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Background: Paediatric convulsive status epilepticus is the most common neurological emergency presenting to emergency departments. Risks of resultant neurological morbidity and mortality increase with seizure duration. If the seizure fails to stop within defined time-windows, standard care follows an algorithm of stepwise escalation to more intensive treatments, ultimately resorting to induction of general anaesthesia and ventilation. Additionally, ventilatory support may also be required to treat respiratory depression, a common unwanted effect of treatment. There is strong pre-clinical evidence that pH (acid-base balance) is an important determinant of seizure commencement and cessation, with seizures tending to start under alkaline conditions and terminate under acidic conditions. These mechanisms may be particularly important in febrile status epilepticus: prolonged fever-related seizures which predominantly affect very young children. This trial will assess whether imposition of mild respiratory acidosis by manipulation of inhaled medical gas improves response rates to first-line medical treatment., Methods: A double-blind, placebo-controlled trial of pH manipulation as an adjunct to standard medical treatment of convulsive status epilepticus in children. The control arm receives standard medical management whilst inhaling 100% oxygen; the active arm receives standard medical management whilst inhaling a commercially available mixture of 95% oxygen, 5% carbon dioxide known as 'carbogen'. Due to the urgent need to treat the seizure, deferred consent is used. The primary outcome is success of first-line treatment in seizure cessation. Planned subgroup analyses will be undertaken for febrile and non-febrile seizures. Secondary outcomes include rates of induction of general anaesthesia, admission to intensive care, adverse events, and 30-day mortality., Discussion: If safe and effective 95% oxygen, 5% carbon dioxide may be an important adjunct in the management of convulsive status epilepticus with potential for pre-hospital use by paramedics, families, and school staff., Trial Registration: EudraCT: 2021-005367-49. CTA: 17136/0300/001., Isrctn: 52731862. Registered on July 2022., (© 2024. The Author(s).)

Aquatic CO 2 tensions may exceed 30-60 Torr (ca. 30,000-79,000 μatm, respectively; hypercarbia) in some environments inducing severe acid-base challenges in fish. Typically, during exposure to hypercarbia blood pH (pH e ) is initially reduced and then compensated in association with an increase in plasma HCO 3 - in exchange for Cl - . Typically, intracellular pH (pH i ) is reduced and recovery is to some degree coupled to pH e recovery (coupled pH regulation). However, during acute hypercarbia, pH e recovery has been proposed to be limited by an "apparent upper bicarbonate threshold", restricting complete pH e recovery to below 15 Torr PCO 2 . At PCO 2 values beyond that which fish can compensate pH e , some fish are able to fully protect pH i despite large sustained reductions in pH e (preferential pH i regulation) and can tolerate PCO 2  > 45 Torr. This review discusses pH e and pH i regulation during exposure to hypercarbia starting with modeling the capacity and theoretical limit to pH e compensation in 19 studies. Next, we discuss how fish compensate severe acute hypercarbia exposures beyond the putative limit of pH e compensation using preferential pH i regulation which has recently been observed to be common among fish subjected to severe hypercarbia. Finally, we consider the evolution of pH regulatory strategies in vertebrates, including how the presence of preferential pH i regulation in embryonic reptiles may indicate that it is an embryonic trait that is either lost or retained in adult vertebrates and may have served as an exaptation for key evolutionary transitions during vertebrate evolution., (Crown Copyright © 2019. Published by Elsevier Inc. All rights reserved.)

Marine crabs inhabit shallow coastal/estuarine habitats particularly sensitive to climate change, and yet we know very little about the diversity of their responses to environmental change. We report the effects of a rarely studied, but increasingly prevalent, combination of environmental factors, that of near-future pCO 2 (~1000 µatm) and a physiologically relevant 20% reduction in salinity. We focused on two crab species with differing abilities to cope with natural salinity change, and revealed via physiological and molecular studies that salinity had an overriding effect on ion exchange in the osmoregulating shore crab, Carcinus maenas. This species was unaffected by elevated CO 2 , and was able to hyper-osmoregulate and maintain haemolymph pH homeostasis for at least one year. By contrast, the commercially important edible crab, Cancer pagurus, an osmoconformer, had limited ion-transporting capacities, which were unresponsive to dilute seawater. Elevated CO 2 disrupted haemolymph pH homeostasis, but there was some respite in dilute seawater due to a salinity-induced metabolic alkalosis (increase in HCO 3 - at constant pCO 2 ). Ultimately, Cancer pagurus was poorly equipped to compensate for change, and exposures were limited to 9 months. Failure to understand the full spectrum of species-related vulnerabilities could lead to erroneous predictions of the impacts of a changing marine climate.

Multiple environmental stressors may interact in complex ways to exceed or diminish the impacts of individual stressors. In the present study, the interactive effects of two ecologically relevant stressors [increased temperature and partial pressure of carbon dioxide (Pco 2 )] were assessed for freshwater mussels, a group of organisms that are among the most sensitive and rapidly declining worldwide. The individual and combined effects of elevated temperature (22°C-34°C) and Pco 2 (~230, 58,000 µatm) on juvenile Lampsilis siliquoidea were quantified over a 5- or 14-day period, during which physiological and whole animal responses were measured. Exposure to elevated temperature induced a series of physiological responses, including an increase in oxygen consumption rates following 5 days of exposure at 31°C and an increase in carbonic anhydrase ( ca) and heat shock protein 70 mRNA levels following 14 days of exposure at 28°C and 34°C, respectively. Treatment with elevated Pco 2 activated acid-base regulatory responses including increases in CA and Na + -K + -ATPase activity and a novel mechanism for acid-base regulation during Pco 2 exposure in freshwater mussels was proposed. Thermal and CO 2 stressors also interacted such that responses to the thermal stressor were diminished in mussels exposed to elevated Pco 2 , resulting in the greatest level of mortality. Additionally, larger mussels were more likely to survive treatment with elevated Pco 2 and/or temperature. Together, exposure to elevated Pco 2 may compromise the ability of juvenile freshwater mussels to respond to additional stressors, such as increased temperatures, highlighting the importance of considering not only the individual but also the interactive effects of multiple environmental stressors.

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., (Copyright © 2015 Elsevier B.V. All rights reserved.)

The aim of this study was to compare physiological responses in Siberian sturgeon (Acipenser baeri) induced by propofol and CO2 anaesthesia. Two procedures were applied during the experiment. In procedure I, blood samples were collected immediately after exposure (1, 2, 5, 10 min) to the anaesthetic. In procedure II, fish were exposed to the anaesthetic for 10 minutes and then were moved to anaesthetic free water. Blood was sampled after 5, 10, 20 or 30 min of recovery time. Gasometrical and biochemical analyses were performed on collected blood. In CO2 anaesthetized fish strong hypercapnic acidosis was revealed. The drop of the HCO3-/CO2 ratio, from 28:1 in control fish up to 4:1 in CO2 anaesthetized ones, proved that the compensation mechanism is not capable of preventing acidosis during CO2 anaesthesia in Siberian sturgeon. In contrast, only moderate, respiratory acidosis occurred in sturgeons anaesthetised with propofol. Hypercapnic acidosis during CO2 anaesthesia was followed by a fourfold increase of ammonia level in the blood. Glucose level, increasing only during recovery time, indicates that a secondary stress response occurred when awareness of anaesthetized fish had been restored.

