Comparison of volume-controlled, pressure-controlled, and pressure-controlled volume-guaranteed ventilation during robot-assisted laparoscopic gynecologic surgery in the Trendelenburg position.

Background: Pressure-controlled ventilation volume-guaranteed (PCV-VG) is being increasingly used for ventilation during general anesthesia. Carbon dioxide (CO2) pneumoperitoneum in the Trendelenburg position is routinely used during robot-assisted laparoscopic gynecologic surgery. Here, we hypothesized that PCV-VG would reduce peak inspiratory pressure (Ppeak), compared to volume-controlled ventilation (VCV) and pressure-controlled ventilation (PCV). Methods: In total, 60 patients were enrolled in this study and randomly assigned to receive VCV, PCV, or PCV-VG. Hemodynamic variables, respiratory variables, and arterial blood gases were measured in the supine position 15 minutes after the induction of anesthesia (T0), 30 and 60 minutes after CO2 pneumoperitoneum and Trendelenburg positioning (T1 and T2, respectively), and 15 minutes after placement in the supine position at the end of anesthesia (T3). Results: The Ppeak was higher in the VCV group than in the PCV and PCV-VG groups (p=0.011). Mean inspiratory pressure (Pmean) was higher in the PCV and PCV-VG groups than in the VCV group (p<0.001). Dynamic lung compliance (Cdyn) was lower in the VCV group than in the PCV and PCV-VG groups (p=0.001). Conclusion: Compared to VCV, PCV and PCV-VG provided lower Ppeak, higher Pmean, and improved Cdyn, without significant differences in hemodynamic variables or arterial blood gas results during robot-assisted laparoscopic gynecologic surgery with Trendelenburg position.

Cardiovascular effects of intravenous colforsin in normal and acute respiratory acidosis canine models: A dose-response study.

In acidosis, catecholamines are attenuated, and higher doses are often required to improve cardiovascular function. Colforsin activates adenylate cyclase in cardiomyocytes without beta-adrenoceptor. Here, six beagles were administered colforsin or dobutamine four times during eucapnia (partial pressure of arterial carbon dioxide 35-40 mm Hg; normal) and hypercapnia (ibid 90-110 mm Hg; acidosis) conditions. The latter was induced by CO2 inhalation. Anesthesia was induced with propofol and maintained with isoflurane. Cardiovascular function was measured by thermodilution and a Swan-Ganz catheter at baseline and 60 min after 0.3 µg/kg/min (low), 0.6 µg/kg/min (middle), and 1.2 µg/kg/min (high) colforsin administration. The median pH was 7.38 [range 7.33-7.42] and 7.01 [range 6.96-7.08] at baseline in the Normal and Acidosis conditions, respectively. Endogenous adrenaline and noradrenaline levels at baseline were significantly (P < 0.05) higher in the Acidosis than in the Normal condition. Colforsin induced cardiovascular effects similar to those caused by dobutamine. Colforsin increased cardiac output in the Normal condition (baseline: 3.9 ± 0.2 L/kg/m2 [mean ± standard error], low: 5.2 ± 0.4 L/kg/min2, middle: 7.0 ± 0.4 L/kg/m2, high: 9.4 ± 0.2 L/kg/m2; P < 0.001) and Acidosis condition (baseline: 6.1 ± 0.3 L/kg/m2, low: 6.2 ± 0.2 L/kg/m2, middle: 7.2 ± 0.2 L/kg/m2, high: 8.3 ± 0.2 L/kg/m2; P < 0.001). Colforsin significantly increased heart rate and decreased systemic vascular resistance compared to values at baseline. Both drugs increased pulmonary artery pressure, but colforsin (high: 13.3 ± 0.6 mmHg in Normal and 20.1 ± 0.2 mmHg in Acidosis) may have lower clinical impact on the pulmonary artery than dobutamine (high: 19.7 ± 0.6 in Normal and 26.7 ± 0.5 in Acidosis). Interaction between both drugs and experimental conditions was observed in terms of cardiovascular function, which were similarly attenuated with colforsin and dobutamine under acute respiratory acidosis.

Ischemic priapism as a model of exhausted metabolism.

