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This article reports on respiratory function in white rhinoceros (Ceratotherium simum) immobilized with etorphine-azaperone and the changes induced by butorphanol administration as part of a multifaceted crossover study that also investigated the effects of etorphine or etorphine-butorphanol treatments. Six male white rhinoceros underwent two immobilizations by using 1) etorphine-azaperone and 2) etorphine-azaperone-butorphanol. Starting 10 min after recumbency, arterial blood gases, limb muscle tremors, expired minute ventilation, and respiratory rate were evaluated at 5-min intervals for 25 min. Alveolar to arterial oxygen gradient, expected respiratory minute volume, oxygen consumption, and carbon dioxide production were calculated. Etorphine-azaperone administration resulted in hypoxemia and hypercapnia, with increases in alveolar to arterial oxygen gradient, oxygen consumption, and carbon dioxide production, and a decrease in expired minute ventilation. Muscle tremors were also observed. Intravenous butorphanol administration in etorphine-azaperone-immobilized white rhinoceros resulted in less hypoxemia and hypercapnia; a decrease in oxygen consumption, carbon dioxide production, and expired minute ventilation; and no change in the alveolar to arterial oxygen gradient and rate of breathing. We show that the immobilization of white rhinoceros with etorphine-azaperone results in hypoxemia and hypercapnia and that the subsequent intravenous administration of butorphanol improves both arterial blood oxygen and carbon dioxide partial pressures., (© Wildlife Disease Association 2024.)

Objective: To investigate the effect of hypoxaemia, hypotension and hypercapnia, among others, on quality of recovery from general anaesthesia in horses., Study Design: Retrospective, single-centre study., Animals: A sample of 1226 horses that underwent general anaesthesia between June 2017 and June 2021., Methods: Horses and ponies weighing > 200 kg, aged > 6 months, anaesthetized using a xylazine- or medetomidine-isoflurane balanced anaesthesia protocol and presenting a complete anaesthetic record were included. Data were extracted from the clinic record system and from the original anaesthesia records. Recoveries were divided into 'good' and 'bad' based on the available recovery scores. Influence of hypoxaemia [PaO 2 < 60 mmHg (7.99 kPa)], hypotension (mean arterial pressure < 70 mmHg for at least 15 minutes) and hypercapnia [PaCO 2 > 60 mmHg (7.99 kPa)], anaesthesia protocol, body weight, age, breed, sex, American Society of Anesthesiologists status, type of procedure, emergency or nonemergency, duration of anaesthesia, positioning, times spent in lateral and sternal recumbency during recovery, time until standing and nonassisted or assisted recovery on the assigned recovery score (good/bad) were investigated using generalized linear regression analysis (p < 0.05)., Results: Hypoxaemia and prolonged duration of anaesthesia were significantly associated with a bad recovery score. No other factors had a significant influence on recovery quality., Conclusion and Clinical Relevance: Hypoxaemia and prolonged anaesthesia duration have a negative effect on quality of anaesthetic recovery in horses. Clinically, this highlights the importance of keeping anaesthetic time as short as possible and to monitor oxygenation and treat hypoxaemia as soon as possible., (Copyright © 2023 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.)