CO2 exposure elicits multiple changes in the acid-base balance and hematology of avian embryos, but the time-specific, dose-dependent effects of graded increases in extrinsic CO2 in a normoxic environment are poorly understood. Consequently, we exposed day 15 chicken embryos to 1, 3, 5, 6 or 10% CO2 in 20% O2. We hypothesized that both the magnitude of hypercapnic respiratory acidosis and the resultant metabolic compensation within 24 h of exposure to <10% CO2 are proportional to ambient CO2 concentration ([CO2]). We also predicted that regulation of hematological respiratory variables is graded according to [CO2]. Time-course (2, 6 and 24 h) changes were determined for acid-base disturbances and hematological respiratory variables; hematocrit (Hct), red blood cell concentration ([RBC]), hemoglobin concentration, mean corpuscular volume (MCV) and other mean corpuscular indices. Both the decrease in uncompensated pH, which indicates uncompensated respiratory acidosis, and the compensatory pH increase, a sign of metabolic compensation, increased with [CO2]. The partial metabolic compensation across all CO2 gas mixtures was ~17, 46 and 53% compensation at 2, 6 and 24 h, respectively. Hematological responses were nearly identical across the entire range of [CO2], with Hct decreasing across the time course of CO2 exposure due to a decrease in MCV from 2 to 24 h and a decrease in [RBC] at 24 h. Even though hematological regulation was not graded, chicken embryos were able to compensate and survive exposure to <10% CO2.

Objective: Systemic effects of carbon dioxide (CO2) insufflation during left-sided cardiac surgery were evaluated in a prospective randomized study, with regard to acid-base status, gas exchange, cerebral hemodynamics, and red blood cell morphology., Methods: Twenty patients undergoing elective left-sided cardiac surgery were randomized to de-airing procedure either by CO2 insufflation technique (CO2 group, n = 10) or by Lund technique without CO2 insufflation (Lund group, n = 10). Groups underwent assessment of acid-base status by intermittent arterial blood gases and in-line blood gas monitoring. Capnography was used to determine volume of CO2 produced. Cerebral hemodynamics was measured by transcranial Doppler sonography and near-infrared spectroscopy. Red cell morphology from cardiotomy suction and vent tubing was studied by scanning electron microscopy., Results: Patients in the CO2 group consequently developed significantly higher levels of hypercapnia with a concomitant increase in the volume of CO2 produced despite significantly higher oxygenator gas flows compared with the Lund group. Effects on cerebral hemodynamics were observed in the CO2 group with significantly higher blood flow velocities in the middle cerebral artery and higher regional cerebral saturation. Red blood cell damage was observed in the CO2 group by scanning electron microscopy (97% in CO2 group vs 18% in Lund group)., Conclusions: Insufflation of CO2 into the cardiothoracic wound cavity during left-sided cardiac surgery can induce hypercapnic acidosis and increased cerebral blood flow and local blood cell damage. These systemic effects should be monitored by in-line capnography and acid-base measurements for early and effective correction by increase in gas flows to the oxygenator., (Copyright © 2014 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

The locus coeruleus (LC) is a chemoreceptive brain stem region in anuran amphibians and contains neurons sensitive to physiological changes in CO2/pH. The ventilatory and central sensitivity to CO2/pH is proportional to the temperature in amphibians, i.e., sensitivity increases with increasing temperature. We hypothesized that LC neurons from bullfrogs, Lithobates catesbeianus, would increase CO2/pH sensitivity with increasing temperature and decrease CO2/pH sensitivity with decreasing temperature. Further, we hypothesized that cooling would decrease, while warming would increase, normocapnic firing rates of LC neurons. To test these hypotheses, we used whole cell patch-clamp electrophysiology to measure firing rate, membrane potential (V(m)), and input resistance (R(in)) in LC neurons in brain stem slices from adult bullfrogs over a physiological range of temperatures during normocapnia and hypercapnia. We found that cooling reduced chemosensitive responses of LC neurons as temperature decreased until elimination of CO2/pH sensitivity at 10°C. Chemosensitive responses increased at elevated temperatures. Surprisingly, chemosensitive LC neurons increased normocapnic firing rate and underwent membrane depolarization when cooled and decreased normocapnic firing rate and underwent membrane hyperpolarization when warmed. These responses to temperature were not observed in nonchemosensitive LC neurons or neurons in a brain stem slice 500 μm rostral to the LC. Our results indicate that modulation of cellular chemosensitivity within the LC during temperature changes may influence temperature-dependent respiratory drive during acid-base disturbances in amphibians. Additionally, cold-activated/warm-inhibited LC neurons introduce paradoxical temperature sensitivity in respiratory control neurons of amphibians.

Background: Endoscopic submucosal dissection (ESD) has typically been performed using air insufflation. Recently, however, insufflation of CO2 has been increasingly used to avoid complications. This prospective study was designed to compare the CO2 concentration, intestinal volume, and acid-base balance using the duodenal balloon procedure., Methods: From June 2010 to February 2011, we enrolled 44 patients with esophageal or gastric cancer and randomly allocated them into two groups. We compared 22 patients undergoing CO2-insufflated ESD with a balloon placed into the duodenal bulb (duodenal balloon group) and 22 patients undergoing regular CO2-insufflated ESD (regular group). Three-dimensional computed tomography was performed before and after the procedure to measure intestinal volume. CO2 concentrations were measured every 10 minutes. The visual analogue system (VAS) scores for postoperative symptoms were recorded, and pH was measured immediately after the procedure. This was a prospective case control study randomized by the sealed envelope method., Results: Intestinal CO2 gas volume before and after ESD was lower in the duodenal balloon group than in the regular group (P = 0.00027). The end-tidal CO2 level was significantly lower in the duodenal balloon group than in the regular group (P = 0.0001). No significant differences in blood ΔpH were found between the two groups. The VAS score for the occurrence of nausea due to abdominal distension after ESD indicated a significant difference (P = 0.031)., Conclusions: ESD using the duodenal balloon occlusion method is effective for reduction of post-ESD intestinal CO2 gas volume, resulting in a lower total amount of CO2 insufflation during ESD and reducing harmful influences on the human body to some extent.