In vivo metabolic studies typically concern complex open systems. However, a closed system allows better assessment of the metabolic limits. Ischemic priapism (IP) constitutes a special model of the compartment syndrome that allows direct sampling from a relatively large blood compartment formed by the corpora cavernosa (CC). The purpose of our study was to measure metabolic changes and the accumulation of end products within the CC during IP. Blood gas and biochemical analyses of aspirates of the CC were analyzed over an 8-year period. Mean ± SD pH, pCO2 , pO2 , O2 -saturation, lactate, and glucose of the aspirated blood were determined with a point-of-care analyzer. Forty-seven initial samples from 21 patients had a pH of 6.91 ± 0.16, pCO2 of 15.3 ± 4.4 kPa, pO2 of 2.4 ± 2.0 kPa, and an O2 -saturation of 19 ± 24% indicating severe hypoxia with severe combined respiratory and metabolic acidosis. Glucose and lactate levels were 1.1 ± 1.5 and 14.6 ± 4.8 mmol/L, respectively. pH and pCO2 were inversely correlated (R2  = 0.86; P < 0.001), glucose and O2 -saturation were positively correlated (R2  = 0.83; P < 0.001), and glucose and lactate were inversely correlated (R2  = 0.72; P < 0.001). The positive correlation of CO2 and lactate (R2  = 0.69; P < 0.001) was similar to that observed in vitro, when blood was titrated with lactic acid. The observed combined acidosis underscores that IP behaves as a closed system where severe hypoxia and glycopenia coexist, indicating that virtually all energy reserves have been consumed.

Neonatal cardiopulmonary transition in an ovine model of congenital diaphragmatic hernia.

OBJECTIVE: Infants with a congenital diaphragmatic hernia (CDH) are at high risk of developing pulmonary hypertension after birth, but little is known of their physiological transition at birth. We aimed to characterise the changes in cardiopulmonary physiology during the neonatal transition in an ovine model of CDH. METHODS: A diaphragmatic hernia (DH) was surgically created at 80 days of gestational age (dGA) in 10 fetuses, whereas controls underwent sham surgery (n=6). At 138 dGA, lambs were delivered via caesarean section and ventilated for 2 hours. Physiological and ventilation parameters were continuously recorded, and arterial blood gas values were measured. RESULTS: DH lambs had lower wet lung-to-body-weight ratio (0.016±0.002vs0.033±0.004), reduced dynamic lung compliance (0.4±0.1mL/cmH2O vs1.2±0.1 mL/cmH2O) and reduced arterial pH (7.11±0.05vs7.26±0.05), compared with controls. While measured pulmonary blood flow (PBF) was lower in DH lambs, after correction for lung weight, PBF was not different between groups (4.05±0.60mL/min/gvs4.29±0.57 mL/min/g). Cerebral tissue oxygen saturation was lower in DH compared with control lambs (55.7±3.5vs67.7%±3.9%). CONCLUSIONS: Immediately after birth, DH lambs have small, non-compliant lungs, respiratory acidosis and poor cerebral oxygenation that reflects the clinical phenotype of human CDH. PBF (indexed to lung weight) was similar in DH and control lambs, suggesting that the reduction in PBF associated with CDH is proportional to the degree of lung hypoplasia during the neonatal cardiopulmonary transition.

Feasibility and safety of extracorporeal CO2 removal to enhance protective ventilation in acute respiratory distress syndrome: the SUPERNOVA study.