Objectives: This study compared the effectiveness of a new supraglottic airway device (SGAD) in cats undergoing anaesthesia using two types of mechanical ventilation: volume-controlled ventilation (VCV) and pressure-controlled ventilation (PCV)., Methods: A total of 13 healthy cats (five male, eight female; median age 2 years [range 1-3]) were randomly allocated to either VCV or PCV. Five tidal volumes (6, 8, 10, 12 and 14 ml/kg) and five peak inspiratory pressures (4, 5, 6, 7 and 8 cmH 2 O) were randomly applied with a minute ventilation of 100 ml/kg/min. Various parameters, such as blood pressure, gas leakage, end-tidal CO 2 (ETCO 2 ) and work of breathing (WOB), were measured while using VCV or PCV., Results: The occurrence of hypotension (mean arterial blood pressure <60 mmHg) was slightly less frequent with VCV (38 events, 65 ventilating sessions) than with PCV (40 events, 65 ventilating sessions), but this difference did not reach statistical significance ( P  = 0.429). The number of leakages did not differ between the VCV group (3 events, 65 ventilating sessions) and the PCV group (3 events, 65 ventilating sessions) ( P  = 1.000). Hypercapnia was identified when using VCV (10 events, 65 ventilating sessions) less frequently than when using PCV (17 events, 65 ventilating sessions), but this difference did not reach statistical significance ( P  = 0.194). The study found a significantly higher WOB in the PCV group compared with the VCV group ( P <0.034)., Conclusions and Relevance: The present results suggested that both VCV and PCV can be used with an SGAD during anaesthesia, with VCV preferred for prolonged mechanical ventilation due to its lower workload. Adjusting tidal volume or inspiratory pressure corrects hypercapnia., Competing Interests: Conflict of interestThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Continuous positive airway pressure (CPAP) and pressure support ventilation (PSV) can improve respiratory mechanics and gas exchange, but different airway pressures have not been compared in foals., Hypothesis/objectives: Assess the effect of different airway pressures during CPAP and PSV have on respiratory function in healthy foals with pharmacologically induced respiratory insufficiency. We hypothesized that increased airway pressures would improve respiratory mechanics and increased positive end-expiratory pressure (PEEP) would be associated with hypercapnia., Animals: Six healthy foals from a university teaching herd., Methods: A prospective, 2-phase, 2-treatment, randomized cross-over study design was used to evaluate sequential interventions in sedated foals using 2 protocols (CPAP and PSV). Outcome measures included arterial blood gases, spirometry, volumetric capnography, lung volume and aeration assessed using computed tomography (CT)., Results: Sedation and dorsal recumbency were associated with significant reductions in arterial oxygen pressure (PaO 2 ), respiratory rate, and tidal volume. Continuous positive airway pressure was associated with improved PaO 2 , without concurrent hypercapnia. Volumetric capnography identified improved ventilation:perfusion (V/Q) matching and increased carbon dioxide elimination during ventilation, and spirometry identified decreased respiratory rate and increased tidal volume. Peak inspiratory pressure was moderately associated with PaO 2 and lung volume. Improved pulmonary aeration was evident in CT images, and lung volume was increased, particularly during CPAP., Conclusions and Clinical Importance: Both CPAP and PSV improved lung mechanics and gas exchange in healthy foals with induced respiratory insufficiency., (© 2023 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC. on behalf of the American College of Veterinary Internal Medicine.)

Objective: To compare cardiopulmonary variables and blood gas analytes in guinea pigs (Cavia porcellus) during anesthesia with and without abdominal carbon dioxide (CO 2 ) insufflation at intra-abdominal pressures (IAPs) 4 and 6 mmHg, with and without endotracheal intubation., Study Design: Prospective experimental trial., Animals: A total of six intact female Hartley guinea pigs., Methods: A crossover study with sequence randomization for IAP and intubation status was used. The animals were sedated with intramuscular midazolam (1.5 mg kg -1 ) and buprenorphine (0.2 mg kg -1 ) and anesthetized with isoflurane, and an abdominal catheter was inserted for CO 2 insufflation. Animals with endotracheal intubation were mechanically ventilated and animals maintained using a facemask breathed spontaneously. After 15 minutes of insufflation, the following variables were obtained at each IAP: pulse rate, respiratory rate, rectal temperature, oxygen saturation, end-tidal CO 2 (intubated only), peak inspiratory pressure (intubated only), noninvasive blood pressure and blood gas and electrolyte values, with a rest period of 5 minutes between consecutive IAPs. After 4 weeks, the procedure was repeated with the guinea pigs assigned the opposite intubation status., Results: Intubated guinea pigs had significantly higher pH and lower partial pressure of CO 2 in cranial vena cava blood (PvCO 2 ) than nonintubated guinea pigs. An IAP of 6 mmHg resulted in a significantly higher PvCO 2 (65.9 ± 19.0 mmHg; 8.8 ± 2.5 kPa) than at 0 (53.2 ± 17.2 mmHg; 7.1 ± 2.3 kPa) and 4 mmHg (52.6 ± 10.8 mmHg; 7.01 ± 1.4 kPa), mean ± standard deviation, with intubated and nonintubated animals combined., Conclusions and Clinical Relevance: Although the oral anatomy of guinea pigs makes endotracheal intubation difficult, capnoperitoneum during anesthesia induces marked hypercapnia in the absence of mechanical ventilation. An IAP of 4 mmHg should be further evaluated for laparoscopic procedures in guinea pigs because hypercapnia may be less severe than with 6 mmHg., (Copyright © 2022 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.)

