Arterial PCO2 Research Articles

Interactions between arousal state and CO₂ determine the activity of central chemoreceptor neurons that drive breathing.

The homeostatic regulation of pulmonary ventilation, and ultimately arterial PCO2, depends on interactions between respiratory chemoreflexes and arousal state. The ventilatory response to CO2 is triggered by neurons in the retrotrapezoid nucleus (RTN) that function as sensors of central pH, which can be identified in adulthood by expression of Phox2b and Neuromedin B. Here we examine the dynamic response of genetically-defined RTN neurons to hypercapnia and arousal state in freely-behaving adult male and female mice using the calcium indicator jGCaMP7 and fiber photometry. We found that hypercapnia vigorously activates RTN neurons with a low CO2 recruitment threshold and with response kinetics that match respiratory activity whereas hypoxia had little effect. RTN activity increased transiently during wakefulness and respiratory-related arousals, rose persistently during REM sleep and their CO2 response persisted under anesthesia. Complementary studies using inhibitory optogenetics show that RTN activity supports eupneic breathing under anesthesia as well as during states of high arousal, but their activity is redundant for voluntary breathing patterns. Collectively, this study demonstrates that CO2-activated RTN neurons are exquisitely sensitive to arousal state, which determines their contribution to alveolar ventilation in relation to arterial PCO2 Significance statement Respiratory chemoreceptors stimulate neural respiratory motor output to regulate arterial PCO2 and PO2, thereby maintaining optimal gas exchange. Central chemoreceptor neurons expressing Phox2b and Neuromedin B in the Retrotrapezoid Nucleus (RTN) are required for the hypercapnia ventilatory response. However, the dynamic activity of RTN neurons in conditions of normal and elevated carbon dioxide has not been described in unanesthetized conditions. Here, we use a genetically-encoded calcium indicator to demonstrate that RTN neurons exquisitely sensitivity to hypercapnia and variations in arousal and sleep-state in freely-behaving mice. This work has implications for understanding the central control of breathing across arousal-states, particularly during sleep and anesthesia.

Mixed venous to arterial pCO2-gap is poorly correlated to cardiac index in 1526 pulmonary artery catheter monitored critically ill patients

Abstract Background The CO2 gap is the difference between mixed venous and arterial CO2, and can be estimated by the difference in partial pressure in CO2 (Pv-aCO2 or ∆PCO2). ∆PCO2 is affected by cardiac output (CO), CO2 production and solubility. The central venous-to-arterial CO2 gap has been proposed as a less invasive surrogate for P(v-a)CO2 and has been investigated as a measure of adequacy of resuscitation, and to guide sepsis management. Nevertheless, the CO2-gap as determinant of CO has never been thoroughly investigated in large cohort of critically ill ICU-patients. This study aims to investigate the relationship between ∆PCO2 and cardiac index (CI) in a retrospective cohort of critically ill patients in a large quaternary cardiothoracic intensive care unit. Methods Over 62 months, pulmonary artery catheter monitored critically ill patients were identified and their case files reviewed in retrospect. Extracorporeal membrane oxygenation (ECMO) patients were excluded. P(v-a)CO2 measurements were defined as mixed venous and arterial pCO2 measurements drawn simultaneously or within maximum 30 minutes together with PA-measurements. Correlation coefficients were calculated between P(v-a)CO2 and CI, serum lactate, mixed venous saturations (SvO2), cardiac power index (CPI), inotropic score (IS), central venous pressure (CVP) and minute expiratory volume (MV)(Table 1). We used receiver operator characteristic (ROC) curves to assess the diagnostic performance of P(v-a)CO2 as a surrogate for CI lower than 2,2L/min/m2. Multivariate linear regression analysis was performed with P(v-a)CO2 as an dependent variable. Results 4414 P(v-a)CO2 measurements were identified from 1526 patients. Median P(v-a)CO2 was 0,86 kPa (0,66-1,1) or 6.45 mmHg (4.95-8.25), and mean CI was 2.7l/min/m2 (2.2-3.2). Correlation coefficients of P(v-a)CO2 with the other variables remained poor (> 0,35). The area under the ROC curve for P(v-a)CO2 as a predictor of CI<2.2l/min/m2 was 0.65, p<0.0001 (Fig. 1B). A value of P(v-a)CO2 > 6.9 mmHg was found to have the highest sensitivity and specificity, with a poor performance of 61.21% sensitivity and 62.73% specificity. Conclusion This large retrospective study in 1526 critically ill cardiac ICU-patients did not demonstrate a strong relationship between P(v-a)CO2 and CI, nor with any other hemodynamic variable found in the ICU patient cohort studied (Table 1). This raises scepticism regarding the efficacy of P(v-a)CO2 as a physiological goal in guiding resuscitation and management of this precarious patient group. Therefore, we argue that the PA-catheter remains the cornerstone in assessing critically ill (cardiothoracic) ICU patients.