PURPOSE: We assessed feasibility and safety of extracorporeal carbon dioxide removal (ECCO2R) to facilitate ultra-protective ventilation (VT 4 mL/kg and PPLAT ≤ 25 cmH2O) in patients with moderate acute respiratory distress syndrome (ARDS). METHODS: Prospective multicenter international phase 2 study. Primary endpoint was the proportion of patients achieving ultra-protective ventilation with PaCO2 not increasing more than 20% from baseline, and arterial pH > 7.30. Severe adverse events (SAE) and ECCO2R-related adverse events (ECCO2R-AE) were reported to an independent data and safety monitoring board. We used lower CO2 extraction and higher CO2 extraction devices (membrane lung cross-sectional area 0.59 vs. 1.30 m2; flow 300-500 mL/min vs. 800-1000 mL/min, respectively). RESULTS: Ninety-five patients were enrolled. The proportion of patients who achieved ultra-protective settings by 8 h and 24 h was 78% (74 out of 95 patients; 95% confidence interval 68-89%) and 82% (78 out of 95 patients; 95% confidence interval 76-88%), respectively. ECCO2R was maintained for 5 [3-8] days. Six SAEs were reported; two of them were attributed to ECCO2R (brain hemorrhage and pneumothorax). ECCO2R-AEs were reported in 39% of the patients. A total of 69 patients (73%) were alive at day 28. Fifty-nine patients (62%) were alive at hospital discharge. CONCLUSIONS: Use of ECCO2R to facilitate ultra-protective ventilation was feasible. A randomized clinical trial is required to assess the overall benefits and harms. CLINICALTRIALS.GOV: NCT02282657.

Inadequacy of Pulse Oximetry in the Catheterization Laboratory. An Exploratory Study Monitoring Respiratory Status Using Arterial Blood Gases during Cardiac Catheterization with Conscious Sedation.

BACKGROUND: Benzodiazepines and opioids are commonly used for conscious sedation (CS) in cardiac catheterization laboratory (CCL) patients. Both drugs are known to predispose to hypoxemia, apnea and decreased responsiveness to PCO2, resulting in decreased arterial pH and PO2, as well as increased PCO2. We want to determine the effects of CS on arterial blood gas (ABG) in CCL patient, and identify if pulse oximetry monitoring is adequate. METHODS: We enrolled 18 subjects undergoing elective catheterization. Measurement of ABGs at one-minute intervals was done from the moment of arterial access until case end. The results of ABGs were not available to the clinician who administered sedation. Relationships of pH, PCO2, PaO2 and SaO2 were studied by plotting time series graphs. Significant changes were defined as pH <7.30, SaO2 < 90, and PCO2 > 50 mmHg. RESULTS: No significant change in pH, PCO2, PaO2 and SaO2 was noted in 4/18 (22%) subjects. A significant drop in SaO2 was noted in 4/18 (22%). A significant change in PCO2 and/or pH was noted in 10/18 (55%) cases. Among the 16 (16/18) subjects receiving supplemental oxygen, 7 (7/18, 39%) had no drop in SaO2, but developed respiratory acidosis. At the end of the case, 5/18 (28%) subjects had respiratory acidosis with normal PaO2. CONCLUSION: Significant hypercarbia and acidosis occurred frequently in this small study during CS in patients undergoing cardiac catheterization. Relying on pulse oximetry alone especially with patients on supplemental oxygen may lead to failure in detecting respiratory acidosis in a significant number of patients.

Effects of lung protective mechanical ventilation associated with permissive respiratory acidosis on regional extra-pulmonary blood flow in experimental ARDS.

BACKGROUND: Lung protective mechanical ventilation with limited peak inspiratory pressure has been shown to affect cardiac output in patients with ARDS. However, little is known about the impact of lung protective mechanical ventilation on regional perfusion, especially when associated with moderate permissive respiratory acidosis. We hypothesized that lung protective mechanical ventilation with limited peak inspiratory pressure and moderate respiratory acidosis results in an increased cardiac output but unequal distribution of blood flow to the different organs of pigs with oleic-acid induced ARDS. METHODS: Twelve pigs were enrolled, 3 died during instrumentation and induction of lung injury. Thus, 9 animals received pressure controlled mechanical ventilation with a PEEP of 5 cmH2O and limited peak inspiratory pressure (17 ± 4 cmH2O) versus increased peak inspiratory pressure (23 ± 6 cmH2O) in a crossover-randomized design and were analyzed. The sequence of limited versus increased peak inspiratory pressure was randomized using sealed envelopes. Systemic and regional hemodynamics were determined by double indicator dilution technique and colored microspheres, respectively. The paired student t-test and the Wilcoxon test were used to compare normally and not normally distributed data, respectively. RESULTS: Mechanical ventilation with limited inspiratory pressure resulted in moderate hypercapnia and respiratory acidosis (PaCO2 71 ± 12 vs. 46 ± 9 mmHg, and pH 7.27 ± 0.05 vs. 7.38 ± 0.04, p < 0.001, respectively), increased cardiac output (140 ± 32 vs. 110 ± 22 ml/min/kg, p<0.05) and regional blood flow in the myocardium, brain and spinal cord, adrenal and thyroid glands, the mucosal layers of the esophagus and jejunum, the muscularis layers of the esophagus and duodenum, and the gall and urinary bladders. Perfusion of kidneys, pancreas, spleen, hepatic arterial bed, and the mucosal and muscularis blood flow to the other evaluated intestinal regions remained unchanged. CONCLUSIONS: In this porcine model of ARDS mechanical ventilation with limited peak inspiratory pressure resulting in moderate respiratory acidosis was associated with an increase in cardiac output. However, the better systemic blood flow was not uniformly directed to the different organs. This observation may be of clinical interest in patients, e.g. with cardiac, renal and cerebral pathologies.