Objective: Acidosis decreases myocardial contractile and myofibrillar responsiveness by reducing the calcium sensitivity of contractile proteins, which could reduce the effectiveness of pimobendan. We aimed to assess the cardiovascular effects of pimobendan in dogs subjected to acute respiratory acidosis., Design: Randomized crossover study with a 2-week washout period., Setting: University Laboratory., Animals: Six healthy research Beagle dogs., Interventions: Anesthetized dogs were administered 2 doses of IV pimobendan during conditions of eucapnia (Paco 2 35-40 mm Hg) and hypercapnia (Paco 2 90-110 mm Hg). Eucapnia was maintained by positive pressure ventilation and hypercapnia was induced by adding exogenous CO 2 to the anesthesia circuit. Heart rate (HR), systemic arterial blood pressure, cardiac output (CO), systemic and pulmonary vascular resistance (SVR and PVR, respectively), and pulmonary arterial pressure (PAP) were measured at baseline and 60 min after administering 0.125 mg/kg (low) and 0.25 mg/kg (high) pimobendan intravenously. Blood gas and biochemical analyses were performed at baseline and at the end of the experiment., Measurements and Main Results: The median baseline blood pH was 7.41 (range: 7.33-7.45) and 7.03 (range: 6.98-7.09) under conditions of eucapnia and hypercapnia, respectively. The serum concentrations of epinephrine and norepinephrine and the HR, CO, and PAP were higher, and SVR was lower at baseline in hypercapnic dogs. Pimobendan dose-dependently increased CO in eucapnia (baseline: 3.6 ± 0.2 L/kg/m 2 [mean ± SE], low: 5.0 ± 0.4 L/kg/m 2 , high: 5.8 ± 0.5 L/kg/m 2 , P < 0.001) and hypercapnia (baseline: 4.9 ± 0.5 L/kg/m 2 , low: 5.8 ± 0.5 L/kg/m 2 , high: 6.2 ± 0.5 L/kg/m 2 , P < 0.001), and increased HR and decreased SVR and PVR under both conditions (P < 0.001). In hypercapnia, the degree of increase or decrease of these cardiovascular measurements (except for PAP) by pimobendan was less than that in the eucapnic dogs., Conclusions: Pimobendan maintains function as an inodilator in anesthetized dogs with induced respiratory acidosis., (© Veterinary Emergency and Critical Care Society 2022.)

Aims: To evaluate associations between clinicopathological variables and hypercapnia measured in cats with decompensated chronic kidney disease (CKD) on admission to a veterinary hospital., Methods: This is a retrospective, cross-sectional study of cats (n = 39) that presented to a tertiary veterinary hospital in Argentina between June 2015 and December 2017 with blood creatinine concentrations >140 μmol/L, and abdominal ultrasound results consistent with CKD. Data recorded included venous partial pressure of CO 2 (PvCO 2 ), blood pH, haematocrit and concentrations of glucose, potassium, sodium, corrected sodium (Na + c ), and ionised calcium in blood. A logistic regression model was used to assess associations between the presence of hypercapnia (PvCO 2  ≥ 44.7 mmHg) and the other clinicopathologic variables. The duration of hospitalisation was compared in cats with and without hypercapnia using the Wilcoxon Rank Sum test., Results: The final study population comprised 39 cats. Eleven cats (28.2%) had hypercapnia. In the logistic regression model, two independent variables were associated with the presence of hypercapnia at admission in cats with CKD: the concentration of creatinine in blood (OR = 1.06 (95% CI = 1.016-1.108); p = 0.007) and Na + c (OR = 1.33 (95% CI = 1.08-1.63); p = 0.005). There were no statistically significant differences in the length of hospital stay between the two groups., Conclusions and Clinical Relevance: There appears to be an association between elevated concentrations of creatinine and Na + c in blood, and hypercapnia in cats with CKD, suggesting careful assessment of blood gas and electrolyte parameters during hospitalisation is required. Further prospective studies are needed to evaluate the mechanisms behind this association and the association of hypercapnia with disease outcome including mortality.