There is no limitation for CO2 excretion across the lung in exercising American alligators (Alligator mississippiensis).

Vertebrates utilize various respiratory organs like gills, lungs, and skin in combination with diverse cardiovascular structures, including single, three, and four-chambered hearts, to enable oxygen delivery and carbon dioxide removal. They also exhibit differences in aerobic and anaerobic metabolism during exertion, but the cardiorespiratory gas transport of all vertebrates follow is a similar a four-step process governed by Fick's Principle and Fick's Law of Diffusion over the entire range of metabolic rates. Hillman et al. (2013) suggested that previous exercise studies have focused too narrowly on mammals and proposed that the cardiorespiratory system's excess capacity serves an evolutionary role in enhancing CO2 excretion in non-mammalian vertebrates. In contrast, an analysis by Hicks and Wang (2021) concluded that vertebrates maintain effective gas exchange even at peak activity, finding no evidence of arterial hypercapnia at maximal oxygen consumption and thus challenging the proposal of significant limitations to pulmonary or branchial CO2 efflux. In the present study, we investigate the limits for CO2 exchange in exercising American alligators (Alligator mississippiensis) and provide evidence that the cardiorespiratory system is adequately built to sustain CO2 excretion during strenuous exercise and maintain arterial PCO2 , with no evidence of diffusion limitation for pulmonary CO2 excretion.

Temperature effects on blood gases in embryonic American alligators (Alligator mississippiensis)

Numerous studies report on the influence of temperature on blood gases in ectothermic vertebrates, but there is merely a cursory understanding of these effects in developing animals. Animals that develop in eggs are at the mercy of environmental temperature and are expected to lack the capacity to regulate gas exchange and may regulate blood gases by means of altered conductance for gas exchange. We, therefore, devised a series of studies to characterize the developmental changes in blood gases when embryonic alligators were exposed to 25, 30 and 35 °C. To determine how blood parameters were impacted by changes in embryonic temperature, blood was sampled from the chorioallantoic membrane artery. The blood in the chorioallantoic membrane artery is a mixture of oxygen-poor and oxygen-rich blood, which based on the embryonic vascular anatomy may reflect blood that perfuses the chemoreceptors of the developing animal. Our findings indicate that following a 48 h exposure to 25 °C or 35 °C, there was a positive relationship between CAM artery blood PO2, PCO2 and glucose. However, blood pH suggests embryonic alligators lack an acute regulatory mechanism for adjusting blood pH.

A Systematic Review and Meta-Analysis of Physiologic Variables in Sheep Fetuses.

The fetal sheep model has been widely used in fetal therapy research. However, there is a significant degree of variability among published normal values. Our study aimed to evaluate the literature available on normal values for hemodynamics, blood gases, and acid-base status in the sheep fetus and to determine the best possible estimation of such physiologic values. We conducted a systematic review with a comprehensive search of several databases. We included 189 articles in the database and over 2,800 sheep fetuses. Analysis revealed a mean umbilical blood flow of 202 mL/kg/min (95% CI: 182 to 223); mean arterial pCO₂ of 49.8 mm Hg (95% CI: 49.2 to 50.3); mean arterial pO₂ of 22.3 mm Hg (95% CI: 21.9 to 22.7); mean arterial pH of 7.35 (95% CI: 7.3487 to 7.3562); and mean arterial oxygen saturation of 59.8 (95% CI; 58 to 61.7). Our findings were punctuated by a high heterogeneity, for which we conducted several subanalyses. The results showed high heterogeneity and small study effect in the literature available and provided our best assessment of relevant variables on normal hemodynamics, blood gases, and acid-base status in the fetus after using strategies to mitigate the risk of bias present in the literature.