Delayed but successful response to noninvasive ventilation in COPD patients with acute hypercapnic respiratory failure.

BACKGROUND: We evaluated a new noninvasive ventilation (NIV) protocol that allows the pursuit of NIV in the case of persistent severe respiratory acidosis despite a first NIV challenge in COPD patients with acute hypercapnic respiratory failure (AHRF). PATIENTS AND METHODS: A prospective observational multicentric pilot study was conducted in three tertiary hospitals over a 12-month study period. A total of 155 consecutive COPD patients who were admitted for AHRF and treated by NIV were enrolled. Delayed response to NIV was defined as a significant clinical improvement in the first 48 h following NIV initiation despite a persistent severe respiratory acidosis (pH <7.30) after the first 2 h of NIV trial. RESULTS: NIV failed in only 10 patients (6.5%). Delayed responders to NIV (n=83, 53%) exhibited similar nutritional status, comorbidities, functional status, frailty score, dyspnea score, and severity score at admission, compared with early responders (n=62, 40%). Only age (66 vs 70 years in early responders; P=0.03) and encephalopathy score (3 [2-4] vs 3 [2-4] in early responders; P=0.015) were different among the responders. Inhospital mortality did not differ between responders to NIV (n=10, 12% for delayed responders vs n=10, 16% for early responders, P=0.49). A second episode of AHRF occurred in 20 responders (14%), equally distributed among early and delayed responders to NIV (n=9, 14.5% in early responders vs n=11, 13% in delayed responders; P=0.83), with a poor survival rate (n=1, 5%). CONCLUSION: Most of the COPD patients with AHRF have a successful outcome when NIV is pursued despite a persistent severe respiratory acidosis after the first NIV trial. The outcome of delayed responders is similar to the one of the early responders. On the contrary, the second episode of AHRF during the hospital stay carries a poor prognosis.

Effect of arterial puncture on ventilation.

BACKGROUND: Clinicians frequently assume that during arterial puncture for measuring arterial blood gases patients hyperventilate from pain and anxiety. This assumption leads clinicians to falsely interpret a PaCO2 and pH near the upper limit of normal as a chronic respiratory acidosis corrected by an acute respiratory alkalosis. OBJECTIVE: Determine if participants hyperventilate during arterial puncture from pain and anxiety. METHODS: We recruited participants from a pulmonary function laboratory referred for arterial blood gas measurement. We excluded those with heart failure and included those with any respiratory condition (COPD, asthma, sleep apnea). We measured end tidal PCO2 (PETCO2), respiratory rate, and heart rate 15 min before topical anesthesia, during anesthesia, during arterial puncture, and 15 min later. We assessed generalized anxiety before and measured pain during and after arterial puncture. RESULTS: 24 participants were recruited (age: 54 ± 12 years; men: 54%). PaCO2 was 41 ± 5 mmHg. One had acute respiratory alkalosis. Respiratory rate increased from (19 ± 6 breaths per minute (bpm)) before to a maximum (21 ± 6 bpm) during arterial puncture (p = 0.001). Heart rate was stable throughout. The lowest PETCO2 during the procedure (35 ± 5) was similar to PETCO2 before the procedure (p = 0.1). The change in PETCO2 and respiratory rate did not correlate with pain, anxiety, or lung function. CONCLUSION: Respiratory rate increased slightly during arterial puncture without any change in PETCO2. Hence, acid-base status must be interpreted without the assumption of procedure induced hyperventilation.