Cardiac arrhythmias are common in horses during exercise, especially immediately post-exercise. The objectives of this study were to: (1) describe the frequency and type of cardiac arrhythmias detected in horses during incremental high-speed treadmill exercise testing (ITET); (2) determine if arterial blood gas (ABG) changes at peak and immediately post-exercise were associated with arrhythmias; and (3) determine whether upper or lower airway disease was associated with exercising cardiac arrhythmias. Horses (n = 368) presenting for an ITET underwent resting and exercising upper airway endoscopy, resting, exercising and post-exercise electrocardiography, resting and post-exercise echocardiography and exercising ABG. Arrhythmias were graded by the most severe arrhythmia present. Grade 1 arrhythmias were defined as one or two atrial (APCs) or ventricular premature complexes (VPCs), or one APC and one VPC, detected in 6.9% at peak and 16% at 0-2 min post exercise.. Grade 2 arrhythmias were >2 APCs or VPCs, or both, detected in 5.8% at peak and 16.6% at 0-2 min post exercise. Grade 3 included complex arrhythmias (couplets, triplets, R on T, multiform complexes or paroxysmal atrial or ventricular tachycardia), detected in 4.4% at peak and 7.3% at 0-2 min post exercise. Both partial pressure of arterial CO 2 (PaCO 2 ; P = 0.008) and lactate (P = 0.031) were significantly associated with arrhythmias occurring at peak exercise, but not immediately post-exercise. As PaCO 2 and lactate increased, arrhythmia severity increased. Blood pH was significantly associated with grades 2 and 3 arrhythmias at 0-2 min post ITET (OR = 0.0002; P < 0.001). There was no significant association between grades 2 and 3 cardiac arrhythmias, inflammatory airway disease (IAD), or exercise-induced pulmonary hemorrhage (EIPH). When adjusted for lactate concentration (P = 0.06), higher PaCO 2 concentrations in horses with and without exercising upper respiratory tract (URT) obstruction were associated with higher likelihood of grades 2 and 3 arrhythmias (P < 0.01). This study demonstrated that at peak exercise, with severe hypercapnia and hyperlactatemia, there was increased risk for grades 2 or 3 cardiac arrhythmias and, as the PaCO 2 and lactate values increased further, the severity of those arrhythmias increased., (Copyright © 2020. Published by Elsevier Ltd.)

The aim of this study was to corroborate the presence of CO 2 /H + -sensitive arterial chemoreceptors involved in producing air-breathing responses to aquatic hypercarbia in the facultative air-breathing clown knifefish (Chitala ornata) and to explore their possible location. Progressively increasing levels of CO 2 mixed with air were injected into the air-breathing organ (ABO) of one group of intact fish to elevate internal PCO 2 and decrease blood pH. Another group of fish in which the gills were totally denervated was exposed to aquatic hypercarbia (pH ~ 6) or arterial hypercapnia in aquatic normocarbia (by injection of acetazolamide to increase arterial PCO 2 and decrease blood pH). Air-breathing frequency, gill ventilation frequency, heart rate and arterial PCO 2 and pH were recorded during all treatments. The CO 2 injections into the ABO induced progressive increases in air-breathing frequency, but did not alter gill ventilation or heart rate. Exposure to both hypercarbia and acetazolamide post-denervation of the gills also produced significant air-breathing responses, but no changes in gill ventilation. While all treatments produced increases in arterial PCO 2 and decreases in blood pH, the modest changes in arterial PCO 2 /pH in the acetazolamide treatment produced the greatest increases in air-breathing frequency. These results strengthen the evidence that internal CO 2 /H + sensing is involved in the stimulation of air breathing in clown knifefish and suggest that it involves extra-branchial chemoreceptors possibly situated either centrally or in the air-breathing organ.