Cerebrospinal fluid pressure dynamics across the intra- and postoperative setting: Retrospective study of a spine surgery cohort

Timely and sufficient decompression are critical objectives in degenerative cervical myelopathy (DCM) and spinal cord injury (SCI). We previously investigated intraoperative cerebrospinal fluid pressure (CSFP) for determining surgical outcomes. However, confounding factors during the intra- and postoperative setting need consideration. These are related to type of respiration (i.e., artificial vs. natural) and anesthesia, which affect CSFP dynamics through the interaction between the cardiorespiratory system and the CSF compartment. This retrospective cohort study (NCT02170155) aims to systematically investigate these factors to facilitate CSFP interpretation. CSFP was continuously measured through a lumbar catheter, intra- and postoperatively, in 21 patients with DCM undergoing decompression surgery. Mean CSFP and cardiac-driven CSFP peak-to-valley amplitude (CSFPp) were analyzed throughout the perioperative period, including the immediate extubation period in eight patients. Intraoperative mean CSFP had a median value and {interquartile range} of 10.8 {5.5} mmHg and increased 1.6-fold to 16.9 {7.1} mmHg postoperatively (p < 0.001). CSFPp increased 3-fold from 0.6 {0.7} to 1.8 {2.5} mmHg (p = 0.001). Increased CSFP persisted overnight. During extubation, there was a notable increase in CSFP and CSFPp of 14.0 {5.8} and 5.1 {3.1} mmHg, respectively. From case-based analysis, this was attributed to an arterial pCO2 increase. There was no correlation between respirator settings and CSFP metrics. There were distinct and quantifiable changes in CSFP dynamics from the intra- to postoperative setting related to type of respiration, anesthesia, and level of consciousness. When monitoring CSFP dynamics in spine surgery across these settings, cardiorespiratory factors must be controlled for.

Intrinsic molecular proton sensitivity underlies GPR4 effects on retrotrapezoid nucleus (RTN) neuronal activation and CO2-stimulated breathing.

An interoceptive homeostatic reflex monitors levels of CO2/H+ to maintain blood gas homeostasis and rapidly regulate tissue acid-base balance by driving lung ventilation and CO2 excretion - this CO2-evoked increase in respiration is the hypercapnic ventilatory reflex (HCVR). Retrotrapezoid nucleus (RTN) neurons provide crucial excitatory drive to downstream respiratory rhythm/pattern-generating circuits, and their activity is directly modulated by changes in CO2/H+ RTN neurons express GPR4 and TASK-2, global deletion of which abrogates CO2/H+ activation of RTN neurons and the HCVR. It has not been determined if the intrinsic pH sensitivity of these proton detectors is required for these effects. We used CRISPR/Cas9 genome editing to generate mice with mutations in either of two pH-sensing histidine residues in GPR4 to determine effects on RTN neuronal CO2/H+ sensitivity and the HCVR. In global GPR4(H81F) and GPR4(H167F) mice, CO2-stimulated breathing and CO2-induced RTN neuronal activation were strongly blunted, with no effect on hypoxia-stimulated breathing. In brainstem slices from GPR4(H81F) mice, peak firing of RTN neurons during bath acidification was significantly reduced compared to GPR4 wild type mice, and a subpopulation of RTN neurons was rendered pH-insensitive, phenocopying previous results from GPR4-deleted mice. These effects were independent of changes in RTN number/distribution, neuronal excitability or transcript levels for GPR4 and TASK-2. CO2-stimulated breathing was reduced to a similar extent in GPR4(H81F) and TASK-2-deleted mice, with combined mutation yielding no additional deficit in the HCVR. Together, these data demonstrate that the intrinsic pH sensitivity of GPR4 is necessary for full elaboration of the HCVR.Significance Statement Among the critical mechanisms for whole-body homeostasis, the hypercapnic ventilatory reflex (HCVR) regulates lung ventilation in order to maintain physiological levels of arterial PCO2 and acid-base balance. GPR4 is a proton-activated receptor and putative molecular proton sensor in retrotrapezoid nucleus (RTN) neurons, which are a crucial neural component of this respiratory reflex. In this work, we developed multiple lines of mice in which the intrinsic pH sensitivity of GPR4 was globally disabled by mutations in key histidine residues; in those mice, CO2/H+-sensitivity of RTN neurons and the HCVR were strongly blunted. These data support a role for GPR4 as a direct molecular sensor for CO2/H+ in support of this important homeostatic reflex.