Nasal flaring as a clinical sign of respiratory acidosis in patients with dyspnea.

OBJECTIVE: To determine whether the presence of nasal flaring is a clinical sign of respiratory acidosis in patients attending emergency departments for acute dyspnea. METHODS: Single-center, prospective, observational study of patients aged over 15 requiring urgent attention for dyspnea, classified as level II or III according to the Andorran Triage Program and who underwent arterial blood gas test on arrival at the emergency department. The presence of nasal flaring was evaluated by two observers. Demographic and clinical variables, signs of respiratory difficulty, vital signs, arterial blood gases and clinical outcome (hospitalization and mortality) were recorded. Bivariate and multivariate analyses were performed using logistic regression models. RESULTS: The sample comprised 212 patients, mean age 78years (SD=12.8), of whom 49.5% were women. Acidosis was recorded in 21.2%. Factors significantly associated with the presence of acidosis in the bivariate analysis were the need for pre-hospital medical care, triage level II, signs of respiratory distress, presence of nasal flaring, poor oxygenation, hypercapnia, low bicarbonates and greater need for noninvasive ventilation. Nasal flaring had a positive likelihood ratio for acidosis of 4.6 (95% CI 2.9-7.4). In the multivariate analysis, triage level II (aOR 5.16; 95% CI: 1.91 to 13.98), the need for oxygen therapy (aOR 2.60; 95% CI: 1.13-5.96) and presence of nasal flaring (aOR 6.32; 95% CI: 2.78-14.41) were maintained as factors independently associated with acidosis. CONCLUSIONS: Nasal flaring is a clinical sign of severity in patients requiring urgent care for acute dyspnea, which has a strong association with acidosis and hypercapnia.

[Hypercapnic respiratory failure. Pathophysiology, indications for mechanical ventilation and management]. / Hyperkapnisches Atemversagen. Pathophysiologie, Beatmungsindikationen und -durchführung.

BACKGROUND: Acute hypercapnic respiratory failure is mostly seen in patients with chronic obstructive pulmonary disease (COPD) and obesity hypoventilation syndrome (OHS). Depending on the underlying cause it may be associated with hypoxemic respiratory failure and places high demands on mechanical ventilation. OBJECTIVE: Presentation of the current knowledge on indications and management of mechanical ventilation in patients with hypercapnic respiratory failure. MATERIAL AND METHODS: Review of the literature. RESULTS: Important by the selection of mechanical ventilation procedures is recognition of the predominant pathophysiological component. In hypercapnic respiratory failure with a pH < 7.35 non-invasive ventilation (NIV) is primarily indicated unless there are contraindications. In patients with severe respiratory acidosis NIV requires a skilled and experienced team and close monitoring in order to perceive a failure of NIV. In acute exacerbation of COPD ventilator settings need a long expiration and short inspiration time to avoid further hyperinflation and an increase in intrinsic positive end-expiratory pressure (PEEP). Ventilation must be adapted to the pathophysiological situation in patients with OHS or overlap syndrome. If severe respiratory acidosis and hypercapnia cannot be managed by mechanical ventilation therapy alone extracorporeal venous CO2 removal may be necessary. Reports on this approach in awake patients are available. CONCLUSION: The use of NIV is the predominant treatment in patients with hypercapnic respiratory failure but close monitoring is necessary in order not to miss the indications for intubation and invasive ventilation. Methods of extracorporeal CO2 removal especially in awake patients need further evaluation.

The Effects of Lung Protective Ventilation or Hypercapnic Acidosis on Gas Exchange and Lung Injury in Surfactant Deficient Rabbits.