Despite the prevalence of CO 2 retention in human disease, little is known about the adaptive neurobiological effects of chronic hypercapnia. We have recently shown 30-d exposure to increased inspired CO 2 (InCO 2 ) leads to a steady-state ventilation that exceeds the level predicted by the sustained acidosis and the acute CO 2 /H + chemoreflex, suggesting plasticity within respiratory control centers. Based on data showing brainstem changes in aminergic and inflammatory signaling during carotid body denervation-induced hypercapnia, we hypothesized chronic hypercapnia per se will lead to similar changes. We found that: 1 ) increased InCO 2 increased IL-1β in the medullary raphe (MR), ventral respiratory column, and cuneate nucleus after 24 h, but not after 30 d of hypercapnia; 2 ) the number of serotonergic and total neurons were reduced within the MR and ventrolateral medulla following 30 d of increased InCO 2 ; 3 ) markers of tryptophan metabolism were altered following 24 h, but not 30 d of InCO 2 ; and 4 ) there were few changes in brainstem amine levels following 24 h or 30 d of increased InCO 2 . We conclude that these changes may contribute to initiating or maintaining respiratory neuroplasticity during chronic hypercapnia but alone do not account for ventilatory acclimatization to chronic increased InCO 2 .-Burgraff, N. J., Neumueller, S. E., Buchholz, K. J., LeClaire, J., Hodges, M. R., Pan, L., Forster, H. V. Brainstem serotonergic, catecholaminergic, and inflammatory adaptations during chronic hypercapnia in goats.

The swamp eel ( Monopterus albus ) uses its buccal cavity to air breathe, while the gills are strongly reduced. It burrows into mud during the dry season, is highly tolerant of air exposure, and experiences severe hypoxia both in its natural habitat and in aquaculture. To study the ability of M. albus to compensate for respiratory acidosis, we implanted catheters to sample both arterial blood and urine during hypercapnia (4% CO 2 ) in either water or air, or during whole-animal air exposure. These hypercapnic challenges caused an immediate reduction in arterial pH, followed by progressive compensation through a marked elevation of plasma HCO 3 - over the course of 72 h. There was no appreciable rise in urinary acid excretion in fish exposed to hypercapnia in water, although urine pH was reduced and ammonia excretion did increase. In the air-exposed fish, however, hypercapnia was attended by a large elevation of ammonia in the urine and a large rise in titratable acid excretion. The time course of the increased renal acid excretion overlapped with the time period required to elevate plasma HCO 3 - , and we estimate that the renal compensation contributed significantly to whole-body acid-base compensation., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2019. Published by The Company of Biologists Ltd.)

Carbon capture and storage technology was developed as a tool to mitigate the increased emissions of carbon dioxide by capture, transportation, injection and storage of CO 2 into subterranean reservoirs. There is, however, a risk of future CO 2 leakage from sub-seabed storage sites to the sea-floor sediments and overlying water, causing a pH decrease. The aim of this study was to assess effects of CO 2 -induced seawater acidification on fertilization success and early embryonic development of the sediment-burrowing bivalve Limecola balthica L. from the Baltic Sea. Laboratory experiments using a CO 2 enrichment system involved three different pH variants (pH 7.7 as control, pH 7.0 and pH 6.3, both representing environmental hypercapnia). The results showed significant fertilization success reduction under pH 7.0 and 6.3 and development delays at 4 and 9 h post gamete encounter. Several morphological aberrations (cell breakage, cytoplasm leakages, blastomere deformations) in the early embryos at different cleavage stages were observed., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

OBJECTIVE To evaluate effects of 2 levels of partial neuromuscular block on the ventilatory response to a hypercapnic challenge in anesthetized dogs and to evaluate effects of edrophonium for reversing partial neuromuscular block. ANIMALS 6 healthy adult Beagles. PROCEDURES Each dog was anesthetized twice with propofol and dexmedetomidine. End-tidal partial pressure of CO 2 (Petco 2 ), tidal volume (Vt), and peak inspiratory flow (PIF) were measured during breathing at rest. Maximal Vt and PIF (Vt MAX and PIF MAX , respectively) in response to a hypercapnic challenge consisting of 10% CO 2 inhaled for 1 minute were measured. Variables were measured before administration of atracurium (baseline), during moderate (train-of-four [TOF] ratio, 0.3 to 0.5) and mild (TOF ratio, 0.6 to 0.8) atracurium-induced neuromuscular block, and after neuromuscular block recovery (TOF ratio, ≥ 0.9) following administration of edrophonium or saline (0.9% NaCl) solution. Dogs for which any variable returned to < 80% of the baseline value were identified. RESULTS Partial neuromuscular block increased Petco 2 ; it impaired Vt at rest and Vt MAX but not PIF at rest and PIF MAX . All variables except Petco 2 returned to baseline values when the TOF returned to ≥ 0.9. After recovery from neuromuscular block, significantly more dogs had a Vt MAX < 80% of the baseline value when edrophonium was not administered. CONCLUSIONS AND CLINICAL RELEVANCE Partial neuromuscular block in anesthetized Beagles decreased spontaneous ventilation at rest and impaired the response to a hypercapnic challenge. Response to hypercapnic challenge might remain partially impaired after recovery of the TOF ratio to ≥ 0.9.