The carbon dioxide test--a vital capacity breath of air containing 35% carbon dioxide (CO(2))--provokes panic attacks in many individuals with panic disorder (PD). It has thus been extensively used as an experimental model of panic and less frequently as a clinical method of provoking symptoms for interoceptive exposure treatment. Recently, stress researchers have suggested another use for the CO(2) test: that of an acute physiological stressor indexing the human stress response. The purpose of this review is to synthesize findings about the effects of the CO(2) test from both the panic and stress literatures in order to advance understanding about this increasingly popular test. Both panic and stress researchers have examined the fleeting effects of the CO(2) test, finding that the test engenders transient breathlessness, dizziness, and minor anxiety in most participants and panic attacks in those with or at risk for PD. Physiological measurements after the test indicate a brief homeostatic disruption in many bodily systems, including increased respiration, systolic blood pressure, and noradrenaline, and decreased heart rate. Most studies indicate increased cortisol. Possible benefits of integrating findings from the panic and stress research lines, given their common use of the CO(2) test, are discussed., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

The purpose of this study was to test the hypothesis that sucralfate, a gastric ulcer medication, would alter plasma concentrations of total carbon dioxide (tCO2), lactate (LA), sodium (Na+), potassium (K+), chloride (Cl-) and total protein (TP), as well as calculated plasma strong ion difference (SID) and packed cell volume (PCV) in horses subjected to a simulated race test (SRT). Six unfit Standardbred mares (approximately 520 kg, 9-18 years) were used in a randomized crossover design with the investigators blinded to the treatment given. The horses were assigned to either a control (40-50 mL apple sauce administered orally (PO)) or a sucralfate (20 mg/kg bodyweight dissolved in 40-50 mL apple sauce administered PO) group. Each horse completed a series of SRTs during which blood samples were taken via jugular venipuncture at five sampling intervals (prior to receiving treatment, prior to SRT, immediately following exercise, and at 60 and 90 min post-SRT). During the SRTs, each horse ran on a treadmill fixed on a 6% grade for 2 min at a warm-up speed (4 m/s) and then for 2 min at a velocity predetermined to produce VO2max. Each horse then walked at 4 m/s for 2 min to complete the SRT. Plasma tCO2, electrolytes, LA, and blood PCV and TP were analysed at all intervals. No differences (P>0.05) were detected between control and sucralfate for any of the measured variables. There were differences (P<0.05) in tCO2, SID, PCV, TP, LA and electrolyte concentrations relative to sampling time. However, these differences were attributable to the physiological pressures associated with acute exercise and were not an effect of the medication. It was concluded that sucralfate did not alter plasma tCO2 concentration in this study., (Copyright (c) 2008 Elsevier Ltd. All rights reserved.)

This study investigated the effect of high CO2 (4%) from embryonic day (ED)10 until ED16 on the acid-base balance and related parameters in the chicken embryo. From ED10 to ED16, blood was taken from a vein from the chorioallantois membrane and was analyzed for pH, partial pressure of CO2, partial pressure of O2 (pO2), [HCO3(-)], [K+], and [Ca2+]. Allantoic fluid was taken for measurement of pH, NH3-N, phosphate, and calcium concentration. The right tibia was ashed, and calcium was measured with atomic absorption spectroscopy. Embryos exposed to high CO2 showed a consistent higher blood pH than control embryos. Notwithstanding this alkalosis, bicarbonate concentration was significantly higher in the CO2 group from ED12 until ED16. Potassium concentration in the blood was significantly higher in the CO2 group from ED11 until ED16. The pH of the allantois was significantly higher on ED14 and ED15. Ammonia N concentration was significantly higher in the CO2-incubated embryos on ED12 and ED13, whereas phosphate did not differ between groups. Calcium per tibia dry weight did not differ between incubation conditions. We can conclude that embryos adapt to high CO2 during the second half of incubation by increasing blood HCO3(-). It appears that this increase in HCO3(-)is mainly the result of the stimulated intracellular exchange of H+ with K+, although temporary reabsorption of HCO3(-)by the kidney cannot be excluded.

Recent studies show the importance of differential CO2 levels during the first half of incubation of chicken eggs on embryonic and postnatal growth. However, it is not known how external higher CO2 levels affect embryonic acid-base balance. In this study, the effect of an early rise in CO2, between 25th and 96th hour of incubation to 1.5% and maintained at that level until 240 h of incubation, was investigated on air cell gases, blood gas parameters from ED10 onwards and on embryonic growth and hatching parameters. Higher external CO2 concentrations resulted in a faster acidification of albumen resulting in a faster decrease of albumen pH with development, illustrating the capacity of albumen to cope with higher environmental CO2. Moreover, PCO2 in blood was higher in CO2 incubated embryos at embryonic day 10 and 11 but without a change in blood pH. The additional increase in plasma HCO3- concentration at day 10 and 11 was responsible for buffering the higher PCO2 in CO2 incubated embryos in order to stabilize pH. However, effects of hypercapnia on blood acid-base parameters extinguished 2 days after termination of high CO2 incubation. Embryonic growth was modestly accelerated which was reflected in higher embryonic weights at day 6 and 10 and a significant earlier hatching; hatchling weights were not different between treatment groups.

Plasma CO(2) reactions in Pacific spiny dogfish (Squalus acanthias) have access to plasma and gill membrane-associated carbonic anhydrase (CA). Acute severe experimental anemia and selective CA inhibitors were used to investigate the role of extracellular CA in CO(2) excretion. Anemia was induced by blood withdrawal coupled to volume replacement with saline. Lowering hematocrit from 14.2 +/- 0.4% (mean +/- SE; N = 31) to 5.2 +/- 0.1% (N = 31) had no significant impact on arterial or venous CO(2) tensions (Pa(CO(2)) and Pv(CO(2)), respectively) over the subsequent 2 h. PCO(2) was maintained despite the reduction in red cell number and a significant 32% increase in cardiac output (V(b)), both of which have been found to cause Pa(CO(2)) increases in teleost fish. By contrast, treatment of anemic dogfish with the CA inhibitors benzolamide (1.3 mg/kg) or F3500 (50 mg/kg), to selectively inhibit extracellular CA, elicited rapid and significant increases in Pa(CO(2)) of 0.68 +/- 0.17 Torr (N = 6) and 0.53 +/- 0.11 Torr (N = 7), respectively, by 30 min after treatment. These findings provide a functional context in which extracellular CA in dogfish contributes substantially to CO(2) excretion. Additionally, the apparent lack of effect of V(b) changes on PCO(2) suggests that, in contrast to teleost fish, CO(2) excretion in dogfish does not behave as a diffusion-limited system.

Small volume (0.5 ml) of arterial or venous rat's blood was subjected to impulse LPILR (lambda = 0.89 microns) in the light transparent cuvette. In arterial blood, a decrease of the pO2 (by 15.5 +/- 2.6%) and an increase of the pCO2 (by 22.0 +/- 4.8%) in respect to initial values, were determined. The acid-base shift from 7.39 +/- 0.02 to 7.34 +/- 0.02 was recorded. Only in few experiments, there were changes of pO2, pCO2 and pH in venous blood. Probable mechanism(s) of the mentioned parameters changes are discussed.

Increased CO(2) partial pressures (hypercapnia) as well as hypoxia are natural features of marine environments like the intertidal zone. Nevertheless little is known about the specific effects of CO(2) on metabolism, except for the well-described effects on acid-base variables and regulation. Accordingly, the sediment-dwelling worm Sipunculus nudus was used as an experimental model to investigate the correlation of acid-base-induced metabolic depression and protein/amino acid catabolism, by determining the rates of oxygen consumption, ammonia excretion and O/N ratios in non-perfused preparations of body wall musculature at various levels of extra- and intracellular pH, P(CO(2)) and [HCO(3)(-)]. A decrease in extracellular pH from control level (7.9) to 6.7 caused a reduction in aerobic metabolic rate of both normocapnic and hypercapnic tissues by 40-45 %. O/N ratios of 4.0-4.5 under control conditions indicate that amino acid catabolism meets the largest fraction of aerobic energy demand. A significant 10-15 % drop in ammonia excretion, a simultaneous reduction of O/N ratios and a transient accumulation of intracellular bicarbonate during transition to extreme acidosis suggest a reduction in net amino acid catabolism and a shift in the selection of amino acids used, favouring monoamino dicarboxylic acids and their amines (asparagine, glutamine, aspartic and glutamic acids). A drop in intracellular pH was identified as mediating this effect. In conclusion, the present data provide evidence for a regulatory role of intracellular pH in the selection of amino acids used by catabolism.