Correlation of arterial and venous blood gas analysis in respiratory failure in children

IntroductionArterial and venous blood gases provide similar and very close measurements in terms of PH, pCO2, HCO3, pO2 levels. The study aims to investigate correlation of arterial and venous blood gas analysis in respiratory failure caused by pneumonia in children.MethodsThis cross-sectional study employed a consecutive sampling method from pediatric patients experiencing respiratory failure. Point of Care (POCT) was used to examine blood gas analysis.ResultThere was no significant difference between pH artery and venous with p = 0,232 (95% confidence interval [CI]: -14.628-59,488). The Mean difference between arterial and venous pH was 0,22 with a strong Spearman correlation of 0,643 (p < 0,001). There was a significant difference between arterial and venous pCO2 with p = 0,022 (95% confidence interval [CI]: -8,7- (− 0,69)). The mean difference between arterial and venous pCO2 was 4,69 with a moderate Spearman correlation of 0,485 (p < 0,001). There was no significant difference between arterial and venous HCO3 with p = 0,38. The Mean difference between arterial and venous HCO3 was 3,1 with a very strong Spearman correlation of 0,848 (p < 0,001). There was a very significant difference between arterial and venous pO2 with p < 0,001. The Mean difference between arterial and venous pO2 was 27,4 with a weak Spearman correlation of 0,17 (p = 0,117).ConclusionThere was strong correlation between arterial and venous pH, a moderate correlation between arterial and venous pCO2, a very strong correlation between arterial and venous HCO3 and a very weak correlation between arterial and venous pO2 using POCT.

The Effect of Hypertonic Saline Nebulization on Arterial Blood Gas Parameters Among Patients on a Mechanical Ventilator.

Introduction Care of the airway is an essential part of the management of patients receiving mechanical ventilation. If the airway is not properly managed, an endotracheal airway can result in retained secretions, airway obstructions, and infections. These complications may prolong mechanical ventilation durationand length of hospital stayand may increase the cost of affordability. Hypertonic saline nebulized suctioning is a technique used to lessen the duration of mechanical air flow and enhance airway clearance, which helps patients on mechanical ventilation breathe easier. Aim The objective of the study isto assess the effectiveness of nebulization with hypertonic saline on arterial blood gas parameters among mechanically ventilated patients. Methods The quasi-experimental design adopted with thirty-five mechanically ventilated samples was chosen using a non-probability purposive sample technique. Following the pre-test in the endotracheal tube, nebulization was given with 2 ml of hypertonic saline over 15-20 mins, two times each day, to the mechanically ventilated patients. Post-test was carried out about 15-20 minutes after the procedureusing arterial blood gas analysis results were obtained and interpreted. Results The study reveals that the p values corresponding to the arterial blood gas parameters PCo2, pO2, and HCo3 are less than 0.01 and are significant at a 1% level, and arterial blood gas(ABG) pHis less than 0.05 and is significant at a 5% level; hence there is a high significant difference between the pre-test and post-test mean scores of arterial blood gas parameters PCo2, pO2, HCo3, and ABG pH. Hence, the study concluded that nebulization with hypertonic saline for patients with mechanical ventilators is more effective in improving arterial blood gas parameters.

Impact of procedural handling on the physiological effects of alfaxalone anaesthesia in the ball python (Python regius)

To describe the cardiovascular changes following intramuscular (handled) and intravascular (undisturbed, via intraarterial catheter) alfaxalone administration, we studied 20 healthy ball pythons (Python regius) in a randomised, prospective study. The pythons were instrumented with occlusive arterial catheters to facilitate undisturbed, continuous monitoring of heart rate and blood pressure. Six pythons were administered intramuscular (IM) saline, followed by 20 mg/kg IM alfaxalone, and were manually restrained for both injections. Six pythons received intraarterial (IA) saline, followed by 10 mg/kg IA alfaxalone, and remained undisturbed for both injections. Arterial blood samples were taken at 0, 12 and 60 min post-injection, and heart rate and blood pressure were recorded for 60 min. The remaining eight snakes received 20 mg/kg IM or 10 mg/kg IA alfaxalone (n = 4 per treatment) and were not handled for intubation 10 min post-injection, to examine the effects of handling during anaesthesia. IM administration of 20 mg/kg alfaxalone or an equivalent volume of saline elicited a profound tachycardia and hypertension, which recovered to resting values after 20 min. However, when 10 mg/kg alfaxalone or saline were injected IA, mild hypotension and a lower magnitude tachycardia occurred. Arterial PCO2 and PO2, pH and lactate concentrations did not change following IA alfaxalone, but an acidosis was observed during IM alfaxalone anaesthesia. There were no significant changes in plasma catecholamines and corticosterone among treatments. Handling for injection and during anaesthesia associated with intubation significantly affects cardiovascular parameters, whereas alfaxalone per se only elicits minor changes in cardiovascular physiology.