Objective: To evaluate the ability to assess laryngeal function and to diagnose unilateral laryngeal paralysis (uLP) via airway endoscopy and carbon dioxide (CO 2 ) stimulation., Study Design: Experimental study., Animals: Six healthy, adult beagles., Methods: Dogs were anesthetized with sevoflurane and dexmedetomidine. Laryngeal activity was observed via endoscopy placed through a laryngeal mask airway (LMA). The absolute and normalized glottic gap areas (AGGA and NGGA, respectively) and the glottic length (GL) were measured at inspiration and before and after surgically induced uLP. Measurements were obtained at eupnea and during hypercapnic hyperpnea produced by the administration of CO 2 . Values for each hemilarynx were also measured. Video recordings were observed by 2 surgeons who scored function as normal or uLP., Results: The AGGA and NGGA increased similarly during CO 2 administration in intact dogs and in dogs with uLP; the GL increased in dogs with uLP but not in intact dogs. The AGGA and NGGA of the intact hemilarynx increased more than those of the affected hemilarynx in dogs with uLP. uLP was correctly identified more frequently by observers at hypercapnic hyperpnea than during eupnea., Conclusion: The increase in AGGA and NGGA at peak inspiration during CO 2 administration was not limited by uLP, but asymmetry in hemilarynx AGGA and NGGA was observed in dogs with uLP. CO 2 administration facilitated the identification of uLP., Clinical Significance: Laryngeal endoscopy through an LMA coupled with administration of CO 2 in anesthetized dogs facilitates the observation of arytenoid function and may improve the diagnosis of naturally occurring mild laryngeal paralysis., (© 2018 The American College of Veterinary Surgeons.)

Hagfish are capable of tolerating extreme hypercapnia (> 30 Torr) by mounting substantial plasma [HCO 3 - ] (hypercarbia) to compensate for CO 2 -mediated acidosis. The goal of this study was to characterize the mechanistic hypercarbia-recovery strategies in the highly CO 2 tolerant hagfish. We exposed hagfish to hypercapnia (30 Torr) for 48 h and allowed a 24 h recovery period in normocapnic seawater. Within 8 h of the recovery period, the compensatory plasma [HCO 3 - ] load (~ 70 mmol L -1 ) was rapidly offloaded. While increases in both whole-animal HCO 3 - excretion and glomerular filtration were observed throughout recovery (2-8 h), neither can fully account for the observed rates of whole-animal HCO 3 - loss, which peaked at ~ 3.5 mmol kg -1  h -1 . Inhibition of carbonic anhydrase via acetazolamide revealed that the restoration of plasma [HCO 3 - ] from hypercapnia-induced hypercarbia is likely facilitated in a dualistic manner, initially relying on both carbonic anhydrase mediated CO 2 offloading and Cl - /HCO 3 - exchange processes, both of which are likely either upregulated or further activated as recovery progresses.

