Hypercapnic Group Research Articles

Therapeutic hypercapnia improves functional recovery and attenuates injury via antiapoptotic mechanisms in a rat focal cerebral ischemia/reperfusion model

Recent studies have demonstrated neuroprotective effects of therapeutic hypercapnia for different forms of brain injury. However, few studies have assessed the neuroprotective and neurobehavioral effects of hypercapnia in focal cerebral ischemia, and the underlying mechanisms are still unclear. Here, we investigated the effects of therapeutic hypercapnia in focal cerebral ischemia in the rat middle cerebral artery occlusion/reperfusion (MCAO/R) model. Adult male Sprague Dawley rats were subjected to 90min of MCAO/R and subsequently exposed to increased carbon dioxide (CO2) levels to maintain arterial blood CO2 tension (PaCO2) between 80 and 100mmHg for 2h. Neurological deficits were evaluated with the corner test at days 1, 7, 14, and 28. Infarction volume and apoptotic changes were assessed by 2, 3, 7-triphenyltetrazolium chloride (TTC) staining, and terminal deoxynucleotidyl transferase-mediated 2′-deoxyuridine 5′-triphosphate-biotin nick end labeling (TUNEL) staining at 24h after reperfusion. Apoptosis-related proteins (Bcl-2, Bax, cytochrome c, and caspase-3) were investigated by western blotting. The results of this study showed that therapeutic hypercapnia significantly reduced infarct volume and improved neurological scores after MCAO/R. Moreover, hypercapnia treatment increased the survival rate at 28 days after reperfusion. The TUNEL-positive neurons in the ipsilateral cortex were significantly decreased in the hypercapnia group. Mitochondrial Bcl-2 and Bax cortical expression levels were significantly higher and lower, respectively, in hypercapnia-treated rats. In addition, hypercapnia treatment decreased cytosolic cytochrome c and cleaved caspase-3 expression and increased cytosolic Bax expression. These findings indicate that therapeutic hypercapnia preserves brain tissue and promotes functional neurological recovery through antiapoptotic mechanisms.

Acute, short-term hypercapnia improves microvascular oxygenation of the colon in an animal model of sepsis

IntroductionThe deterioration of microcirculatory oxygenation of the gut plays a vital role in the development of sepsis. Acute hypercapnia enhances the microcirculatory oxygenation of the splanchnic region under physiological conditions, while the effect of hypercapnia under sepsis is unknown. The aim of this study was to investigate the effects of acute hypercapnia and hypercapnic acidosis on the colonic microcirculation and early cytokine response in polymicrobial sepsis. MethodsExperiments were performed on 103 male Wistar rats. Colon ascendens stent peritonitis (CASP) surgery with varying stent diameters was conducted to establish a moderate polymicrobial sepsis model. In a second series, 24h of sepsis development induced by CASP surgery was followed by 120min of volume-controlled and pressure-limited ventilation with either normocapnic (pCO2 45±5mmHg) or moderate hypercapnic ventilation targets (pCO2 75±5mmHg) via exogenous carbon dioxide application. The effect of acidosis was investigated by metabolically buffering the hypercapnic acidosis with tromethamine. Microcirculatory oxygenation of the colon wall (tissue reflectance spectrophotometry) and hemodynamic variables were recorded continuously and arterial blood gas and cytokine (TNF-α, IL-6, IL-10) levels were analyzed intermittently. ResultsIn septic animals the microcirculatory oxygenation of the colon deteriorated under normocapnia (−7.0±7.6% at 90min) but was maintained under hypercapnic acidosis (+3.6±7.6%) and buffered hypercapnia (+1.5±4.4%). Cytokine levels were significantly higher in septic animals as opposed to sham animals but did not differ between normocapnic and hypercapnic groups. ConclusionsAcute hypercapnic acidosis and buffered hypercapnia both improve splanchnic microcirculatory oxygenation in a septic animal model, thereby counteracting the adverse effect induced by sepsis. The circulating pro- and anti-inflammatory cytokine levels are not modulated after 120min of hypercapnia.