Evidence for direct CO2 -mediated alterations in cerebral oxidative metabolism in humans.

How the cerebral metabolic rates of oxygen and glucose utilization (CMRO2 and CMRGlc, respectively) are affected by alterations in arterial PCO2 (PaCO2) is equivocal and therefore was the primary question of this study. This retrospective analysis involved pooled data from four separate studies, involving 41 healthy adults (35 males/6 females). Participants completed stepwise steady-state alterations in PaCO2 ranging between 30 and 60 mmHg. The CMRO2 and CMRGlc were assessed via the Fick approach (CBF × arterial-internal jugular venous difference of oxygen or glucose content, respectively) utilizing duplex ultrasound of the internal carotid artery and vertebral artery to calculate cerebral blood flow (CBF). The CMRO2 was altered by 0.5 mL × min-1 (95% CI: -0.6 to -0.3) per mmHg change in PaCO2 (p < 0.001) which corresponded to a 9.8% (95% CI: -13.2 to -6.5) change in CMRO2 with a 9 mmHg change in PaCO2 (inclusive of hypo- and hypercapnia). The CMRGlc was reduced by 7.7% (95% CI: -15.4 to -0.08, p = 0.045; i.e., reduction in net glucose uptake) and the oxidative glucose index (ratio of oxygen to glucose uptake) was reduced by 5.6% (95% CI: -11.2 to 0.06, p = 0.049) with a + 9 mmHg increase in PaCO2. Collectively, the CMRO2 is altered by approximately 1% per mmHg change in PaCO2. Further, glucose is incompletely oxidized during hypercapnia, indicating reductions in CMRO2 are either met by compensatory increases in nonoxidative glucose metabolism or explained by a reduction in total energy production.

End-tidal-to-arterial PCO2 ratio as a prognostic value in mechanically ventilated patients at respiratory intensive care unit

Background Dead space refers to the part of each tidal volume that does not contribute to gas exchange. It serves as an indicator of lung function efficiency. Aim To evaluate the end-tidal-to-arterial PCO2 ratio and Acute Physiological and Chronic Health Assessment (APACHE IV) scoring system as prognostic values in mechanically ventilated patients at the respiratory intensive care unit (ICU). Patients and methods This prospective cohort research was done on 40 mechanically ventilated patients due to different respiratory causes who were admitted at the respiratory ICU at Ain Shams University hospitals. Results This study found that decreasing end tidal PCO2 (PETCO2)/arterial carbon dioxide (PaCO2) is associated with higher mortality amongst mechanically ventilated cases in respiratory ICU. A significant negative association between APACHE IV score and end-tidal to arterial PCO2 ratio following 1 h and after 24 h of mechanical ventilation. APACHE IV score showed a significant relation with mortality, being higher in survivors than nonsurvivors. Conclusion PETCO2/PaCO2 is a relevant prognostic value that reflects dead space ventilation among mechanically ventilated patients in respiratory ICU. APACHE IV score is a good mortality predictor in respiratory ICU.

The Ventilatory Ratio as a Predictor of Successful Weaning from a Veno-Venous Extracorporeal Membrane Oxygenator.

Background: Veno-venous extracorporeal membrane oxygenation (VV-ECMO) is a critical intervention for patients with severe lung failure, especially acute respiratory distress syndrome (ARDS). The weaning process from ECMO relies largely on expert opinion due to a lack of evidence-based guidelines. The ventilatory ratio (VR), which correlates with dead space and mortality in ARDS, is calculated as [minute ventilation (mL/min) x arterial pCO2 (mmHg)]/[predicted body weight × 100 × 37.5]. Objectives: The aim of this study was to determine whether the VR alone can serve as a reliable predictor of safe or unsafe liberation from VV-ECMO in critically ill patients. Methods: A multicenter retrospective analysis was conducted, involving ARDS patients undergoing VV-ECMO weaning at Massachusetts General Hospital (January 2016 - December 2020) and at the University Hospital Aachen (January 2012-December 2021). Safe liberation was defined as no need for ECMO recannulation within 48 h after decannulation. Clinical parameters were obtained for both centers at the same time point: 30 min after the start of the SGOT (sweep gas off trial). Results: Of the patients studied, 83.3% (70/84) were successfully weaned from VV-ECMO. The VR emerged as a significant predictor of unsafe liberation (OR per unit increase: 0.38; CI: 0.17-0.81; p = 0.01). Patients who could not be safely liberated had longer ICU and hospital stays, with a trend towards higher mortality (38% vs. 13%; p = 0.05). Conclusions: The VR may be a valuable predictor for safe liberation from VV-ECMO in ARDS patients, with higher VR values associated with an elevated risk of unsuccessful weaning and adverse clinical outcomes.