It is common practice to chronically implant catheters for subsequent blood sampling from conscious and undisturbed animals. This method reduces stress associated with blood sampling, but anaesthesia per se can also be a source of stress in animals. Therefore, it is imperative to evaluate the time required for physiological parameters (e.g. blood gases, acid-base status, plasma ions, heart rate and blood pressure) to stabilise following surgery. Here, we report physiological parameters during and after anaesthesia in the toad Bufo marinus. For anaesthesia, toads were immersed in benzocaine (1 g l(-1)) for 15 min or until the corneal reflex disappeared, and the femoral artery was cannulated. A 1-ml blood sample was taken immediately after surgery and subsequently after 2, 5, 24 and 48 h. Breathing ceased during anaesthesia, which resulted in arterial Po(2) values below 30 mmHg, and respiratory acidosis developed, with arterial Pco(2) levels reaching 19.5+/-2 mmHg and pH 7.64+/-0.04. The animals resumed pulmonary ventilation shortly after the operation, and oxygen levels increased to a constant level within 2 h. Acid--base status, however, did not stabilise until 24 h after anaesthesia. Haematocrit doubled immediately after cannulation (26+/-1%), but reached a constant level of 13% within 24 h. Blood pressure and heart rate were elevated for the first 5 h, but decreased after 24 h to a constant level of approximately 30 cm H2O and 35 beats min(-1), respectively. There were no changes following anaesthesia in mean cellular haemoglobin concentration, [K+], [Cl-], [Na+], [lactate] or osmolarity. Toads fully recovered from anaesthesia after 24 h.

Background: Because the data from previous experiments on the fetal effects of carbon dioxide (CO2) amniodistention in endoscopic fetal surgery are conflicting, we set out to evaluate the fetal acid-base status during CO2 amniodistention, with or without maternal hyperventilation, using a sheep model for endoscopic surgery., Methods: We assigned 26 pregnant ewes undergoing amniodistention with CO2 (4-5 mmHg intraamniotic pressure) to one of the following three groups: group I had fetal surgery + no maternal hyperventilation (n = 10); group II had fetal surgery + maternal hyperventilation (n = 10); group III had no fetal surgery + maternal hyperventilation (n = 6). Hyperventilation kept CO2 at 29-31 mmHg; in its absence, pCO2 ranged from 38 to 41. Fetal surgery consisted of fetoscopic tracheal clipping. Maternal blood pressure (mean, 98/69 mmHg) and heart rate (mean, 72 bpm) were kept at values comparable to human pregnancy. Fetal and maternal blood gas measurements were taken every 15 min during 1 h of amniodistention., Results: The ranges for baseline mean fetal pCO2 (mmHg) and pH were 51-55 and 7.24-7.25, respectively, in all study groups. After 1 h of amniodistention, mean +/- SEM values of fetal pCO2 and pH were 88 +/- 3 and 7.06 +/- 0.03 in group I, 69 +/- 4 and 7.13 +/- 0.02 in group II, and 71 +/- 5 and 7.14 +/- 0.04 in group III, respectively. Therefore, maternal hyperventilation attenuated but could not prevent significant fetal hypercarbia and acidosis. Fetal surgical manipulation had no effect on these observations., Conclusion: CO2 amniodistention should not be considered for clinical practice until ways of preventing its effects on the fetal acid-base status can be demonstrated.

Background: Bicarbonate therapy for metabolic acidosis can cause tissue hypercapnia. We tested the hypothesis that CO2 retention is initially confined to blood and that tissue hypercapnia is consequent to blood hypercapnia., Design: prospective study., Setting: general Intensive Care Unit in an University Hospital., Patients: ten patients, aged 34-84, undergoing fixed mechanical ventilation for stroke, respiratory failure, polytrauma, or coma and presenting fairly stabilized circulatory condition were included in the study providing that definite exclusion criteria were absent. Sodium bicarbonate, 0.08, 0.17, and 0.25 mEq/kg, was infused in 5 minutes during stages A, B, and C. During each stage, before and after bicarbonate infusion, heart rate, arterial pressure, central venous pressure, and PetCO2 were registered and arterial and central venous haemogasanalysis were performed. CO2 output was measured during and after bicarbonate infusion and total CO2 output over basal values was calculated., Results: Heart rate, arterial pressure, central venous pressure did not change in any stage, while PetCO2 increased in all. Following bicarbonate infusion, pH increased more in venous than in arterial blood and was significantly affected by the amount of bicarbonate infused. In arterial blood both PCO2 and total CO2 content (TCO2) increased. In venous blood PCO2 did not change while TCO2 increased so that arterial-venous rl CO2 difference was unaffected. CO2 output changed in no patient but two during stage A, and increased by 0.54 +/- 0.16 mL/kg during stage B and by 1.18 +/- 0.26 mL/kg during stage C so that 14.5 +/- 4.3 and 21.2 +/- 4.7% of given bicarbonate was released as CO2 through the lungs. CO2 output increased after a latency that was significantly shorter during stage C (145 +/- 51 sec) than during stage B (226 +/- 53 sec)., Conclusions: Since arterial-venous TCO2 difference was unaffected and haemodynamic parameters were stable, the conclusion is drawn that CO2 and bicarbonate did not diffuse out of vascular compartment during this study. However CO2 and bicarbonate diffusion out of blood would have occurred if bicarbonate infusion had continued, because CO2 excess was released through the lungs after a latency and extended after the infusion. Consequently, tissue hypercapnia during bicarbonate infusion could probably be prevented by improving CO2 release through the lungs, i.e. by hyperventilating the patient.