Post‐operative hypercapnia‐induced hyperpnoea accelerates recovery from sevoflurane anaesthesia: a prospective randomised controlled trial

The time to recovery from vapour anaesthesia is shortened by an increase in ventilation while maintaining normocapnia. Hypercapnia during emergence from anaesthesia in spontaneously breathing patients also increases anaesthetic clearance from the brain by increasing cerebral blood flow. We hypothesised that hypercapnia-induced hyperpnoea accelerates emergence from sevoflurane anaesthesia compared to the standard anaesthesia protocol. After Ethics Review Board approval, 44 ASA I-III patients undergoing elective gynaecological surgery were randomised after surgery to either hypercapnic hyperpnoea or control groups. In the hypercapnic hyperpnoea group, the end-tidal CO2 was adjusted to a range of 6.0-7.3 kPa to maintain a minute ventilation of 10-15 l/min. Recovery indices were compared using unpaired t-tests and ANOVA. Prior to extubation, minute ventilation and end-tidal CO2 in hypercapnic hyperpnoea and control groups were 10.3 ± 1.7 l/min vs. 5.4 ± 1.2 l/min (P < 0.001) and 6.6 ± 0.6 kPa and 5.2 ± 0.5 kPa (P < 0.001), respectively. Compared to control, the study group had shorter time to extubation [4.4 ± 1.3 (SD) vs. 9.8 ± 4.4 min, P < 0.01], BIS recovery to > 75 (2.4 ± 0.9 vs. 6.1 ± 3.1 min, P < 0.01), eye opening (3.9 ± 1.6 vs. 9.8 ± 6.2 min, P < 0.01), eligibility for leaving operating room (5.1 ± 1.2 vs. 11.1 ± 4.6 min, P < 0.01), and post-anaesthesia care unit (73.9 ± 14.2 vs. 89.4 ± 22.6) Hypercapnic hyperpnoea in spontaneously breathing patients halves the time of recovery from sevoflurane-induced anaesthesia in the operating room.

Arterial carbon dioxide tension and outcome in patients admitted to the intensive care unit after cardiac arrest

BackgroundArterial carbon dioxide tension (PaCO2) affects neuronal function and cerebral blood flow. However, its association with outcome in patients admitted to intensive care unit (ICU) after cardiac arrest (CA) has not been evaluated. Methods and resultsObservational cohort study using data from the Australian New Zealand (ANZ) Intensive Care Society Adult-Patient-Database (ANZICS-APD). Outcomes analyses were adjusted for illness severity, co-morbidities, hypothermia, treatment limitations, age, year of admission, glucose, source of admission, PaO2 and propensity score.We studied 16,542 consecutive patients admitted to 125 ANZ ICUs after CA between 2000 and 2011. Using the APD-PaCO2 (obtained within 24h of ICU admission), 3010 (18.2%) were classified into the hypo- (PaCO2<35mmHg), 6705 (40.5%) into the normo- (35–45mmHg) and 6827 (41.3%) into the hypercapnia (>45mmHg) group. The hypocapnia group, compared with the normocapnia group, had a trend toward higher in-hospital mortality (OR 1.12 [95% CI 1.00–1.24, p=0.04]), lower rate of discharge home (OR 0.81 [0.70–0.94, p<0.01]) and higher likelihood of fulfilling composite adverse outcome of death and no discharge home (OR 1.23 [1.10–1.37, p<0.001]). In contrast, the hypercapnia group had similar in-hospital mortality (OR 1.06 [0.97–1.15, p=0.19]) but higher rate of discharge home among survivors (OR 1.16 [1.03–1.32, p=0.01]) and similar likelihood of fulfilling the composite outcome (OR 0.97 [0.89–1.06, p=0.52]). Cox-proportional hazards modelling supported these findings. ConclusionsHypo- and hypercapnia are common after ICU admission post-CA. Compared with normocapnia, hypocapnia was independently associated with worse clinical outcomes and hypercapnia a greater likelihood of discharge home among survivors.

A study on sleep architecture in patients with chronic respiratory failure under long-term oxygen therapy—Focused on the influence of ventilatory failure (high CO&amp;lt;sub&amp;gt;2&amp;lt;/sub&amp;gt;) elements on the patient’s sleep architecture

Sleep disturbance related symptoms are common in patients with long-term oxygen therapy (LTOT). Essentially, there were only few previous reports about the sleep architecture in patients with respiratory disease, such as chronic obstructive pulmonary disease (COPD). This study aims to clarify the objective sleep state and the elements that affect sleep architecture in Chronic Respiratory Failure (CRF) patients with focus on clinical cases of chronic hypercapnia. 13 subjects with chronic respiratory failure were enrolled in the study. All the subjects were pre-evaluated by pulmonary function test and Arterial blood gas analysis (ABG) including exercise testing. Polysomnography (PSG) test was performed in each subject with supplemental oxygen. The estimated base line PaCO2 value that reflects overall PaCO2 including sleep period was calculated using equation of PaCO2[2.4×(HCOˉ3)-22]from obtained ABG value just before PSG test. 6 subjects were classified as hypercapnic group (base line PaCO2 ≥ 45 mmHg) and 7 subjects were non-hypercapnic group (base line PaCO2 2 were no significant difference. This study suggests that patients with estimated hypercapnia had more disturbed sleep architecture especially significant loss of sleep latency than non-hypercapnic patient with chronic respiratory failure under LTOT. Nocturnal PaCO2 level or ventilatory function may contribute to sleep disturbance in patients with estimated hypercapnia during LTOT.