BACKGROUND: Permissive hypercapnia has been shown to reduce lung injury in subjects with surfactant deficiency. Experimental studies suggest that hypercapnic acidosis by itself rather than decreased tidal volume may be a key protective factor. OBJECTIVES: To study the differential effects of a lung protective ventilatory strategy or hypercapnic acidosis on gas exchange, hemodynamics and lung injury in an animal model of surfactant deficiency. METHODS: 30 anesthetized, surfactant-depleted rabbits were mechanically ventilated (FiO2 = 0.8, PEEP = 7cmH2O) and randomized into three groups: Normoventilation-Normocapnia (NN)-group: tidal volume (Vt) = 7.5 ml/kg, target PaCO2 = 40 mmHg; Normoventilation-Hypercapnia (NH)-group: Vt = 7.5 ml/kg, target PaCO2 = 80 mmHg by increasing FiCO2; and a Hypoventilation-Hypercapnia (HH)-group: Vt = 4.5 ml/kg, target PaCO2 = 80 mmHg. Plasma lactate and interleukin (IL)-8 were measured every 2 h. Animals were sacrificed after 6 h to perform bronchoalveolar lavage (BAL), to measure lung wet-to-dry weight, lung tissue IL-8, and to obtain lung histology. RESULTS: PaO2 was significantly higher in the HH-group compared to the NN-group (p<0.05), with values of the NH-group between the HH- and NN-groups. Other markers of lung injury (wet-dry-weight, BAL-Protein, histology-score, plasma-IL-8 and lung tissue IL-8) resulted in significantly lower values for the HH-group compared to the NN-group and trends for the NH-group towards lower values compared to the NN-group. Lactate was significantly lower in both hypercapnia groups compared to the NN-group. CONCLUSION: Whereas hypercapnic acidosis may have some beneficial effects, a significant effect on lung injury and systemic inflammatory response is dependent upon a lower tidal volume rather than resultant arterial CO2 tensions and pH alone.

Differences in baseline factors and survival between normocapnia, compensated respiratory acidosis and decompensated respiratory acidosis in COPD exacerbation: A pilot study.

BACKGROUND AND OBJECTIVE: Patients with chronic obstructive pulmonary disease (COPD) experiencing acute exacerbation (AE-COPD) with decompensated respiratory acidosis are known to have poor outcomes in terms of recurrent respiratory failure and death. However, the outcomes of AE-COPD patients with compensated respiratory acidosis are not known. METHODS: We performed a 1-year prospective, single-centre, cohort study in patients surviving the index admission for AE-COPD to compare baseline factors between groups with normocapnia, compensated respiratory acidosis and decompensated respiratory acidosis. Survival analysis was done to examine time to readmissions, life-threatening events and death. RESULTS: A total of 250 patients fulfilling the inclusion and exclusion criteria were recruited and 245 patients were analysed. Compared with normocapnia, both compensated and decompensated respiratory acidosis are associated with lower FEV1 % (P < 0.001), higher GOLD stage (P = 0.003, <0.001) and higher BODE index (P = 0.038, 0.001) and a shorter time to life-threatening events (P < 0.001). Comparing compensated and decompensated respiratory acidosis, there was no difference in FEV1 (% predicted) (P = 0.15), GOLD stage (P = 0.091), BODE index (P = 0.158) or time to life-threatening events (P = 0.301). High PaCO2 level (P = 0.002) and previous use of non-invasive ventilation (NIV) in acute setting (P < 0.001) are predictive factors of future life-threatening events by multivariate analysis. CONCLUSIONS: Compared with normocapnia, both compensated and decompensated respiratory acidosis are associated with poorer lung function and higher risk of future life-threatening events. High PaCO2 level and past history of NIV use in acute settings were predictive factors for future life-threatening events. Compensated respiratory acidosis warrants special attention and optimization of medical therapy as it poses risk of life-threatening events.

PHYSIOLOGY. Regulation of breathing by CO2 requires the proton-activated receptor GPR4 in retrotrapezoid nucleus neurons.

Blood gas and tissue pH regulation depend on the ability of the brain to sense CO2 and/or H(+) and alter breathing appropriately, a homeostatic process called central respiratory chemosensitivity. We show that selective expression of the proton-activated receptor GPR4 in chemosensory neurons of the mouse retrotrapezoid nucleus (RTN) is required for CO2-stimulated breathing. Genetic deletion of GPR4 disrupted acidosis-dependent activation of RTN neurons, increased apnea frequency, and blunted ventilatory responses to CO2. Reintroduction of GPR4 into RTN neurons restored CO2-dependent RTN neuronal activation and rescued the ventilatory phenotype. Additional elimination of TASK-2 (K(2P)5), a pH-sensitive K(+) channel expressed in RTN neurons, essentially abolished the ventilatory response to CO2. The data identify GPR4 and TASK-2 as distinct, parallel, and essential central mediators of respiratory chemosensitivity.