The influence of a CO2/HCO3(-)-buffered medium on intracellular pH regulation of gill pavement cells from freshwater rainbow trout was examined in monolayers grown in primary culture on glass coverslips; intracellular pH (pHi) was monitored by continuous spectrofluorometric recording from cells loaded with 2',7'-bis(2-carboxyethyl)-5(6)-carboxy-fluoroscein. When cells in HEPES-buffered medium at normal pH = 7.70 were transferred to normal CO2/HCO3(-)-buffered medium ¿PCO2 = 3.71 mmHg, [HCO3-] = 6.1 mmol l(-1), extracellular pH (pHe) = 7.70¿, they exhibited a brief acidosis but subsequently regulated the same pHi (approximately 7.41) as in HEPES. Buffer capacity (beta) increased by the expected amount (5.5-8.0 slykes) based on intracellular [HCO3-], and was unaffected by most drugs and treatments. However, after transfer to high PCO2 = 11.15 mmHg, [HCO3-] = 18.2 mmol l(-1) at the same pHe = 7.70, the final regulated pHi was elevated (approximately 7.53). The rate of correction of alkalosis caused by washout of this high PCO2, high-HCO3- medium was unaffected by removal of extracellular Cl-. Removal of extracellular Na + lowered resting pHi and greatly inhibited the rate of pHi recovery from acidosis. Bafilomycin A1 (3 micromol l(-1)) had no effect on these responses. However amiloride (0.2 mmol l(-1)) inhibited recovery from acidosis caused by washout of an ammonia prepulse, but did not affect resting pHi, the latter differing from the response in HEPES where amiloride also lowered resting pHi. Similarly 4-acetamido-4'- isothiocyanatostilbene-2,2'-disulfonic acid, sodium salt (0. 1 mmol l(-1)) did not affect resting pHi but slowed the rate of recovery from acidosis, though to a lesser extent than amiloride. Removal of extracellular Cl(-1) also slowed the rate of recovery but greatly increased beta by an unknown mechanism; when this was taken into account, H+ extrusion rate was unaffected. These results are consistent with the presence of Na+ -(HCO3)N co-transport and/or Na+-dependent HCO3(-)/Cl(-) exchange, in addition to Na+/H+ exchange, as mechanisms contributing to "housekeeping" pHi regulation in gill cells in CO2/HCO3(-) media, whereas only Na+/H+ exchange is seen in HEPES. Both Na(+)-independent Cl-/HCO3(-) exchange and V-type H(+)-ATPase mechanisms appear to be absent from these cells cultured in isotonic media.

It is commonly believed that during hyperbaric oxygen (HBO) treatment, in spite of the vasoconstriction induced by the increased O2 content in the breathing gas, the elevated carrying capacity of O2 in the arterial blood results in augmented O2 delivery to tissues. The experiments described here tested the hypothesis that HBO treatment would be more efficient in delivering O2 to poorly perfused tissues if the vasoconstriction induced by elevated O2 could be abolished or attenuated by adding CO2 to the breathing gas. Organ blood flow (QOBF), systemic hemodynamics, and arterial blood gases were measured before, during and after exposure to either 300 kPa O2 (group 1) or 300 kPa O2 with 2 kPa CO2 (group 2), in awake, instrumented rats. During the HBO exposure the respiratory frequency (fb) fell (4 breaths x min(-1) x 100 kPa O2(-1)), with no changes in arterial CO2 tension (PaCO2), but when CO2 was added, fb and PaCO2 increased. The left ventricular pressure (LVP) and the systolic arterial pressure (SBP) increased. The maximum velocity of LVP (+dP/dt) rose linearly with LVP whether CO2 was added or not (r2 = 0.72 and 0.75 respectively). Similarly, the cardiac output (Qc) and heart rate (fc) fell, while the stroke volume (SV) was unaltered, independent of PaCO2. There was a general vasoconstriction in most organs in both groups, with the exception of the central nervous system (CNS), eyes, and respiratory muscles. HBO reduced the blood flow to the CNS by 30%, but this vasoconstriction was diminished or eliminated when CO2 was added. In group 2, the blood flow to the CNS rose linearly with increased PaCO2 and decreased pH. After decompression fc and SBP stayed high, while Qc returned to control values by reducing the SV; CNS blood flow remained markedly elevated in group 2, while in group 1, it returned to control levels. We conclude that the changes in fc, Qc, LVP, dP/dt, SBP and most QOBF values induced by HBO were not changed by hypercapnia. Blood flow to the CNS decreased during HBO treatment at a constant PaCO2. Hypercapnia prevented this decline. Elevated PaCO2 augmented O2 delivery to the CNS and eyes, but increased the susceptibility to O2 poisoning. A prolonged suppression of O2 supply to the CNS occurred during the HBO exposure and in air following the decompression in the absence of CO2. This suppression was offset by the addition of CO2 to the breathing gas.

The effect of carbonic anhydrase inhibition with acetazolamide (Acz) on CO2 output (VCO2) and ventilation (VE) kinetics was examined during moderate- and heavy-intensity exercise. Seven men [24 +/- 1 (SE) yr] performed cycling exercise during control (Con) and Acz (10 mg/kg body wt iv) sessions. Each subject performed step transitions (6 min) in work rate from 0 to 100 W [below ventilatory threshold (VET)]. VE and gas exchange were measured breath by breath. The time constant (tau) was determined for exercise VET by using a three-component model (fit from the start of exercise). VCO2 kinetics were slower in Acz (VET, MRT = 75 +/- 10 s) than Con (VET, MRT = 54 +/- 7 s). During VET kinetics were faster in Acz (MRT = 85 +/- 17 s) than Con (MRT = 106 +/- 16 s). Carbonic anhydrase inhibition slowed VCO2 kinetics during both moderate- and heavy-intensity exercise, demonstrating impaired CO2 elimination in the nonsteady state of exercise. The slowed VE kinetics in Acz during exercise

Objective: To study the combined effects of intra-abdominal CO2 insufflation with changes in body position during laparoscopy in xylazine-ketamine-halothane anesthetized llamas., Study Design: Prospective, controlled study., Animals: Nine castrated, male llamas weighing 114 +/- 23 kg, 3 to 13 years old., Methods: Three llamas (preliminary study [PS] group) were used to study the effect of right, lateral, dorsal, and left lateral recumbency on gas exchange and acid-base status. The other six (experimental study [ES] group) were used to study the combined effects of changes in body position and CO2 insufflation to an intraabdominal pressure of 10 to 12 mm Hg. Heart rate, respiratory rate, and indirect arterial blood pressures (systolic [SAP], mean [MAP], and diastolic [DAP]) were recorded every 5 minutes during anesthesia. Arterial blood gases (PaO2 and PaCO2) and acid-base status (pHa and HCO3-) were measured immediately after induction of anesthesia and before each change of position., Results: In the PS group, significant decreases in SAP, MAP and PaCO2 and increases in PaO2 and pHa were observed when the llamas were turned from right lateral to dorsal recumbency. Values for HCO3- were lower than the postinduction values, but they remained unaffected by the changes in position. In the ES group, values for MAP were significantly lower when the llamas were placed in dorsal and left lateral recumbency than those observed during right lateral recumbency. Arterial O2 tension during right lateral recumbency was lower but returned to preinsufflation values when the llamas were placed in the dorsal position. All llamas recovered uneventfully within 30 minutes after termination of anesthesia., Conclusions: Insufflation of CO2 and changing body position induce minor and transient changes in cardiovascular and respiratory function., Clinical Relevance: Laparoscopy with mild intra-abdominal CO2 insufflation (10 to 12 mm Hg) can be used safely in spontaneously breathing llamas anesthetized with xylazine, ketamine, and halothane.