Genetic identification of medullary neurons underlying congenital hypoventilation.

Mutations in the transcription factors encoded by PHOX2B or LBX1 correlate with congenital central hypoventilation disorders. These conditions are typically characterized by pronounced hypoventilation, central apnea, and diminished chemoreflexes, particularly to abnormally high levels of arterial PCO2. The dysfunctional neurons causing these respiratory disorders are largely unknown. Here, we show that distinct, and previously undescribed, sets of medullary neurons coexpressing both transcription factors (dB2 neurons) account for specific respiratory functions and phenotypes seen in congenital hypoventilation. By combining intersectional chemogenetics, intersectional labeling, lineage tracing, and conditional mutagenesis, we uncovered subgroups of dB2 neurons with key functions in (i) respiratory tidal volumes, (ii) the hypercarbic reflex, (iii) neonatal respiratory stability, and (iv) neonatal survival. These data provide functional evidence for the critical role of distinct medullary dB2 neurons in neonatal respiratory physiology. In summary, our work identifies distinct subgroups of dB2 neurons regulating breathing homeostasis, dysfunction of which causes respiratory phenotypes associated with congenital hypoventilation.

Selected and shared hematological responses to apnea in elite human free divers and northern elephant seals (Mirounga angustirostris).

Despite elite human free divers achieving incredible feats in competitive free diving, there has yet to be a study that compares consummate divers, (i.e. northern elephant seals) to highly conditioned free divers (i.e., elite competitive free-diving humans). Herein, we compare these two diving models and suggest that hematological traits detected in seals reflect species-specific specializations, while hematological traits shared between the two species are fundamental mammalian characteristics. Arterial blood samples were analyzed in elite human free divers (n = 14) during a single, maximal volitional apnea and in juvenile northern elephant seals (n = 3) during rest-associated apnea. Humans and elephant seals had comparable apnea durations (∼6.5 min) and end-apneic arterial Po2 [humans: 40.4 ± 3.0 mmHg (means ± SE); seals: 27.1 ± 5.9 mmHg; P = 0.2]. Despite similar increases in arterial Pco2 (humans: 33 ± 5%; seals: 16.3 ± 5%; P = 0.2), only humans experienced reductions in pH from baseline (humans: 7.45 ± 0.01; seals: 7.39 ± 0.02) to end apnea (humans: 7.37 ± 0.01; seals: 7.38 ± 0.02; P < 0.0001). Hemoglobin P50 was greater in humans compared to elephant seals (29.9 ± 1.5 and 28.7 ± 0.6 mmHg, respectively; P = 0.046). Elephant seals overall had higher carboxyhemoglobin (COHb) levels (5.9 ± 2.6%) compared to humans (0.8 ± 1.2%; P < 0.0001); however, following apnea, COHb was reduced in seals (baseline: 6.1 ± 0.3%; end apnea: 5.6 ± 0.3%) and was slightly elevated in humans (baseline: 0.7 ± 0.1%; end apnea: 0.9 ± 0.1%; P < 0.0002, both comparisons). Our data indicate that during static apnea, seals have reduced hemoglobin P50, greater pH buffering, and increased COHb levels. The differences in hemoglobin P50 are likely due to the differences in the physiological environment between the two species during apnea, whereas enhanced pH buffering and higher COHb may represent traits selected for in elephant seals.NEW & NOTEWORTHY This study uses similar methods and protocols in elite human free divers and northern elephant seals. Using highly conditioned divers (elite free-diving humans) and highly adapted divers (northern elephant seals), we explored which hematological traits are fundamentally mammalian and which may have been selected for. We found differences in P50, which may be due to different physiological environments between species, while elevated pH buffering and carbon monoxide levels might have been selected for in seals.