Nitrite and carbon dioxide are common environmental contaminants in the intensive aquaculture ponds used to farm clown knifefish (Chitala ornata) in the Mekong delta, Vietnam. Here we tested the hypothesis that hypercapnia reduces nitrite uptake across the gills, because pH regulation will reduce chloride uptake and hence nitrite uptake as the two ions compete for the same transport route via the branchial HCO 3 - /Cl - exchanger. Fish fitted with arterial catheters were exposed to normocapnic/normoxic water (control), nitrite (1 mM), hypercapnia (21 mmHg CO 2 ), or combined hypercapnia (acclimated hypercapnia) and nitrite for 96 h. Blood was sampled to measure acid-base status, haemoglobin derivatives and plasma ions. Plasma nitrite increased for 48 h, but levels stayed below the exposure concentration, and subsequently decreased as a result of nitrite detoxification to nitrate. The total uptake of nitrite (evaluated as [NO 2 - ] + [NO 3 - ]) was significantly decreased in hypercapnia, in accordance with the hypothesis. Methemoglobin and nitrosylhemoglobin levels were similarly lower during hypercapnic compared to normocapnic nitrite exposure. The respiratory acidosis induced by hypercapnia was half-compensated by bicarbonate accumulation in 96 h, which was mainly chloride-mediated (i.e. reduced Cl - influx via the branchial HCO 3 - /Cl - exchanger). Plasma osmolality and main ions (Na + , Cl - ) were significantly decreased by hypercapnia and by nitrite exposure, consistent with inhibition of active transport. We conclude that hypercapnia induces a long-lasting, and mainly chloride-mediated acid-base regulation that reduces the uptake of nitrite across the gills., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Respiratory acidosis, or primary hypercapnia, occurs when carbon dioxide production exceeds elimination via the lung and is mainly owing to alveolar hypoventilation. Concurrent increases in Paco 2 , decreases in pH and compensatory increases in blood HCO 3 - concentration are associated with respiratory acidosis. Respiratory acidosis can be acute or chronic, with initial metabolic compensation to increase HCO 3 - concentrations by intracellular buffering. Chronic respiratory acidosis results in longer lasting increases in renal reabsorption of HCO 3 - . Alveolar hypoventilation and resulting respiratory acidosis may also be associated with hypoxemia, especially evident when patients are inspiring room air (20.9% O 2 )., (Copyright © 2016 Elsevier Inc. All rights reserved.)

High carbon dioxide (CO2) concentrations in sea-water (ocean hypercapnia) can induce neurological, physiological and behavioural deficiencies in marine animals. Prediction of the onset and evolution of hypercapnia in the ocean requires a good understanding of annual variations in oceanic CO2 concentration, but there is a lack of relevant global observational data. Here we identify global ocean patterns of monthly variability in carbon concentration using observations that allow us to examine the evolution of surface-ocean CO2 levels over the entire annual cycle under increasing atmospheric CO2 concentrations. We predict that the present-day amplitude of the natural oscillations in oceanic CO2 concentration will be amplified by up to tenfold in some regions by 2100, if atmospheric CO2 concentrations continue to rise throughout this century (according to the RCP8.5 scenario of the Intergovernmental Panel on Climate Change). The findings from our data are broadly consistent with projections from Earth system climate models. Our predicted amplification of the annual CO2 cycle displays distinct global patterns that may expose major fisheries in the Southern, Pacific and North Atlantic oceans to hypercapnia many decades earlier than is expected from average atmospheric CO2 concentrations. We suggest that these ocean 'CO2 hotspots' evolve as a combination of the strong seasonal dynamics of CO2 concentration and the long-term effective storage of anthropogenic CO2 in the oceans that lowers the buffer capacity in these regions, causing a nonlinear amplification of CO2 concentration over the annual cycle. The onset of ocean hypercapnia (when the partial pressure of CO2 in sea-water exceeds 1,000 micro-atmospheres) is forecast for atmospheric CO2 concentrations that exceed 650 parts per million, with hypercapnia expected in up to half the surface ocean by 2100, assuming a high-emissions scenario (RCP8.5). Such extensive ocean hypercapnia has detrimental implications for fisheries during the twenty-first century.

