESULTS:Thirty-six patients with OHS and 46 patients with NMD were included in the study. There was a moderate positive correlation between arterial and venous pH values for all patients (rs = 0.590, P < 0.001). There were a strong and very strong positive correlations between arterial and venous pCO2 and HCO3 values (rs = 0.725 and rs = 0.934, respectively) (P < 0.001). There was no correlation between arterial and venous pO2 and saturation values. There was an agreement in Bland–Altman method for the values of ABG and VBG (pH, pCO2, and HCO3).CONCLUSIONS:There was a correlation between ABG and VBG values (pH, pCO2, and HCO3). VBG parameters (pH, pCO2, and HCO3) can be used safely instead of ABG parameters which have many risks, during treatment and follow-up of patients with OHS and NMD.

Arterial PO2 Values Vary Dramatically During Diving and Surface Activities in the Freshwater Turtle (Trachemys scripta)

Mammals and birds maintain a narrow range of arterial PO2 values to preserve near complete O2 saturation. Since arterial blood gases in mammals and birds are tightly coupled with lung gas values, this is accomplished through changes in ventilation. In reptiles, pulmonary and system circulations are not completely separated and thus, cardiac shunts play a role in arterial blood gas values. Increases or decreases in the degree of right to left shunting (blood flow bypassing the pulmonary system) will immediately alter admixture and arterial PO2 can change rapidly despite stable ventilation. Further, anoxia‐tolerant reptiles, such as the red‐eared slider, may not need to maintain high arterial PO2 values. As a result, blood oxygen levels may vary more than in mammals and birds during diving as well as during other activities. To investigate this question, we continuously measured arterial PO2 in undisturbed, untethered red‐eared sliders (Trachemys scripta) over a 48‐hour period. Our hypotheses were (1) during routine activities, arterial PO2 values will vary but remain at or above 40 mmHg (75% O2 saturation) and (2) end of dive arterial PO2 values will be lower with longer submergences. Six adult red‐eared sliders (1546 ± 144g) were kept in tanks filled with 25°C water in a 25°C room. PO2 electrodes were surgically implanted in the carotid artery of anesthetized turtles. A self‐contained, waterproof data logger attached to the PO2 electrode was programmed to record PO2 at 1 Hz and epoxied to the carapace. After recovery, turtles were returned to the tank where they could freely swim and bask on a platform warmed by a heat lamp. Turtle behavior was recorded using a surveillance camera placed above the tank. Data were collected and analyzed. All procedures were approved by the University of California (IACUC #2011‐2995). Arterial PO2 during routine activities varied dramatically and individual PO2 values were often less than 40 mmHg. Mean PO2 values for each activity were: 22–42 mmHg for resting underwater; 23–55 mmHg while resting at surface; 29–49 mmHg during basking; and, 28–41 mmHg while swimming. Minimum PO2 values during surface events, basking, and swimming were often as low as minimum vales during submergences. End of submergence PO2 values varied dramatically from 2.7 to 51.7 mmHg and were significantly related to duration in only two turtles (p=0.007, 0.009). These results suggest freely diving, undisturbed T. scripta do not tightly regulate arterial O2 levels or maintain stable high arterial PO2 values even at the surface. The drive to maintain high arterial PO2 levels may be absent in these turtles due to their high tolerance to hypoxia and minimal metabolic demands.Support or Funding InformationThis research was funded by NSF IOS 1121324 (to J. Hicks). C.L.W. was supported in part by a National Institute of Health grant (NIH‐NIAMS T32AR047752 to V. Caiozzo).

Activity and biophysical inhibition resistance of a novel synthetic lung surfactant containing Super-Mini-B DATK peptide.