Acute Intermittent Hypoxia with Hypercapnia has Complex effects on Phrenic Long-Term Facilitation that Depend on Delivery in the Rest versus Active Phase in Rats

Exploration of mechanisms giving rise to respiratory motor plasticity, such as phrenic long-term facilitation (pLTF) following acute intermittent hypoxia (AIH), has inspired new therapeutic approaches to treat individuals affected by conditions such as spinal cord injury or other clinical disorders. One key step in the translation between rodent models and humans is the apparent need for hypercapnia (either baseline or within hypoxic episodes) during AIH. Whereas AIH consisting of 15, 1-minute hypoxic episodes (1-minute intervals) elicits robust pLTF in rats, similar protocols have minimal impact in humans—unless PaCO2 levels are increased. Although prior studies report that elevated baseline CO2 actually impairs AIH-induced pLTF in rats, the impact of hypercapnia within hypoxic episodes is not known. Thus, we compared AIH with and without concurrent hypercapnia (AIH versus AIHH) on pLTF in anesthetized rats. Since our laboratory recently reported profound time-of-day effects on pLTF magnitude and/or mechanisms, we also compared AIH versus AIHH-induced pLTF during the daily rest and active phase. We hypothesized that AIHH would enhance pLTF versus AIH in both phases, suggesting it may be a more effective intervention to elicit respiratory motor plasticity and respiratory rehabilitation. pLTF was assessed in anesthetized, paralyzed, vagotomized and ventilated male Sprague-Dawley rats ( n=6 per group) exposed to moderate AIH (arterial PO2 = 40-55mmHg) consisting of: 1) 15, 1-minute hypoxic episodes with concurrent hypercapnia (arterial PCO2 ~50mmHg) or 15, 1-minute episodes of isocapnic hypoxia (baseline arterial PCO2 ~2 mmHg above the recruitment threshold; ~40-42 mmHg). We also compared AIHH versus AIH during the active phase using prior published data (AIHH, n = 4; AIH, n = 7; data from Nair et al., Function, 2023 and Marciante et al., Function, 2023, respectively). Contrary to our hypothesis, pLTF was attenuated 90 minutes post-AIHH (37±8%) versus AIH (83±4%; p&lt;0.001) in the rest phase. In striking contrast, during the active phase, pLTF was greater with AIHH (60±11%) versus AIH (30±4%; P=0.012). These unexpected outcomes demonstrate that time of day (or the rest/active phase) must be considered before adding hypercapnia to an AIH protocol. Although the mechanisms of this difference remain unclear, our results make clear that there is still a great deal to learn about mechanisms of AIH-induced respiratory motor plasticity, including the complex interplay between hypoxia, hypercapnia and their impact on pLTF. Supported by: NIH R01 HL147554 &amp; R01 HL148030 (PI: G. Mitchell). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Comparison of BAP65, DECAF, PEARL, and MEWS Scores in Predicting Respiratory Support Need in Hospitalized Exacerbation of Chronic Obstructive Lung Disease Patients

Objective: Prognostic models aid clinical practice with decision-making on treatment and hospitalization in exacerbation of chronic obstructive lung disease (ECOPD). Although there are many studies with prognostic models, diagnostic accuracy is variable within and between models. Subjects and Methods: We compared the prognostic performance of the BAP65 score, DECAF score, PEARL score, and modified early warning score (MEWS) in hospitalized patients with ECOPD, to estimate ventilatory support need. Results: This cross-sectional study consisted of 139 patients. Patients in need of noninvasive or invasive mechanical ventilation support are grouped as ventilatory support groups (n = 54). Comparison between receiver operating characteristic curves revealed that the DECAF score is significantly superior to the PEARL score (p = 0.04) in discriminating patients in need of ventilatory support. DECAF score with a cutoff value of 1 presented the highest sensitivity and BAP65 score with a cutoff value of 2 presented the highest specificity in predicting ventilatory support need. Multivariable analysis revealed that gender played a significant role in COPD exacerbation outcome, and arterial pCO2 and RDW measurements were also predictors of ventilatory support need. Within severity indexes, only the DECAF score was independently associated with the outcome. One-point increase in DECAF score created a 1.43 times higher risk of ventilatory support need. All severity indexes showed a correlation with age, comorbidity index, and dyspnea. BAP65 and DECAF scores also showed a correlation with length of stay. Conclusion: Objective and practical classifications are needed by clinicians to assess prognosis and initiate treatment accordingly. DECAF score is a strong candidate among severity indexes.

Effects of low protein diets on acid-base balance, electrolyte balance, intestinal structure, and amino acid transport in piglets.