Abdominal CO2 insufflation has been shown to cause hypercarbia, acidemia, and decreased oxygenation in a pediatric animal model. Such metabolic derangements have prompted a search for alternative insufflation gases. This study compares the hemodynamic and ventilatory changes that occur during pneumoperitoneum with CO2 and helium. Four juvenile swine were intubated and given general anesthesia. Minute ventilation was adjusted to obtain a baseline Pco2 of between 32 and 36 mm Hg, and was kept constant for the duration of the experiment. The subjects initially were insufflated with CO2 or helium at a pressure of 10 mm Hg. Peak ventilatory pressure, end-tidal CO2 (ETCO2) arterial pH, Pco2, Po2, and right atrial and inferior vena caval pressures were measured before and during a 1-hour insufflation period. After desufflation, Pco2 and pH were restabilized. The same parameters were then measured during reinsufflation with the alternate gas. CO2 insufflation caused significant decreases in pH, from 7.51 +/- 0.03 to 7.32 +/- 0.06, and Po2 increased from 261 +/- 49 to 189 +/- 33 mm Hg. Pco2 increased from 35.0 +/- 1.4 to 57.9 +/- 6.3 mm Hg. ETCO2 also increased, from 29.0 +/- 2.2 to 47.2 +/- 5.0 mm Hg. Helium insufflation caused pH to decrease from 7.51 +/- 0.01 to 7.42 +/- 0.04. Pco2 increased from 32.8 +/- 0.8 to 43.5 +/- 3.9 mm Hg, and ETCO2 increased from 27.8 +/- 0.5 to 36.8 +/- 3.1 mm Hg. These alterations were significantly less than those with CO2 pneumoperitoneum. Po2 decreased as well-from 266 +/- 30 to 212 +/- 21 mm Hg. During insufflation with both gases, peak ventilatory pressure and right atrial pressure increased significantly. Abdominal insufflation with CO2 or helium causes hypercarbia, acidemia, and increased ETCO2 in this juvenile animal model. These derangements are significantly less with helium. This gas may prove to be the more suitable insufflation agent for pediatric patients.

To gain insight into the role of cerebral lactic acidosis in the hypoxic ventilatory response, we administered dichloroacetate (DCA) intravenously to inhibit lactic acid production in 7 awake goats (40-70 kg) during 0.5 h of normoxia (inspired O2 fraction = 0.209) and 5 h of poikilocapnic hypoxia (inspired O2 fraction = 0.125). On separate days, these goats were also studied with a continuous saline infusion (18 ml/h iv) during 5 h of normoxia and hypoxia. Arterial PCO2 (PaCO2) did not change during the 5-h normoxic period. During hypoxia, arterial PO2 fell significantly (P < 0.05) with both saline (from 111.3 to 39.0 Torr) and DCA (from 111.8 to 42.0 Torr) infusions. PaCO2 decreased (P < 0.05) during the first 0.5 h of both the saline and DCA hypoxia protocols. The decrease was greater (P < 0.05) during DCA (from 36.5 to 33.5 Torr) than during saline infusion (from 37.7 to 36.3 Torr). With saline infusion, PaCO2 decreased (P < 0.05) by 4.9 Torr between 0.5 and 5.0 h of hypoxia. However, over this period of DCA hypoxia, PaCO2 did not significantly decrease (P > 0.05). We conclude that the enhanced hyperventilation with DCA during acute hypoxia is consistent with brain lactic acidosis depressing breathing. Absence of additional significant hyperventilation after 0.5 h of DCA hypoxia suggests that a time-dependent alleviation of brain lactic acidosis might normally contribute to ventilatory acclimatization to hypoxia.

The hysteroscopic approach to the correction of congenital anomalies in utero may be helped by the temporary introduction of clear, electrically neutral fluids (liquids or gases) into the amniotic cavity. Accordingly, the authors determined the effects of three candidate fluids (helium, carbon dioxide, and water) on the oxygenation, acid-base balance, electrolyte concentrations, and hemodynamic function of nine sheep fetuses at 120 days' gestation (full term 145 days). Each fetus was exposed, in random order, to each of the three fluids, at an intraamniotic pressure of 15 mm Hg. The authors found that helium produced no changes in any of the measurements and was well tolerated by the fetus and the mother. Carbon dioxide decreased fetal arterial pH, and increased both arterial PCO2 and PO2. Although the decrease in pH was explained entirely by the increase in PCO2, the increase in arterial PO2 may have resulted from vasodilatation of the placental circulation or vasoconstriction of the fetal circulation with a redistribution of blood flow to the placenta. Water caused mild fetal hyponatremia and hypochloremia, without significant changes in acid-base balance or oxygenation. The results suggest that both helium and water may represent viable alternatives for amniotic fluid replacement during hysteroscopic surgery.

The effects of cavinton on serum erythropoietin levels, erythrocytic 2,3-DFG concentrations, acid-balance and lactic acid concentrations were studied in normal rats for 24 hours. The findings suggest that there might be two possible mechanisms of cavinton's action at the level of erythron: 1) impact on the determinants of hemoglobin functional properties; 2) creation of a potential for enhancing the production of erythropoietin.

The effects of progressive hypoxia, obtained by decreasing FIO2 from 0.21 to 0.12, on arterial blood gases and acid-base balance were studied in 13 awake rats and 13 rats anaesthetized with halothane (inspired concentration 1.1%). The effects on ventilation of the decrease in FIO2 from 0.21 to 0.12 were studied in eight rats, awake and then anaesthetized. Halothane causes a decrease in PaO2 and an increase in PaCO2; it abolishes the ventilatory response to hypoxia. The effects of hypoxia on PaCO2 were identical in awake and in anaesthetized rats. In the awake rats, PaO2 decreased from 90.3 +/- 5.9 mmHg to 42.3 +/- 3.6 mmHg, and PaCO2 decreased from 36.7 +/- 3.3 mmHg to 28.1 +/- 1.8 mmHg. In the anaesthetized rats, PaO2 decreased from 78.8 +/- 6.2 mmHg to 34.8 +/- 4.2 mmHg, and PaCO2 decreased from 40.7 +/- 2.8 mmHg to 31.9 +/- 3.7 mmHg. The decrease in PaCO2 during acute hypoxia in the anaesthetized rat could be explained by a decrease in CO2 production, secondary to a decrease in oxygen consumption due to the metabolic and circulatory effects of halothane and hypoxia.

We investigated the influence of CO2-induced acid-base changes on the potencies of the monoquaternary relaxants (rocuronium, vecuronium, and d-tubocurarine) and bisquaternary relaxants (pancuronium, pipecuronium, and metocurine), and on the antagonism of their neuromuscular block by neostigmine. Phrenic nerve-hemidiaphragm preparations of rats were used. The pH changes were induced by changing the CO2 concentration aerating the modified Krebs solution. The potencies of the monoquaternary relaxants increased at 9% CO2 (pH 7.2) and decreased at 2.5% CO2 (pH 7.6) from those of 5% CO2 (pH 7.4) both with and without neostigmine (P < 0.05), whereas the potencies of the bisquaternary drugs did not change significantly at different pH levels from control (pH 7.4) both with and without neostigmine. The slopes of the log concentration-percent response curves of each drug were not significantly different at each pH level. The ratios of inhibitory concentrations, 50% (IC50) values with and without neostigmine at each pH value for each drug were not significantly different indicating that the neostigmine-induced antagonism for each drug was not affected by the CO2-induced acid-base changes. But the ratios of the IC50 values of the steroidal relaxants (rocuronium, vecuronium, pancuronium, and pipecuronium) were significantly lower (P < 0.05) than those of the isoquinolinium drugs (d-tubocurarine and metocurine) at each pH level, suggesting that the antagonism is enhanced at each pH level for the isoquinolinium relaxants. The difference was independent of their monoquaternary or bisquaternary nature. These results suggest that CO2 increases the potency of the monoquaternary relaxants but does not affect the bisquaternary relaxants.(ABSTRACT TRUNCATED AT 250 WORDS)