Background/objectives. This study examines the surface activity, resistance to biophysical inhibition, and pulmonary efficacy of a synthetic lung surfactant containing glycerophospholipids combined with Super Mini-B (S-MB) DATK, a novel and stable molecular mimic of lung surfactant protein (SP)-B. The objective of the work is to test whether S-MB DATK synthetic surfactant has favorable biophysical and physiological activity for future use in treating surfactant deficiency or dysfunction in lung disease or injury.Methods. The structure of S-MB DATK peptide was analyzed by homology modeling and by FTIR spectroscopy. The in vitro surface activity and inhibition resistance of synthetic S-MB DATK surfactant was assessed in the presence and absence of albumin, lysophosphatidylcholine (lyso-PC), and free fatty acids (palmitoleic and oleic acid). Adsorption and dynamic surface tension lowering were measured with a stirred subphase dish apparatus and a pulsating bubble surfactometer (20 cycles/min, 50% area compression, 37 °C). In vivo pulmonary activity of S-MB DATK surfactant was measured in ventilated rabbits with surfactant deficiency/dysfunction induced by repeated lung lavages that resulted in arterial PO2 values <100 mmHg.Results. S-MB DATK surfactant had very high surface activity in all assessments. The preparation adsorbed rapidly to surface pressures of 46–48 mN/m at 37 °C (low equilibrium surface tensions of 22–24 mN/m), and reduced surface tension to <1 mN/m under dynamic compression on the pulsating bubble surfactometer. S-MB DATK surfactant showed a significant ability to resist inhibition by serum albumin, C16:0 lyso-PC, and free fatty acids, but surfactant inhibition was mitigated by increasing surfactant concentration. S-MB DATK synthetic surfactant quickly improved arterial oxygenation and lung compliance after intratracheal instillation to ventilated rabbits with severe surfactant deficiency.Conclusions. S-MB DATK is an active mimic of native SP-B. Synthetic surfactants containing S-MB DATK (or related peptides) combined with lipids appear to have significant future potential for treating clinical states of surfactant deficiency or dysfunction, such as neonatal and acute respiratory distress syndromes.

Continuous arterial PO2profiles in unrestrained, undisturbed aquatic turtles during routine behaviors.

Mammals and birds maintain high arterial partial pressure of oxygen (PO2 ) values in order to preserve near-complete hemoglobin (Hb) oxygen (O2) saturation. In diving mammals and birds, arterial O2 follows a primarily monotonic decline and then recovers quickly after dives. In laboratory studies of submerged freshwater turtles, arterial O2 depletion typically follows a similar pattern. However, in these studies, turtles were disturbed, frequently tethered to external equipment and confined either to small tanks or breathing holes. Aquatic turtles can alter cardiac shunting patterns, which will affect arterial PO2 values. Consequently, little is known about arterial O2 regulation and use in undisturbed turtles. We conducted the first study to continuously measure arterial PO2 using implanted microelectrodes and a backpack logger in undisturbed red-eared sliders during routine activities. Arterial PO2 profiles during submergences varied dramatically, with no consistent patterns. Arterial PO2 was also lower than previously reported during all activities, with values rarely above 50 mmHg (85% Hb saturation). There was no difference in mean PO2 between five different activities: submerged resting, swimming, basking, resting at the surface and when a person was present. These results suggest significant cardiac shunting occurs during routine activities as well as submergences. However, the lack of relationship between PO2 and any activity suggests that cardiac shunts are not regulated to maintain high arterial PO2 values. These data support the idea that cardiac shunting is the passive by-product of regulation of vascular resistances by the autonomic nervous system.

Improved in vivo performance of amperometric oxygen (PO2) sensing catheters via electrochemical nitric oxide generation/release.