Moderate and prolonged hypercapnic acidosis may protect against ventilator-induced diaphragmatic dysfunction in healthy piglet: an in vivo study

IntroductionProtective ventilation by using limited airway pressures and ventilation may result in moderate and prolonged hypercapnic acidosis, as often observed in critically ill patients. Because allowing moderate and prolonged hypercapnia may be considered protective measure for the lungs, we hypothesized that moderate and prolonged hypercapnic acidosis may protect the diaphragm against ventilator-induced diaphragmatic dysfunction (VIDD). The aim of our study was to evaluate the effects of moderate and prolonged (72 hours of mechanical ventilation) hypercapnic acidosis on in vivo diaphragmatic function.MethodsTwo groups of anesthetized piglets were ventilated during a 72-hour period. Piglets were assigned to the Normocapnia group (n = 6), ventilated in normocapnia, or to the Hypercapnia group (n = 6), ventilated with moderate hypercapnic acidosis (PaCO2 from 55 to 70 mm Hg) during the 72-hour period of the study. Every 12 hours, we measured transdiaphragmatic pressure (Pdi) after bilateral, supramaximal transjugular stimulation of the two phrenic nerves to assess in vivo diaphragmatic contractile force. Pressure/frequency curves were drawn after stimulation from 20 to 120 Hz of the phrenic nerves. The protocol was approved by our institutional animal-care committee.ResultsModerate and prolonged hypercapnic acidosis was well tolerated during the study period. The baseline pressure/frequency curves of the two groups were not significantly different (Pdi at 20 Hz, 32.7 ± 8.7 cm H2O, versus 34.4 ± 8.4 cm H2O; and at 120 Hz, 56.8 ± 8.7 cm H2O versus 60.8 ± 5.7 cm H2O, for Normocapnia and Hypercapnia groups, respectively). After 72 hours of ventilation, Pdi decreased by 25% of its baseline value in the Normocapnia group, whereas Pdi did not decrease in the Hypercapnia group.ConclusionsModerate and prolonged hypercapnic acidosis limited the occurrence of VIDD during controlled mechanical ventilation in a healthy piglet model. Consequences of moderate and prolonged hypercapnic acidosis should be better explored with further studies before being tested on patients.

Hypercapnic acidosis transiently weakens hypoxic pulmonary vasoconstriction without affecting endogenous pulmonary nitric oxide production

Hypercapnic acidosis often occurs in critically ill patients and during protective mechanical ventilation; however, the effect of hypercapnic acidosis on endogenous nitric oxide (NO) production and hypoxic pulmonary vasoconstriction (HPV) presents conflicting results. The aim of this study is to test the hypothesis that hypercapnic acidosis augments HPV without changing endogenous NO production in both hyperoxic and hypoxic lung regions in pigs. Sixteen healthy anesthetized pigs were separately ventilated with hypoxic gas to the left lower lobe (LLL) and hyperoxic gas to the rest of the lung. Eight pigs received 10% carbon dioxide (CO(2)) inhalation to both lung regions (hypercapnia group), and eight pigs formed the control group. NO concentration in exhaled air (ENO), nitric oxide synthase (NOS) activity, cyclic guanosine monophosphate (cGMP) in lung tissue, and regional pulmonary blood flow were measured. There were no differences between the groups for ENO, Ca(2+)-independent or Ca(2+)-dependent NOS activity, or cGMP in hypoxic or hyperoxic lung regions. Relative perfusion to LLL (Q (LLL)/Q (T)) was reduced similarly in both groups when LLL hypoxia was induced. During the first 90 min of hypercapnia, Q (LLL)/Q (T) increased from 6% (1%) [mean (standard deviation, SD)] to 9% (2%) (p < 0.01), and then decreased to the same level as the control group, where Q (LLL)/Q (T) remained unchanged. Cardiac output increased during hypercapnia (p < 0.01), resulting in increased oxygen delivery (p < 0.01), despite decreased PaO(2) (p < 0.01)(.) Hypercapnic acidosis does not potentiate HPV, but rather transiently weakens HPV, and does not affect endogenous NO production in either hypoxic or hyperoxic lung regions.