Halothane decreases the ventilatory response to hypoxia and the activity of peripheral arterial chemoreceptors, resulting in "chemical chemodenervation." In order to evaluate the role of this halothane-induced "chemical denervation" in acid-base and arterial blood gas changes, these values were measured in intact and chemodenervated rats, awake and under anaesthesia. Since the depth of anaesthesia could be modified by the anatomical chemodenervation, the ED50 of inspired halothane was determined in six rats before and after anatomical chemodenervation. To prevent haemodynamic changes due to halothane and/or anatomical chemodenervation from interfering with the results, systemic arterial blood pressure and heart rate were measured in six intact rats, awake and then anaesthetized, and in the same rats after chemodenervation, awake and then anaesthetized. In nine intact rats and in 19 chemodenervated rats, arterial pH, arterial bicarbonate concentration, and arterial blood gases (PaO2 and PaCO2) were measured before and after administration of halothane. Anatomical chemodenervation modified neither the inspired ED50 (1.1%), nor the mean arterial blood pressure or heart rate. The haemodynamic effects of halothane were comparable in intact and in chemodenervated rats. Changes in arterial blood gases and acid-base balance due to halothane in intact rats and due to chemodenervation in awake rats were not different, but there was a decrease in PaO2 and pHa, and an increase in PaCO2. In chemodenervated rats, halothane caused a further decrease in PaO2 and a further increase in PaCO2. The fact that halothane and anatomical chemodenervation have similar effects on arterial blood gases and acid-base balance favours a "chemical chemodenervating" action of halothane. However, the additional effects of halothane in the anatomically chemodenervated animal show that the action of halothane on blood gases and acid-base balance is the result of multiple sites of impact on the respiratory system.

Experiments were conducted to test the hypothesis that one or more interrenal steroids are active in regulatory responses to respiratory acidosis in the toad, Bufo marinus. Toads were divided into four experimental groups. The first group received sham injections. The second group received 1-3 mg of aminoglutethimide (AG) every 8 hr. AG inhibits the conversion of cholesterol to pregnenolone, thus inhibiting all steroid hormone synthesis. The third group received AG + 5 micrograms of aldosterone on the same schedule. The fourth group received AG + 25 micrograms of corticosterone on the same schedule as the other groups. All four groups were subjected to hypercapnia using 5% CO2 to induce a respiratory acidosis. The sham-operated animals displayed the normal compensatory pattern of producing a metabolic alkalosis (elevated plasma HCO3-) after 24 hr. AG-treated toads failed to elevate plasma HCO3-. Administration of interrenal steroids produced compensation in varying degrees. Aldosterone produced a small compensation while corticosterone produced a compensation similar to that seen in sham-operated animals. Analysis of steroid titers in toad plasma during hypercapnia showed that Bufo marinus does not elevate aldosterone during respiratory acidosis, but that corticosterone is elevated. AG blocked the corticosterone elevation, however. AG also produced a hyponatremia that was corrected with aldosterone or corticosterone. Normocapnic controls showed that AG does not produce deleterious effects on pH or blood gases in toads in the absence of a respiratory acidosis. We conclude that corticosterone is important in acid-base regulatory responses to respiratory acidosis in this amphibian.

Blood oxygen transport, pH, acid-base status, urinary ketone level and urobilinogen were studied in 52 pregnant women in whom pregnancy ran a normal course and in 56 ones with a history of habitual abortions, treated for metabolic disorders. Signs of metabolic acidosis in the presence of respiratory alkalosis at the expense of pulmonary hyperventilation were detected in women with normal pregnancy. Follow-up of acid-base status and gases of blood, aciduria and ketonuria in pregnant women with a history of habitual abortions has revealed in them respiratory alkalosis signs presenting in hypoxemia and reduced oxygen saturation and ketonuria. Metabolic therapy included in combined therapeutic schemes for such patients actively influenced the processes of metabolic acidosis and ketonuria compensation, probably at the expense of its normalizing effect on intracellular metabolism. Metabolic therapy of pregnant women liable to spontaneous abortions, due to ovarian hypofunction had a marked antihypoxic effect, normalized the bicarbonate system status and was therefore conducive to improvement of oxygen transport to maternal tissues and the fetus.

Variations of the phosphate concentration in plasma were studied in two groups of 12 patients undergoing cardiac surgery with hypothermic cardiopulmonary bypass (CPB). Management of the acid-base status differed between the groups, according to whether or not carbon dioxide was added to the anesthetic gas mixture during hypothermia ('pH-stat' vs. 'alpha-stat' mode) following correction vs. no correction of pCO2 and pH for body temperature. Phosphate variations throughout the study were mostly within normal limits. From the start to the end of CPB, the mean rise in phosphate levels was 70% in the pH-stat group and 37% in the alpha-stat group (p < 0.001). During 3 hours after CPB, the phosphate values continued to rise by a mean of 25% in the alpha-stat patients, but fell by a mean of 3% in the pH-stat patients (p < 0.001). Such different phosphate patterns during and immediately after CPB may reflect profound metabolic disturbances and may be related to the altering effects of CO2 addition and respiratory acidosis on intracellular metabolic activity and phosphate homeostasis.

The purpose of this study was to investigate the effects of bumetanide, an inhibitor of NaCl cotransport on cisternal cerebral spinal fluid (CSF) acid-base balance during acute respiratory acidosis (ARA). We measured blood and CSF acid-base variables in two groups (N = 7 in each) of anesthetized paralyzed and mechanically ventilated dogs with bilateral ligation of renal pedicles (to eliminate saluresis). After baseline samples were obtained (-1 h) bumetanide (0.5 mg/kg) was administered intravenously within 15 min (group 2); group 1 received equal volume of diluted saline. ARA was induced 1 h later (0 h) and was maintained for 5 h. In both groups PaCO2 was maintained between 55 to 60 mm Hg. Mean cisternal CSF PCO2 was 42.8 +/- 2.6, and 43.8 +/- 2.5 mm Hg, respectively in group 1 and group 2 and rose approximately 20 mm Hg during ARA. In group 1, CSF [HCO3-] was 22.0 +/- 1.0, 24.8 +/- 0.6, and 25.4 +/- 1.6 mEq/L, respectively at 0, 2 1/2, and 5 h; respective values for group 2 were 22.9 +/- 1.5, 24.7 +/- 1.4, and 26.1 +/- 1.3 mEq/L. Comparing the two groups, respective values were not significantly different from each other. Similarly, between the two groups changes in CSF [Na(+)-Cl-] during ARA were not significantly different from each other. Based on our results we conclude that at the dose used in the present study bumetanide does not change ionic composition and acid-base balance of cisternal CSF when compared to controls. Because changes in CSF [Na(+)-Cl-] during ARA were similar in both groups, any inhibition of Cl- influx into CSF by bumetanide should have been proportional to that of Na+.