Comparison of the effects of moderate and severe hypercapnic acidosis on ventilation-induced lung injury.

BACKGROUND: We have proved that hypercapnic acidosis (a PaCO2 of 80-100 mmHg) protects against ventilator-induced lung injury in rats. However, there remains uncertainty regarding the appropriate target PaCO2 or if greater CO2 "doses" (PaCO2 > 100 mmHg) demonstrate this effect. We wished to determine whether severe acute hypercapnic acidosis can reduce stretch-induced injury, as well as the role of nuclear factor-κB (NF-κB) in the effects of acute hypercapnic acidosis. METHODS: Fifty-four rats were ventilated for 4 hours with a pressure-controlled ventilation mode set at a peak inspiratory pressure (PIP) of 30 cmH2O. A gas mixture of carbon dioxide with oxygen (FiCO2 = 4-5%, FiCO2 = 11-12% or FiCO2 = 16-17%; FiO2 = 0.7; balance N2) was immediately administered to maintain the target PaCO2 in the NC (a PaCO2 of 35-45 mmHg), MHA (a PaCO2 of 80-100 mmHg) and SHA (a PaCO2 of 130-150 mmHg) groups. Nine normal or non-ventilated rats served as controls. The hemodynamics, gas exchange and inflammatory parameters were measured. The role of NF-κB pathway in hypercapnic acidosis-mediated protection from high-pressure stretch injury was then determined. RESULTS: In the NC group, high-pressure ventilation resulted in a decrease in PaO2/FiO2 from 415.6 (37.1) mmHg to 179.1 (23.5) mmHg (p < 0.001), but improved by MHA (379.9 ± 34.5 mmHg) and SHA (298.6 ± 35.3 mmHg). The lung injury score in the SHA group (7.8 ± 1.6) was lower than the NC group (11.8 ± 2.3, P < 0.05) but was higher than the MHA group (4.4 ± 1.3, P < 0.05). Compared with the NC group, after 4 h of high pressure ventilation, the MHA and SHA groups had decreases in MPO activity of 67% and 33%, respectively, and also declined the levels of TNF-α (58% versus 72%) and MIP-2 (76% versus 60%) in the BALF. Additionally, both hypercapnic acidosis groups reduced stretch-induced NF-κB activation (p < 0.05) and significantly decreased lung ICAM-1 expression (p < 0.05). CONCLUSIONS: Moderate hypercapnic acidosis (PaCO2 maintained at 80-100 mmHg) has a greater protective effect on high-pressure ventilation-induced inflammatory injury. The potential mechanisms may involve alterations in NF-κB activity.

Hypercapnic thresholds for embryonic acid-base metabolic compensation and hematological regulation during CO2 challenges in layer and broiler chicken strains.

Time specific acid-base metabolic compensation and responses of hematological respiratory variables were measured in day 15 layer (Hyline) and broiler (Cornish Rock) chicken embryos during acute hypercapnic challenges (3, 6, 10 and 20% CO2). Control acid-base status and hematology differed between two strains. Broiler embryos were relatively respiratory acidotic and had higher hematocrit (Hct) and hemoglobin concentration. The partial metabolic compensation for respiratory acidosis produced by ≤ 10% CO2 exposures occurred in proportion to CO2 concentrations in both strains, but metabolic compensation for 20% CO2 respiratory acidosis was depressed at 2, 6 and 24h, particularly in broiler embryos. Exposure to ≤ 10% CO2 induced the same hematological responses across CO2 concentrations; i.e., Hct and mean corpuscular volume (MCV) increased while RBC concentration remained unchanged. In response to 20% CO2 exposure, Hct and MCV increased dramatically in both stains. Consequently, altered acid-base and hematology responses to 20% CO2 exposure compared to ≤ 10% CO2 suggest that the hypercapnic threshold to compensation for acidosis and regulation of hematology is >10% CO2.