Effect of therapeutic hypercapnia on hepatic ischemia-reperfusion injury in rat liver transplantation

Objective To investigate the effect of therapeutic hypercapnia on hepatic ischemia-reperfusion (I/R) injury in rat liver transplantation.Methods Male specific pathogen-free adult Wistar rats aged 6 weeks weighing 220-280 g were used in this study.Sixteen rats in which liver transplantation was successfully performed were randomly divided into 2 groups ( n =8 each): liver transplantation group (group LT) and therapeutic hypercapnia group (group TH).In group TH,PaCO2 was maintained at 80-100 mm Hg by inhalation of CO2 for 1 h at the begining of reperfusion.MAP,PaO2 and PaCO2 was recorded during reperfusion.Blood samples were obtained at 2 h of reperfusion for determination of serum ALT,AST,TNF-α,IL-1 and IL-6 levels,and then the rats were sacrificed and transplanted liver was immediately removed for determination of NF-κB activity and apoptosis and microscopic examination.The apoptotic index was calculated.Results MAP,PaO2 and PaCO2 were higher,and serum ALT,AST,TNF-α,IL-1 and IL-6 levels,NF-κB activity and apoptotic index lower in group TH than in group LT ( P ＜ 0.05).The histopathologic damage was ameliorated in group TH as compared with group LT.Conclusion Therapeutic hypercapnia can attenuate hepatic I/R injury in rat liver transplantation by inhibiting inflammatory response and apoptosis. Key words: Hypercapnia; Liver transplantation; Reperfusion injury

582 Change in myocardial oxygenation during mild hypo- and hypercapnia: A blood oxygen level dependent cardiovascular magnetic resonance (BOLD-CMR) study in healthy volunteers

BOLD-CMR uses de-oxygenated hemoglobin (Hb) as an endogenous contrast. The signal intensity (SI) is determined by the amount of de-oxygenated Hb, blood volume and blood flow. The aim of this study was to investigate whether BOLD-CMR can detect changes in myocardial oxygenation during mild hypo- and hypercapnia in healthy individuals. Fifteen healthy volunteers were scanned with a BOLD sensitive modified SSFP cine sequence on a clinical 1.5T scanner (hypocapnia n = 8, hypercapnia n = 7). Continuous BOLD cines were acquired during 1 min of apnea in the hypercapnic group, whereas images were acquired prior to and post 1 min of hyperventilation in the hypocapnic group. SI was measured and averaged over all phases of the cardiac cycle, and also averaged between two acquisitions before and again after the breath hold. Immediately before and after image acquisition capillary blood gases were measured. One subject was excluded in the hypocapnia group due to motion artifacts. The hypocapnia groups showed a mean SI drop of 6.1% (P < 0.001, n = 7) after 1 min of hyperventilation (fig. 1a) while a mean SI increase of 7.1% (P < 0.001, n = 7) was observed over 1 min of apnea (fig. 1b). PCO2 dropped significantly from 27.9 ± 4.1 mmHg to 22.0 ± 3.2 mmHg (P = 0.02) after hyperventilation. Although there was a slight increase in PCO2 post breath-hold, it was not significant. PO2 did not change in either group. Our data suggest that BOLD-CMR can detect changes of myocardial oxygenation related to vasoconstriction/vasodilatation during hypo- and hypercapnia.

Investigation of pulmonary hemodynamics and chest X-ray findings in hypercapnic patients with pulmonary tuberculosis sequelae