Cutaneous CO2 excretion is reduced as the skin dries during dehydration but an increase in breath frequency acts to regulate the arterial blood PCO2 and thus pHa. Moreover, the toad does not urinate and water is reabsorbed from the bladder to replace that lost by evaporation at the skin and lung surfaces. The animal does, however, produce a very acid bladder urine to conserve circulating levels of plasma [HCO3-] and this together with an increased ventilation effectively maintains the blood acid-base status for up to 48 h of dehydration in air. Water loss and acid production are presumably also reduced by the animal's behaviour; animals remain still, in a crouched position or in a pile if left in groups. Dehydrated toads are less able than hydrated toads to regulate blood pH during hypercapnia: they hyperventilate and mobilize body bicarbonate stores in much the same fashion as hydrated animals but due to the restrictions on cutaneous CO2 excretion and renal output, there is comparatively little reduction in the PCO2 difference between arterial blood and inspired gas thereby resulting in a more severe respiratory acidosis. These factors further contribute to the persistent acidosis which continues even when the animals are returned to air.

We examined both the role of HCO3-CO2 in Cl transport as well as the effect of in vivo acid-base status on Cl transport by the rabbit cortical collecting tubule. The lumen-to-bath 36Cl tracer flux, expressed as the rate coefficient KCl, was measured in either HEPES-buffered (CO2-free) or HCO3-CO2-containing solutions. Amiloride was added to the perfusate to minimize the transepithelial voltage and thus the electrical driving force for Cl diffusion. Because KCl fell spontaneously with time in HCO3-CO2 solutions in the absence but not the presence of cAMP, we used cAMP throughout to avoid time-dependent changes. Acute in vitro removal of bath HCO3-CO2 reduced KCl. Acetazolamide addition in HEPES-buffered solutions also lowered KCl; KCl could be restored to control values by adding exogenous HCO3-CO2 in the presence of acetazolamide. In vivo acid-base effects on Cl transport were determined by dissecting tubules from either NaHCO3-loaded or NH4Cl-loaded rabbits. Tubules from HCO3-loaded rabbits had higher rates of Cl self exchange. Acute in vitro addition of bath HCO3-CO2 increased KCl and did so to a greater degree in tubules from HCO3-loaded rabbits. Most of this effect of HCO3-CO2 addition on KCl could not be accounted for by Cl-HCO3 exchange; rather, it appeared due to stimulation of Cl self exchange. The data are consistent with 36Cl transport occurring via Cl-HCO3 exchange as well as Cl self exchange. Both processes are acutely stimulated by HCO3 and/or Co2, and both are chronically regulated by in vivo acid-base status.

Concentration-dependent effects of ethanol upon behavior and upon physiological regulatory mechanisms have been suggested. In a previous study, we found that the concentration of an acute ethanol injection confounded dose-response relationships for measures of blood pH, PCO2, and PO2. Two lines of mice that differ in CNS sensitivity to the hypnotic effects of ethanol (long sleep, LS; short sleep, SS) have also been found to differ in sensitivity to the physiological depressant effects of this drug. Therefore, we designed the present study to examine how intraperitoneal (IP) injections of varying ethanol concentrations differentially affect blood parameters (pH, PCO2, and PO2) and respiration rate in the LS and SS mouse lines. Different groups of LS female mice were injected IP with 165.0, 198.8, 248.1, or 330.0 mg/ml ethanol at a constant dose of 3.3 g/kg. Groups of SS female mice received 205.0, 247.0, 308.3, or 410.0 mg/ml ethanol at a dose of 4.1 g/kg. Blood parameters and respiration rate were measured at 60 min post-injection. In both the LS and SS mice, increasing concentrations of ethanol caused a progressive decline in respiration rate and blood pH. Blood PCO2 values were greater than control only at the highest ethanol concentration. Concentration-dependent effects of ethanol on blood PO2 values were not found in either line. However, LS PO2 was significantly elevated from the control value at all ethanol concentrations. These results suggest that a dose-response relationship may be obtained by varying ethanol concentration for some physiological measures, but not for others. Thus, attention should be paid to differences in concentration as well as amount of ethanol when dose-response curves are to be constructed.

The aim of this work was to study the cardiovascular effects, the acid-base balance in serum electrolytes and chlorides in 50 patients during diagnostic laparoscopy, comparing the use of CO2 and N2O for pneumoperitoneum. The CO2 group showed a significant decrease in pH, a significant increase in pCO2 and a significant decrease in pO2, while the changes in HCO3 and base change were insignificant. In the N2O group, the changes in pH, pCO2, pO2, HCO 3 and base excess were statistically insignificant. The heart rate during CO2 and N2O pneumoperitoneum revealed that both groups showed a significant increase, but in the recovery stage there was a significant increase in the CO2 group (p less than 0.025) and insignificant increase in the N2O group (p greater than 0.05). The other circulatory and electrocardiographic changes are described. CO2 pneumoperitoneum induced a significant decrease in serum chlorides but an insignificant increase in Na and an insignificant decrease in potassium, while the N2O pneumoperitoneum group did not show any significant change in serum electrolytes.

The effects of ethanol on blood pH, PCO2, and PO2 were measured in LS and SS mice in an attempt to ascertain whether these lines of mice, which differ in CNS sensitivity to the behavioral effects of ethanol, also differ in sensitivity to physiological effects of this drug. Long-sleep (LS) female mice were injected intraperitoneally with 1.8, 2.5, 3.3, or 3.8 g/kg ethanol; short-sleep (SS) female mice were administered 2.5, 3.3, 4.1, or 4.7 g/kg. Blood pH, PCO2, and PO2 were assessed at 15, 30, 60, 120, or 180 min after injection of the 2.5 and 4.1 g/kg doses or at 60 min after injection of the 1.8, 2.5, 3.3, 3.8, 4.1, and 4.7 g/kg doses. Opposite effects on blood pH and PCO2 over time were obtained in LS and SS mice at the 2.5 g/kg dose. Acidosis characterized the LS line, whereas alkalosis characterized the SS. The results obtained with SS mice at 4.1 g/kg dose were similar to those obtained with LS mice at the 2.5 g/kg dose. The dose-response curve for the SS mice generated at 60 min post-injection lies to the right of that for the LS mice. The effects of high ethanol doses on SS mice resemble the effects of low doses on LS animals. Thus, the two lines of mice differ in response to the effects of ethanol on these parameters related to respiration. The difference in sensitivity to the respiratory depressant effects of ethanol may contribute to the differences in behavioral sensitivity between the two lines.

End-tidal PCO2 and base excess were measured on 10 healthy females throughout a total of 16 menstrual cycles. A corresponding decrease was observed in both variables during the luteal phase of the cycle. The curve for PCO2 was essentially that reported by previous authors, the tension dropping from a mean value of 39.8 to 36.7, 10 days after ovulation. The parallel drop in BE lowered the variable from -0.5 to -2.6. The resulting arterial pH throughout the cycle was calculated to be between 7.38 and 7.40. Since no time lag could be observed between the change in PCO2 and that of base excess, the primary disturbance could be either a ventilatory or metabolic response to an increase in progesterone during the luteal phase. In either case, a considerable decrease in body CO2 stores must result from these changes.

In the control trials on near-term pregnant women before the onset of labour, nalorphine was found to cause a mild respiratory acidosis in the mother and metabolic acidosis in the fetus. These effects were not apparent when naloxone was administered.