Reducing the dietary crude protein (CP) could effectively reduce pressure on protein ingredient supplies. However, few data have been reported about the extent to which CP can be reduced and whether limiting the use of soybean meal leads to electrolyte imbalance. In this experiment, using the low protein (LP) diet [2% lower than NRC (2012)], seventy-two piglets (35 days old) were randomly divided into 2 groups with 6 replicates of 6 piglets each: CON group (CP = 18.5%) and LP group (CP = 16.5%), to investigate the effect of the LP diet on electrolyte balance, acid-base balance, intestinal structure and amino acid transport in piglets. The results revealed that the LP diet decreased the average daily gain and dietary CP digestibility, and damaged the villi structure of the small intestine. Compared with the CON diet, the potassium content decreased and the chlorine content increased in the LP diet, and similar trends were shown in piglet serum. The arterial pH, pCO2, HCO3 -, and base excess of piglets in the LP group were lower than those in the CON group, while pO2 was higher than those in the CON group. Interestingly, the LP diet significantly increased the lysine content in piglet serum and significantly decreased the levels of arginine, leucine, and glutamic acid. Furthermore, the LP diet significantly affected the expression of some amino acid transport vectors (B0AT1, EAAC1, and y+LAT1). In summary, these findings suggested that the LP diet leads to acid-base imbalance, amino acid transport disorder and amino acids imbalance in piglets, and the dietary electrolyte may be a key factor in the impact of the LP diet on piglet growth performance and intestinal health.

Relationship between maternal arterial and foetal cord carbon dioxide tension and neonatal outcome in critically ill pregnant women at delivery.

No studies have evaluated the relationship between maternal arterial partial pressure of carbon dioxide (mPaCO2) and umbilical cord venous partial pressure of carbon dioxide (PCO2) in critically ill pregnant women at delivery. Based on the studies in healthy pregnant women, an mPaCO2 target of ≤50 mmHg is a suggested threshold during mechanical ventilation in critically ill parturients. We evaluated the relationship between mPaCO2 and neonatal cord gases in critically ill parturients at delivery as the primary objective. The relationship between mPaCO2 and APGAR scores at delivery was also analysed as a secondary objective. Maternal and neonatal cord gas data at delivery and APGAR scores were obtained by a retrospective chart review of 25 consecutive parturients with severe respiratory compromise who were delivered during mechanical ventilation. Linear regression was used to assess the relationship between mPaCO2 and umbilical artery and vein PCO2 and between mPaCO2 and APGAR scores at 1 and 5 min. There was a positive correlation between mPaCO2 and neonatal cord venous PCO2 (P = 0.013). Foetal venous PCO2 exceeded predelivery mPaCO2 by 17.5 (7.5) mmHg. There was an inverse relationship between mPaCO2 and neonatal APGAR scores at 1 and 5 min (P = 0.006 and P = 0.007, respectively). Foetal cord venous PCO2 can be predicted if mPaCO2 values are known. Unlike in healthy pregnant women, there was an inverse relationship between rising mPaCO2 levels and neonatal APGAR scores in critically ill pregnant women who had several associated compounding factors.

Multiple blood gas variables predict AKI survival in an independent manner

Background and aimAcute kidney injury (AKI) is becoming increasingly prevalent among hospitalized patients and carries a poor prognosis. While new biomarkers show promise in identifying early stages of AKI, accurately predicting severe outcomes such as the need for kidney replacement therapy (KRT) or death remains a challenge. However, blood gas analyses (BGA) can be used to diagnose life-threatening complications associated with AKI. The objective of this study was to assess the role of BGA as a biomarker panel in both emerging and established cases of AKI.MethodsRetrospective observational study examining subjects with newly developed acute kidney injury (AKI). The study will document venous and arterial pH, pCO2, and actual bicarbonate levels upon hospital admission and at the onset of AKI. The primary endpoints include in-hospital mortality, the need for kidney replacement therapy (KRT), and the recovery of kidney function (ROKF).ResultsA total of 202 individuals were included in the study. Three variables were found to be independent predictors of in-hospital survival: admission arterial pH, arterial pH at acute kidney injury (AKI) onset, and arterial pCO2 at AKI onset. Additionally, venous pCO2 at AKI onset was identified as an independent predictor for the need of kidney replacement therapy (KRT).ConclusionsOur study suggests that blood gas analysis may have a potential role in predicting severe outcome variables in acute kidney injury (AKI). The associated costs are minimal.