We investigated pulmonary hemodynamics and chest X-ray findings to explore pathophysiological significance of chronic hypercapnia in patients with pulmonary tuberculosis sequelae. One hundred and seven patients underwent examinations of blood gases and right cardiac catheterization. The patients were divided into two groups, according to arterial carbon dioxide tension under room air breathing (PaCO2). Group I (n = 35) was defined as 45 Torr or lower of PaCO2, and Group II (n = 72) was the hypercapnic group whose PaCO2 was over 45 Torr. In addition, spirometry was done in 34 patients of Group I and 68 of Group II. First, the values of blood gases, spirometry and pulmonary hemodynamics were compared between the two groups. Secondly, between 22 of Group I and 50 of Group II, the values of pulmonary arteriolar resistance (PAR) before and after 100% oxygen breathing for 10 minutes were compared. These comparisons were made by exploratory data analysis. Lastly, we described in all cases with five items of chest X-ray findings and the extent of each finding we had defined. The items were emphysematous change; fibrosis, bronchiectasis, and/or cavity (hereafter abbreviated as "fibrosis"); lung resection and/or atelectasis; pleural thickening; and thoracoplasty. We explored the items of X-ray findings which may relate to hypercapnia by ridit (abbreviation for "relative to an identified distribution") analysis. The results were as follows. (1) Hypercapnic patients tended to have severer restrictive ventilatory impairment and hypoxemia. Under an even level of arterial oxygen tension (PaO2), tissue oxygenation was not poorer in Group II than in Group I. (2) Hypercapnic patients tended to have more unfavorable pulmonary hemodynamics. More than half of them had pulmonary hypertension defined as 20 mmHg or higher of pulmonary artery mean pressure (PAm). Under an even level of PaO2, PAm was higher in Group II. Although 34 patients of Group II showed PaO2 over 60 Torr, 23 of them had pulmonary hypertension. (3) PAR after oxygen breathing was more likely to decrease in Group II than in Group I. (4) As any mean ridit was standardized and adjusted to 0.5 in Group I, the maximum was the mean ridit of "pleural thickening" (= 0.67), next "fibrosis" (= 0.65) in Group II. The above two items of X-ray findings, in which each mean ridit was higher than in any other item, were more influential on hypercapnia. We conclude as follows. (1) Pulmonary hypertension is severer in hypercapnic patients with pulmonary tuberculosis sequelae; it may be mainly attributable to hypoxic pulmonary vasoconstriction. (2) An important cause of chronic hypercapnia may be pathological changes such as "pleural thickening" and "fibrosis" seen on the radiogram.

Tuberculosis sequelae in Japan

Tuberculosis had been the leading cause of death in Japan until 1950, and in these days there were about 3 million patients with active tuberculosis every year. From about 1950 to 1960 surgery was the treatment of choice if there were cavities and the lesions were regional. The number of patients who had thoracoplasties and/or pulmonary resections at national sanatoriums during the period of 1954 to 1961 was about 200,000. Since national sanatoriums had about 25% of the total beds for tuberculosis in Japan at that time, the total number of surgically treated patients would be around four times this number, that is 0.8 to 1.0 million. Many of those who survived suffered later from complications, which included chronic respiratory failures, chronic hepatitis (hepatitis C), liver cirrhosis and/or hepatic cell carcinomas. There are at least 50,000 patients who are under home oxygen therapy (HOT) in Japan, of whom about 30% are those with pulmonary tuberculosis sequelae (TBS). The survival rate after the start of HOT in these patients was found better in those who had surgical treatments than in those who had medical treatments only. Since hypercapnea was more common in the former, better survival rates in the hypercapnic than in the normocapnic patients with TBS as a whole could be due to the fact that more of the surgically treated patients were included in the hypercapnic group. For this reason, it is premature to conclude that hypercapnea is an independent favorable prognostic factor in TBS patients with chronic respiratory failure. Because more than one-forth of thoracoplasties and/or pulmonary resections were done in national sanatoriums, it is the responsibility of those who are now working in national hospitals to treat and support these patients with TBS who developed complications such as respiratory failures, chronic hepatitis, liver cirrhosis, and/or hepatic cell carcinomas.

Effect of therapeutic hypercapnia on type I alveolar cells in transplanted lung in rats

Objective To investigate the effects of therapeutic hypercapnia on type Ⅱ alveolar cells (ATⅡ ) in the transplanted lung in rats.Methods Twenty-eight pathogen free adult male Wistar rats weighing 180-220 g were randomly divided into 2 groups (n= 14 each) : control group (group C) and therapeutic hypercapnia group (group T). The animals were anesthetized with intraperitoneal 3% pentobarbital 30 mg/kg, tracheostomized and mechanically ventilated with 50% O2-50% N2 (VT 10 ml/kg, RR 60 bpm, I∶ E1∶1). Left lung transplantation was performed. In group T starting from the beginning of reperiusion of the transplanted lung, the animals were ventilated with a mixture of 50% O2-N2 and C02(in appropriate concentrations) to keep PaCO2 between 80-100 mm Hg. After 90 min of reperfusion of the transplanted lung, blood samples were collected from pulmonary vein of the transplanted lung and blood gas analysis was performed. Oxygenation index was calculated.AT II cells were isolated from the transplanted lung and purified and examined with electronic microscope. The apoptosis rate of AT Ⅱ cells was detected by flow cytometry. Results Oxygenation index was significantly higher, the apoptotic rate of ATⅡ cells lower, the damage to ATⅡ cells was less in group T than in group C.Conclusion Therapeutic hypercapnia can protect the AT Ⅱ cells in the transplanted lung and improve the function of the trans planted lung. Key words: Hypercapnia; Lung transplantation; Pulmonary alveoli; Epithelial cells