A novel electrochemically controlled release method for nitric oxide (NO) (based on electrochemical reduction of nitrite ions) is combined with an amperometric oxygen sensor within a dual lumen catheter configuration for the continuous in vivo sensing of the partial pressure of oxygen (PO2) in blood. The on-demand electrochemical NO generation/release method is shown to be fully compatible with amperometric PO2 sensing. The performance of the sensors is evaluated in rabbit veins and pig arteries for 7 and 21 h, respectively. Overall, the NO releasing sensors measure both venous and arterial PO2 values more accurately with an average deviation of −2 ± 11% and good correlation (R2 = 0.97) with in vitro blood measurements, whereas the corresponding control sensors without NO release show an average deviation of −31 ± 28% and poor correlation (R2 = 0.43) at time points >4 h after implantation in veins and >6 h in arteries. The NO releasing sensors induce less thrombus formation on the catheter surface in both veins and arteries (p < 0.05). This electrochemical NO generation/release method could offer a new and attractive means to improve the biocompatibility and performance of implantable chemical sensors.

Synthetic lung surfactant reduces alveolar-capillary protein leakage in surfactant-deficient rabbits

ABSTRACTPurpose of the Study: Alveolar-capillary leakage of proteinaceous fluid impairs alveolar ventilation and surfactant function and decreases lung compliance in acute lung injury. We investigated the correlation between lung function and total protein levels in bronchoalveolar lavage fluid (BALF) of ventilated, lavaged surfactant-deficient rabbits treated with various clinical and synthetic lung surfactant preparations. Materials and Methods: 109 ventilated, young adult New Zealand White rabbits underwent lung lavage to induce surfactant-deficiency (PaO2 <100 torr in 100% O2), were treated with a clinical surfactant or a synthetic surfactant preparation with surfactant protein B (SP-B) and/or surfactant protein C (SP-C) analogs, and mechanically ventilated for 120 min. Total protein levels in postmortem BALF were correlated with arterial PO2 (PaO2) and dynamic lung compliance values at 120 min post-surfactant treatment. Results: Repeated lung lavages decreased mean PaO2 values from 540 to 58 torr and lung compliance from 0.64 to 0.33 mL/kg/cm H2O. Two hours after surfactant therapy and mechanical ventilation, mean PaO2 values had increased to 346 torr and lung compliance to 0.44 mL/kg/cm H2O. Eighty-six rabbits (79%) responded to surfactant therapy with an increase in PaO2 to values >200 torr. Fourteen non-responders received inactive surfactant preparations. BALF protein levels were inversely correlated with PaO2 and lung compliance (P < .001). Surfactant preparations containing both SP-B and SP-C proteins or peptide analogs outperformed single protein/peptide preparations. Conclusions: Clinical and synthetic surfactant therapy reduces alveolar-capillary protein leakage in surfactant-deficient rabbits. Surfactant preparations with both SP-B and SP-C (analogs) were more efficient than preparations with SP-B or SP-C alone.

Time to Steady State after Changes in FIO2 in Patients with COPD

Background: International guidelines recommend that when changing FIO2 in patients with COPD receiving Long-Term Oxygen Therapy (LTOT), 30 minutes should be waited for steady state before measurement of arterial blood gasses. This study evaluates whether 30 minutes is really necessary, as a smaller duration might improve the logistics of care, potentially reducing the time spent by patients at the out-patient clinic. Methods: 12 patients with severe to very severe COPD according to the GOLD guidelines were included. Patients had a median FEV1% of 23% of the predicted value (range 15–64%), median FEV1/FVC 0.43 (range 0.26–0.63), and chronic respiratory failure necessitating LTOT, 1–4 liters/minute, minimum 16 hours/day. Following a FIO2 reduction (wash out), arterial blood gases were measured at 0, 1, 2, 4, 8, 12, 17, 22, 32 and 34 minutes. FIO2 was then increased to baseline levels (wash in) and blood gasses measured at 0, 1, 2, 4, 8, 12, 17, 22, 32, and 34 minutes. Data were analyzed to examine the dynamics of arterial PO2 and saturation (SO2) wash out and wash in by calculating the time constants, tau (ô), and to evaluate the time required to reach values which might be considered clinically stable, defined as PO2 within 0.5 kPa and SO2 within 1% of equilibrium values. Results: For arterial PO2 values of time constants were about 3 minutes and similar for both wash out and wash in. A median of 5 minutes was required to reach clinically stable values of PO2 in both wash out and wash in, with 7–8 minutes sufficient in 75% of patients, and in the worst case 14 minutes. For SO2, values of the time constant were 4.5 and 1.4 minutes for wash out and wash in, respectively. The time required to reach clinically stable values was different in the two phases. For wash out the median time was 7.4 minutes, and in the worst case 15.6 minutes. For wash in the median time was 2.6 minutes and in worst case 6.8 minutes. No significant changes in PCO2 or pH were seen during FIO2 changes. Discussion/Conclusion: This study shows that oxygen equilibration relevant for clinical interpretation requires only 10 minutes following an increase and 16 minutes following a decrease in FIO2. over the range studied.