Open Lung Strategy in a Lamb Model of Respiratory Distress Syndrome

We tested the hypothesis that an open lung strategy with recruitment maneuvers will improve oxygenation and decrease lung injury in comparison with a permissive hypercapnia strategy in preterm lambs. Preterm lambs born by operative delivery at 131 ± 1 days of gestational age (term = 150 days) were randomized to an open lung group (OLG, n = 5) or a permissive hypercapnia group (PHG, n = 4). In the OLG, ramp recruitment maneuvers were performed by increasing and then decreasing peak inspiratory pressure and positive end-expiratory pressure (adjusting for expiratory tidal volume [V(T)] 6 to 8 mL/kg). In the PHG, lambs received ventilation with V(T) of 6 to 8 mL/kg, adapting pressures and respiratory rate according to arterial blood gases results. Fraction of inspired oxygen was adjusted for oxygen saturation 88 to 93%. Lambs were ventilated for 6 hours. Lung pathology was assessed by masked examiners. There were no significant differences for arterial to alveolar oxygen tension ratio, partial pressure of arterial carbon dioxide, blood pressure, compliance, resistance, and other variables between groups. Gas leaks were noted in four of five lambs in the OLG and one of four in the PHG (relative risk 3.2; 95% confidence interval 0.5 to 18). By histological examination, lung areas were overdistended (49% in the OLG, 37% in the PHG). Open lung ventilation following ramp recruitment maneuvers did not offer advantages and might increase lung injury compared with a permissive hypercapnia strategy in preterm lambs with lung immaturity.

The effect of early prenatal hypercapnia on the vascular network in the chorioallantoic membrane of the chicken embryo

Over the last decade, the poultry sector has sought to develop novel ways to monitor chicken embryonic growth, health, and quality to control and optimize egg incubation conditions, particularly the concentration of dissolved gases (O(2), CO(2)). One of the parameters, which may change under different gas concentrations, is the angiogenesis in the chorioallantoic membrane (CAM), the organ for gas exchange of the chicken embryo. In this study, a newly developed methodology was used to quantify the angiogenesis in the CAM under normal and early hypercapnic conditions (i.e., increased CO(2) concentrations). Two experiments were conducted in which the same CO(2) profile was applied. The development of the vascular system was monitored from embryonic day (ED) 10 until ED 14 in Experiment 1, and until ED 16 in Experiment 2. This development was characterized by two different parameters-the vascular fraction (VF) as a measure for the density of the vascular network and the fractal dimension (FD) as a measure for the degree of branching of the vascular network. Moreover, in Experiment 2, embryo weights were compared between both groups. The proposed methodology showed that differences in the development of the vascular system could be observed across groups but also as function of the ED. Both VF and FD and the embryo weights were shown to be higher in the hypercapnia group compared to the control group.

Coping strategy and stress response of European sea bass Dicentrarchus labrax to acute and chronic environmental hypercapnia under hyperoxic conditions