Mathematical arterialization of venous blood in emergency medicine patients

Arterial punctures represent a painful and unpleasant experience. Acid-base and oxygenation status can be assessed from peripheral venous blood, but agreement with arterial values is not always clinically acceptable. This study evaluates a method for mathematically transforming peripheral venous values into arterial values in emergency medicine patients. Paired arterial and peripheral venous samples were analysed in groups A (47 patients) and B (101 patients), corresponding to the clinical need for arterial blood sampling (A) and without (B). Venous values were input into the mathematical arterialization method and the values of arterial pH, PCO2 and PO2 were calculated and compared with the measured values. The calculated and measured arterial pH and PCO2 values correlated well with the correlation coefficients (r ) of group A, pH 0.94, PCO2 0.97; group B, pH 0.87, PCO2 0.83; and Bland-Altman limits of agreement well within the limits of acceptable laboratory and clinical performance. The calculated values of arterial PO2 followed a set of predefined rules relating calculated and measured PO2 levels in all cases. The method represents an improvement on the use of venous blood alone where the correlation coefficients were as follows: group A, pH 0.85, PCO2 0.88; group B, pH 0.79, PCO2 0.59; and limits of agreement for PCO2 at the border of (group A) or beyond (group B) acceptable clinical limits. Application of the mathematical arterialization method may reduce the pain associated with assessment of acid-base and oxygenation status, maximize the information obtained from peripheral venous blood and allow venous measurements to be presented as more commonly interpreted arterial values.

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Introduction: Blood gas analysis is often used to evaluate oxygenation status in critically ill patients. Although arterial blood gas (ABG) remains the gold standard, pulse oximetry (SpO2) is non-invasive and more readily available. Hypothesis: The purpose of this study was to evaluate the correlation of SpO2 and arterial pO2. We hypothesized that SpO2 would correlate with arterial pO2 as predicted by the standard oxygen-hemoglobin dissociation curve. Methods: We performed a prospective cohort study of patients in the emergency department (ED) and intensive care unit (ICU) at a single academic tertiary referral center. Patients were eligible for enrollment if the treating physician ordered an ABG. SpO2 and arterial pO2 were analyzed using paired t-test, Pearson’s chi-square and Pearson’s correlation. Results: There were 156 patients enrolled and 129 patients completed the study. Of the patients completing the study, 53 (41.1%) were in the ED, 41 (31.8%) were in the medical ICU and 35 (27.1%) were in the surgical ICU. There were 123 (95.3%) patients with SpO2 >90%. Of these patients, 116 (94.3%) had SpO2 >90% and arterial pO2 >60 mmHg, 7 (5.7%) had SpO2 >90% and arterial pO2 <60 mmHg. Of these 7 patients, 5 were alkalemic (pH=7.44, 7.44, 7.46, 7.46, 7.52), 1 patient had a neutral pH (pH=7.40) and 1 patient was acidemic (pH=7.25). Conclusions: SpO2 correlated well with arterial pO2 as predicted by the standard oxygen-hemoglobin dissociation curve in a undifferentiated critically ill patient population. In this study, a SpO2 >90% correlated with an arterial pO2 >60 mmHg more than 94% of the time. As alkalemia shifts the standard oxygen-hemoglobin dissociation curve to the left it may cause SpO2 values >90% despite arterial pO2 values <60 mmHg. This shift in the standard oxygen-hemoglobin dissociation curve may be clinically significant and should be considered when interpreting SpO2 in the setting of alkalemia.

Methodologies for studying peripheral O2 chemosensing: Past, present, and future

The reduction of molecular oxygen in individual cells during the process of oxidative phosphorylation is central to oxidative metabolism and bioenergetic homeostasis. As such, any insufficiency in molecular oxygen availability represents a severe threat to sustained life. Thus, as with other similar multicellular organisms, the human body has evolved various peripheral chemosensory pathways that play a key role in sampling arterial PO₂ values and initiating corrective reflex responses so as to maintain homeostasis. Research on these peripheral chemosensors can trace their origins to the cross circulation studies of Corneille Heymans in the early 20th century. Since then, it has become increasingly apparent that defects in these chemosensory pathways play a key role in various pathological conditions, e.g. Sudden Infant Death Syndrome (SIDS), and therefore an understanding of the underlying mechanisms is of critical importance. This review aims to discuss the advantages and disadvantages of the various experimental models employed in studying the mechanisms by which acute peripheral chemosensing occurs.

Respiratory muscle training and maximum aerobic power in hypoxia

In a recent paper, Keramidas et al. (2010) investigated the effects of respiratory muscle training (RMT) on endurance exercise performance in normoxia (N) and hypoxia (H; FIO2 = 0.12). Participants were randomly assigned either to RMT or control training group. Both groups performed regular (1 h/day, 5 days/week at 50% of peak power output) aerobic training on a cycle ergometer, while RMT group performed an additional specific training programme of respiratory muscles (isocapnic hyperpnoea) prior to the cycle ergometry. After 4 weeks of training, both groups enhanced maximum oxygen uptake _ VO2max in N, but only the RMT group improved _ VO2max (only specific, not absolute) significantly in H. The enhanced _ VO2max in H in the RMT group was accompanied by increased maximum ventilation _ VE , but at an identical peak power output, most likely resulting in an increased metabolic demand of the respiratory muscles. However, in this study, peak power output was calculated as the last workload completed of a ramp test (30 W/min). If this is the case, peak power output would be a supramaximal power, which both aerobic and anaerobic energy sources would contribute to, and thus cannot be defined as the maximum aerobic mechanical power, which corresponds to the lowest power requiring a _ VO2 equal to _ VO2max. Always, whether in N or in H, an increase in _ VO2max is accompanied by an increase in maximum mechanical power. In a similar paper, Esposito et al. (2010) assessed the effects of 8 weeks RMT (isocapnic hyperpnoea, 5 training sessions per week, 10–20 min each including warm up; the volume and the frequency of respiratory cycles were increased progressively, based on participants’ response to training work loads) on _ VO2max in N and H (FIO2 = 0.11). After 8 weeks of RMT, no changes in cardiorespiratory and metabolic variables were detected at maximal exercise in N. On the contrary, in H _ VE and alveolar ventilation _ VA at maximal exercise were significantly higher than in pre-training condition. Accordingly, alveolar O2 partial pressure (PAO2 ) after RMT significantly increased by *10%. Nevertheless, arterial PO2 and _ VO2max did not change with respect to pre-training condition. Thus, the authors provided evidence that RMT did not have any effect on _ VO2max, under either normoxic or hypoxic condition. They concluded that in H, the significant increase in _ VE and _ VA at maximum exercise after RMT lead to higher alveolar but not arterial PO2 values, revealing an increased A–a gradient. Thus, a possible role of increased ventilation–perfusion mismatch was suggested. According to multifactorial models of _ VO2max limitation (di Prampero 1985; di Prampero and Ferretti 1990), the O2 transfer from ambient air to mitochondria is set by a cascade of resistances in series, each resistance being overcome by a specific O2 partial pressure gradient. Four major resistances have been identified in the studies cited above (1) ventilatory (RV) between ambient and alveoli; (2) lung (RL) between alveoli and arterial blood; (3) circulatory (RQ) between arterial blood and muscle capillaries; (4) peripheral (Rp) between muscle capillaries and Communicated by Susan Ward.