Four groups of sea bass Dicentrarchus labrax (202 ± 42 g, mean weight ± SD) kept in a recycling system were exposed for 45 days to four different levels of water carbon dioxide partial pressure (PCO 2): 2 mm Hg (2.8 mg/l; control), 13.9 mm Hg (16.9 mg/l; low), 24.7 mm Hg (32.8 mg/l; medium) and 37.8 mm Hg (51.2 mg/l; high). Mean water oxygen saturation was 136–137%. Blood gas status, acid–base balance and stress response were measured during acute (0, 3, 6, 24, 48 and 96 h) and chronic (8, 22, and 45 days) exposure. Blood PCO 2, [tCO 2] and pH significantly increased in hypercapnic groups according to water CO 2 concentrations and were significantly higher compared to control groups throughout the trial. Blood pH increase was due to blood HCO 3 − accumulation followed by Cl − loss. Blood PO 2 significantly decreased in all hypercapnic groups compared to controls during both acute and chronic exposure. Htc and tHb increased during acute exposure in response to environmental hypercapnia and significantly decreased at the end of the trial in high CO 2 groups. Serum cortisol increased significantly during acute exposure as a function of time and CO 2, resulting in higher values in medium and high CO 2 groups compared to low and control groups. Cortisol levels did not change during the chronic phase in relation to CO 2 and no differences were observed among groups after 45 days. Serum glucose increased significantly in high hypercapnic groups after 8 days. Serum osmolality, [Na +] and [K +] did not differ among hypercapnic and control groups during the trial. A significant positive correlation was found between reactive oxygen metabolites (ROMs) and total antioxidant status (AOP) but neither parameter changed versus CO 2 concentration. No significant differences in growth performance (body weight, standard length, condition factor and specific growth rate) were observed between controls and hypercapnic groups. Mortality was found to be negligible (< 1.6%) in all groups. Sea bass displayed fast and efficient acid–base compensatory mechanisms in response to environmental hypercapnia up to 38 mm Hg PCO 2. However, acute and chronic exposure above 25 mm Hg PCO 2 (> 30 mg/l CO 2) was found to be stressful, potentially impairing the welfare of sea bass.

S67 Phenotypic differences between obese patients with eucapnic and hypercapnic sleep-disordered breathing (SDB)

BackgroundObesity-related SDB requiring domiciliary non-invasive ventilation (NIV) can present as (1) eucapnic obstructive sleep apnoea (OSA) (2) hypercapnic OSA (PaCO2 >6 kPa) (3) hypercapnic OSA with obesity hypoventilation syndrome (OHS)...

Effects of hypercapnia on the electroretinogram in sevoflurane and isoflurane anaesthetized dogs

To evaluate the effects of induced hypercapnia on the electroretinogram (ERG) in beagle dogs anaesthetized with isoflurane and sevoflurane. Binocular, full-field flash photopic and scotopic ERGs were obtained from six healthy neutered female beagle dogs. In order to determine Vmax and the photopic negative response (PhNR), photopic ERG luminance-response curves were generated with 17 different light stimuli. Photopic flicker ERGs were obtained at 30-Hz temporal frequency. Scotopic ERGs were recorded after 35 min of dark adaptation. For all animals, this procedure was performed once in four different sessions: isoflurane + end-tidal [CO(2)] at 35 mmHg +/- 3 mmHg (ISON), isoflurane + end-tidal [CO(2)] at 65 mmHg +/- 3 mmHg (ISOH), sevoflurane + end-tidal [CO(2)] at 35 mmHg +/- 3 mmHg (SEVON), isoflurane + end-tidal [CO(2)] at 65 mmHg +/- 3 mmHg (SEVOH). In photopic conditions, b-wave amplitudes were significantly smaller in hypercapnic groups (ISON = 170.6 +/- 12.1 microV; ISOH = 132.6 +/- 24.9 microV; SEVON = 170.9 +/- 14.4 microV; SEVOH = 130.2 +/- 22.8 microV). Similarly, in scotopic conditions, b-wave amplitudes were significantly decreased when CO(2) was increased (ISON = 89.4 +/- 14.7 microV; ISOH = 58.2 +/- 17.6 microV; SEVON = 93.4 +/- 24.1 microV; SEVOH = 56.2 +/- 22.2 microV). Flicker peak times were significantly increased in hypercapnic groups (ISON = 25.9 +/- 0.4 ms; ISOH = 27.7 +/- 1.2 ms; SEVON = 25.9 +/- 1.5 ms; SEVOH = 27.2 +/- 0.7 ms). Our results clearly indicate that induced hypercapnia significantly alters the genesis of the electroretinogram at level of ON-pathway and suggest that OFF-pathway is unaffected and that ERGs obtained from isoflurane or sevoflurane anaesthetized dogs are almost identical. Control of hypercapnia must be taken into consideration when ERGs are performed under inhaled anaesthesia in dogs.