Effect of respiratory muscle training on maximum aerobic power in normoxia and hypoxia

To assess the effects of respiratory muscle training (RMT) on maximum oxygen uptake (VO2max) in normoxia and hypoxia, 9 healthy males (age 24 +/- 4 years; stature 1.75 +/- 0.08 m; body mass 72 +/- 9 kg; mean +/- SD) performed on different days maximal incremental tests on a cycle ergometer in normoxia and normobaric hypoxia (FIO2=0.11), before and after 8 weeks of RMT (5 days/week). During each test, gas exchange variables were measured breath-by-breath by a metabolimeter. After RMT, no changes in cardiorespiratory and metabolic variables were detected at maximal exercise in normoxia. On the contrary, in hypoxia expired and alveolar ventilation (V(E(and V(A), respectively) at maximal exercise were significantly higher than pre-training condition (+12 and +13%, respectively; P < 0.05). Accordingly, alveolar O2 partial pressure (PAO2) after RMT significantly increased by approximately 10%. Nevertheless, arterial PO2 and VO2max did not change with respect to pre-training condition. In conclusion, RMT improved respiratory function but did not have any effect on VO2max, neither under normoxic nor hypoxic condition. In hypoxia, the significant increase in V(E) and V(A) at maximum exercise after training lead to higher alveolar but not arterial PO2 values, revealing an increased A-a gradient. This result, according to the theoretical models of VO2max limitation, seems to contradict the lack of VO2max increase in hypoxia, suggesting a possible role of increased ventilation-perfusion mismatch.

Direct measurement of myocardial oxygen tension and high energy phosphate content under varying ventilatory conditions in rabbits / Messung von myokardialem Sauerstoffpartialdruck und energiereichen Phosphaten unter verschiedenen Beatmungsbedingungen beim Kaninchen

Effective myocardial oxygen supply should not be compromised during cardiac surgery as it is essential to avoid circulatory and cardiac dysfunction. Local measurement of myocardial oxygen partial pressure (pO2) was therefore introduced into the operative monitoring of myocardial ischemia. The aim of the present study was to assess whether myocardial oxygen partial pressure correlates with the content of high energy phosphates (HEPs). Seven male rabbits were examined in parallel with measurement of myocardial pO2 by an implanted Clark electrode and 31phosphorus-NMR spectroscopy. The ventilatory management established hyperoxygenation followed by systemic hypoxia with hypercapnia for 20 min. Additionally, analysis of end-expiratory gas composition in combination with blood gas analysis was performed simultaneously, and hemodynamic parameter was recorded. Under hypoxic conditions the cardiovascular system was severely compromised, whereas the myocardial pO2 was only moderately impaired (pO2M 45.0+/-16.0 mm Hg). Immediately before cardiac arrest, low values of arterial and venous pO2 were found (17.6+/-6.0 and 12.9+/-6.1 mm Hg). In contrast to near normal myocardial pO2, HEP content in the myocardium was considerably reduced and inorganic phosphorus was increased. Artificial ventilation leading to systemic hypoxia and eventually circulatory arrest resulted in almost normal myocardial pO2 but severely compromised HEP content. This somewhat unexpected finding requires further clarification, but is in accordance with findings reported previously where regulatory mechanisms have been shown to play a role in the pathophysiology of severe hypoxic conditions such as those for cellular oxygen delivery and demand, P/O coupling and finally control of HEP production facilitating the interaction between respiratory chain and myoglobin oxygen transport.