Effect of Chronic Hypoxic Hypercapnia on the Expression of Bcl-2 and Bax Genes and Apoptosis in Rat Hippocampal Neurons

The objective of this paper is to explore the effect of chronic hypoxic hypercapnia on the apoptosis of rat neural cells in the hippocampus, as well as the relationship between apoptosis and Bcl-2 and Bax gene expression. In this study, 50 male Sprague-Dawley rats were randomly divided into 5 groups: a normal control group, and 4 hypoxic hypercapnia groups which received hypoxic hypercapnia treatment for 1, 2 , 3 and 4 weeks. The in situ apoptosis in the hippocampus was detected by TUNEL staining. The expression of bcl-2 and bax mRNA in the hippocampus was examined by RT-PCR. Results showed that the apoptosis index (AI) and expression of Bax mRNA increased with the duration of hypoxic hypercapnia, and that the expression of Bcl-2 mRNA increased at the beginning but then declined. There was a significant positive correlation between AI and the expression of Bax mRNA (r = 0.814, p < 0.01), and there was a significant negative correlation between AI and the ratio of Bcl-2 mRNA/Bax mRNA (r = –0.405, p < 0.01). The results suggest that apoptosis can be induced by chronic hypoxic hypercapnia in the rat hippocampus. The ratio of Bcl-2/Bax declined gradually, which accelerates the occurrence of apoptosis.

Effect of therapeutic hypercapnia on inflammatory response in rat lung transplantation

Objective To investigate the effect of therapeutic hypercapnia on the inflammatory response in the rat lung transplantation. Methods Male pathogen free Wistar rats weighing 300-400 g were used in this study. The animals were anesthetized with 3% pentobarbital sodium 30 mg/kg, tracheostomized and mechanically ventilated (V_T 10 ml/kg, RR 50 bpm, FiO_2 50%). Carotid artery and femoral vein were cannulated for BP monitoring, blood sampling and fluid and drug administration. Left lung transplantation was performed using modified cuff technique. Forty-eight animals in which lung transplantation was successfully performed were randomized into 2 groups ( n = 24 each) : model group (M) and hypercapnia group (H) . In group H, PaCO_2 was maintained at 80-100 mm Hg by inhalation of CO_2.Arterial blood samples were obtained before lung transplantation (To , baseline) and at 1, 2, 4 h (T_(1-3)) of reperfusion for determination of blood TNF-α, IL-1 and IL-8 concentrations. The animals were then killed and the transplanted lungs were removed for microscopic examination and calculation of wet/dry lung weight ratio. Results The MAP and PaO_2 were significantly higher in group H than in group M. The blood IL-8 and TNF-α concentrations were significantly lower at T_(1-3) in group H than in group M, but there was no significant difference in blood IL-1 concentration between the 2 groups. The elastase content in the lung tissue was significantly lower at T_2 and T_3 in group H than in group M. Microscopic examination showed that the alveolar hemorrhage, the infiltration of the lung by macrophages and neutrophils and lung edema were significantly less in group H than in group M. Conclusion Therapeutic hypercapnia can obviously inhibit the inflammatory response in the rat lung transplantation. Key words: Hypercapnia; Lung transplantation; Reperfusion injury; Inflammation

Influence of hypercapnia on cardiovascular responses to tracheal intubation

Background Laryngoscopy and tracheal intubation are often associated with tachycardia, hypertension, and arrhythmias. There is a risk of hypercapnia in the case of difficult mask ventilation. The circulatory response to hypercapnia is increases in arterial pressure and heart rate. We evaluated the difference of cardiovascular responses to tracheal intubation between normocapnia and hypercapnia during mask ventilation before tracheal intubation. Methods We studied 40 ASA physical status I to II patients under general anesthesia. Induction of anesthesia was achieved with midazolam 0.05 mg/kg, propofol 1.5 mg/kg, alfentanil 10 μg/kg, and rocuronium 0.6 mg/kg IV. The lungs were mechanically ventilated with a tidal volume of 10 mL/kg and 6 to 10 bpm in the hypercapnia group (n = 20) or 12 to 15 bpm in the normocapnia group (n = 20) during the induction period. Intubation was performed 3 minutes after the induction, and anesthesia was maintained using 1.5% sevoflurane (inspired) and 75% N 2O in oxygen. Heart rate, systolic arterial pressure (SAP), and diastolic arterial pressure were recorded every minute throughout the study. Results The proportion of the patients whose increase of SAP between just before intubation and 1 minute after intubation was more than 30 mm Hg in the hypercapnia group (40%) was greater than that in the normocapnia group (9.5%) ( P = .0325). There were no differences in heart rate and diastolic arterial pressure between hypercapnia and normocapnia groups. For the SAP of the patients, the trend of changes was increased ( P = .024). Conclusions Hypercapnia during mask ventilation before tracheal intubation may exaggerate the increase of SAP during intubation compared to normocapnia. Ventilation was important in minimizing hemodynamic responses during induction regardless of using drugs.