O2 store management in diving emperor penguins

In order to further define O(2) store utilization during dives and understand the physiological basis of the aerobic dive limit (ADL, dive duration associated with the onset of post-dive blood lactate accumulation), emperor penguins (Aptenodytes forsteri) were equipped with either a blood partial pressure of oxygen (P(O(2))) recorder or a blood sampler while they were diving at an isolated dive hole in the sea ice of McMurdo Sound, Antarctica. Arterial P(O(2)) profiles (57 dives) revealed that (a) pre-dive P(O(2)) was greater than that at rest, (b) P(O(2)) transiently increased during descent and (c) post-dive P(O(2)) reached that at rest in 1.92+/-1.89 min (N=53). Venous P(O(2)) profiles (130 dives) revealed that (a) pre-dive venous P(O(2)) was greater than that at rest prior to 61% of dives, (b) in 90% of dives venous P(O(2)) transiently increased with a mean maximum P(O(2)) of 53+/-18 mmHg and a mean increase in P(O(2)) of 11+/-12 mmHg, (c) in 78% of dives, this peak venous P(O(2)) occurred within the first 3 min, and (d) post-dive venous P(O(2)) reached that at rest within 2.23+/-2.64 min (N=84). Arterial and venous P(O(2)) values in blood samples collected 1-3 min into dives were greater than or near to the respective values at rest. Blood lactate concentration was less than 2 mmol l(-1) as far as 10.5 min into dives, well beyond the known ADL of 5.6 min. Mean arterial and venous P(N(2)) of samples collected at 20-37 m depth were 2.5 times those at the surface, both being 2.1+/-0.7 atmospheres absolute (ATA; N=3 each), and were not significantly different. These findings are consistent with the maintenance of gas exchange during dives (elevated arterial and venous P(O(2)) and P(N(2)) during dives), muscle ischemia during dives (elevated venous P(O(2)), lack of lactate washout into blood during dives), and arterio-venous shunting of blood both during the surface period (venous P(O(2)) greater than that at rest) and during dives (arterialized venous P(O(2)) values during descent, equivalent arterial and venous P(N(2)) values during dives). These three physiological processes contribute to the transfer of the large respiratory O(2) store to the blood during the dive, isolation of muscle metabolism from the circulation during the dive, a decreased rate of blood O(2) depletion during dives, and optimized loading of O(2) stores both before and after dives. The lack of blood O(2) depletion and blood lactate elevation during dives beyond the ADL suggests that active locomotory muscle is the site of tissue lactate accumulation that results in post-dive blood lactate elevation in dives beyond the ADL.

Mitigation of chlorine-induced lung injury by low-molecular-weight antioxidants

Chlorine (Cl(2)) is a highly reactive oxidant gas used extensively in a number of industrial processes. Exposure to high concentrations of Cl(2) results in acute lung injury that may either resolve spontaneously or progress to acute respiratory failure. Presently, the pathophysiological sequelae associated with Cl(2)-induced acute lung injury in conscious animals, as well as the cellular and biochemical mechanisms involved, have not been elucidated. We exposed conscious Sprague-Dawley rats to Cl(2) gas (184 or 400 ppm) for 30 min in environmental chambers and then returned them to room air. At 1 h after exposure, rats showed evidence of arterial hypoxemia, respiratory acidosis, increased levels of albumin, IgG, and IgM in bronchoalveolar lavage fluid (BALF), increased BALF surfactant surface tension, and significant histological injury to airway and alveolar epithelia. These changes were more pronounced in the 400-ppm-exposed rats. Concomitant decreases of ascorbate (AA) and reduced glutathione (GSH) were also detected in both BALF and lung tissues. In contrast, heart tissue AA and GSH content remained unchanged. These abnormalities persisted 24 h after exposure in rats exposed to 400 ppm Cl(2). Rats injected systemically with a mixture of AA, deferoxamine, and N-acetyl-L-cysteine before exposure to 184 ppm Cl(2) had normal levels of AA, lower levels of BALF albumin and normal arterial Po(2) and Pco(2) values. These findings suggest that Cl(2) inhalation damages both airway and alveolar epithelial tissues and that resulting effects were ameliorated by prophylactic administration of low-molecular-weight antioxidants.

Blood oxygen depletion during rest-associated apneas of northern elephant seals (Mirounga angustirostris)

Blood gases (P(O)2, P(CO)2, pH), oxygen content, hematocrit and hemoglobin concentration were measured during rest-associated apneas of nine juvenile northern elephant seals. In conjunction with blood volume determinations, these data were used to determine total blood oxygen stores, the rate and magnitude of blood O(2) depletion, the contribution of the blood O(2) store to apneic metabolic rate, and the degree of hypoxemia that occurs during these breath-holds. Mean body mass was 66+/-9.7 kg (+/- s.d.); blood volume was 196+/-20 ml kg(-1); and hemoglobin concentration was 23.5+/-1.5 g dl(-1). Rest apneas ranged in duration from 3.1 to 10.9 min. Arterial P(O)2 declined exponentially during apnea, ranging between a maximum of 108 mmHg and a minimum of 18 mmHg after a 9.1 min breath-hold. Venous P(O)2 values were indistinguishable from arterial values after the first minute of apnea; the lowest venous P(O)2 recorded was 15 mmHg after a 7.8 min apnea. O(2) contents were also similar between the arterial and venous systems, declining linearly at rates of 2.3 and 2.0 ml O(2) dl(-1) min(-1), respectively, from mean initial values of 27.2 and 26.0 ml O(2) dl(-1). These blood O(2) depletion rates are approximately twice the reported values during forced submersion and are consistent with maintenance of previously measured high cardiac outputs during rest-associated breath-holds. During a typical 7-min apnea, seals consumed, on average, 56% of the initial blood O(2) store of 52 ml O(2) kg(-1); this contributed 4.2 ml O(2) kg(-1) min(-1) to total body metabolic rate during the breath-hold. Extreme hypoxemic tolerance in these seals was demonstrated by arterial P(O)2 values during late apnea that were less than human thresholds for shallow-water blackout. Despite such low P(O)2s, there was no evidence of significant anaerobic metabolism, as changes in blood pH were minimal and attributable to increased P(CO)2. These findings and the previously reported lack of lactate accumulation during these breath-holds are consistent with the maintenance of aerobic metabolism even at low oxygen tensions during rest-associated apneas. Such hypoxemic tolerance is necessary in order to allow dissociation of O(2) from hemoglobin and provide effective utilization of the blood O(2) store.

Alveolar recruitment versus hyperinflation: a balancing act

To address lung recruitment according to pressure/volume curves, along with regional recruitment versus hyperinflation evidence from computed tomography and electrical impedance tomography. Cyclical tidal volume recruitment of atelectatic lung regions causes acute lung injury, as do large breaths during pneumonectomy. Using the lower inflection point on the static pressure/volume inflation curve plus 2 cmH2O as a positive end-expiratory pressure setting limits hyperinflation in acute lung injury, but may not provide enough positive end-expiratory pressure to avoid cyclical recruitment/derecruitment injury in more severe acute lung injury regions. Both computed tomography and electrical impedance tomography can help titrate positive end-expiratory pressure in these regions, thereby assuring an 'open lung' ventilatory pattern. Regional pressure/volume curves show that adequate positive end-expiratory pressure for severe acute lung injury regions may not be reliably determined from whole lung pressure/volume curves. Balancing positive end-expiratory pressure requires both arterial PO2 and PCO2 values to determine at what level hyperinflated regions become seriously underperfused (develop very high ventilation-perfusion ratios), adding to the hypercarbia from increased deadspace. Positive end-expiratory pressure levels must be high enough to minimize recruitment/derecruitment cycling. Balancing recruitment versus overdistension may require thoracic tomography, to assure sufficient improvement in oxygenation while limiting hypercarbia.