Hypoxia in chicken embryos increases hematocrit (Hct), blood O2 content, and blood viscosity. The latter may limit O2 transport capacity (OTC) via increased peripheral resistance. Hct increase may result from increased nucleated red blood cell concentration ([RBC]) and mean corpuscular volume (MCV) or reduced plasma volume. We hypothesized changes in Hct, hemoglobin concentration ([Hb]), [RBC] and MCV and their effects on viscosity would reduce OTC. Five experimental treatments that increase Hct were conducted on day 15 embryos: 60min water submergence with 60min recovery in air; exposure to 15% O2 with or without 5% CO2 for 24 h with 6 h recovery; or exposure to 10% O2 with or without 5% CO2 for 120 min with 120 min recovery. Control Hct, [Hb], [RBC], MCV, and viscosity were approximately 26%, 9g%, 2.0 10(6)μL(-1), 130μm(3), and 1.6mPas, respectively. All manipulations increased Hct and blood viscosity without changing blood osmolality (276mmolkg(-1)). Increased viscosity was attributed to increased [RBC] and MCV in submerged embryos, but solely MCV in embryos experiencing 10% O2 regardless of CO2. Blood viscosity in embryos exposed to 15% O2 increased via increased MCV alone, and viscosity was constant during recovery despite increased [RBC]. Consequently, blood viscosity was governed by MCV and [RBC] during submergence, while MCV was the strongest determinant of blood viscosity in extrinsic hypoxia with or without hypercapnia. Increased Hct and blood O2 content did not compensate for the effect of increased viscosity on OTC during these challenges., (Copyright © 2015 Elsevier Inc. All rights reserved.)

A 5-hour-old, premature alpaca cria was presented with failure to nurse, weakness, hypoglycemia, hypercapnia, and respiratory distress. The cria was treated with 3 doses of fresh, crude equine surfactant, positive pressure ventilation, and supplemental intranasal oxygen. Recovery to discharge was uneventful, and the cria regained apparently normal respiratory function. Three years after hospital discharge, the alpaca was a healthy adult.

Chitons (class Polyplacophora) are benthic grazing molluscs with an eight-part aragonitic shell armature. The radula, a serial tooth ribbon that extends internally more than half the length of the body, is mineralised on the active feeding teeth with iron magnetite apparently as an adaptation to constant grazing on rocky substrates. As the anterior feeding teeth are eroded they are shed and replaced with a new row. The efficient mineralisation and function of the radula could hypothetically be affected by changing oceans in two ways: changes in seawater chemistry (pH and pCO2) may impact the biomineralisation pathway, potentially leading to a weaker or altered density of the feeding teeth; rising temperatures could increase activity levels in these ectothermic animals, and higher feeding rates could increase wear on the feeding teeth beyond the animals' ability to synthesise, mineralise, and replace radular rows. We therefore examined the effects of pH and temperature on growth and integrity in the radula of the chiton Leptochiton asellus. Our experiment implemented three temperature (∼10, 15, 20 °C) and two pCO2 treatments (∼400 μatm, pH 8.0; ∼2000 μatm, pH 7.5) for six treatment groups. Animals (n = 50) were acclimated to the treatment conditions for a period of 4 weeks. This is sufficient time for growth of ca. 7-9 new tooth rows or 20% turnover of the mineralised portion. There was no significant difference in the number of new (non-mineralised) teeth or total tooth row count in any treatment. Examination of the radulae via SEM revealed no differences in microwear or breakage on the feeding cusps correlating to treatment groups. The shell valves also showed no signs of dissolution. As a lineage, chitons have survived repeated shifts in Earth's climate through geological time, and at least their radulae may be robust to future perturbations., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Adult birds have a ventilatory equivalent (pulmonary ventilation-oxygen consumption ratio, V˙ E/ [Formula: see text] ) lower than mammals because of the superior gas exchange efficiency of their respiratory apparatus. In particular, adult Muscovy ducks (Cairina moschata) have been reported to have an extraordinary low ventilatory equivalent (~14mL STPD·mL BTPS(-1)). We asked if similar high efficiency was already apparent in duck hatchlings. Breathing pattern and V˙E were measured by the barometric technique and [Formula: see text] by an open-flow methodology in 1-day old Muscovy duck hatchlings (N=21); same measurements were performed on chicken hatchlings (N=21) for purpose of comparison. During air breathing V˙E/ [Formula: see text] was slightly, yet significantly, lower in ducklings (20.8) than in chicks (25.3), mostly because of a lower breathing frequency (f). The hatchlings of both species (N=14 per group) responded to inspired hypoxia (15 or 10% O2) or hypercapnia (2 or 4% CO2) with a clear hyperventilation; however, in ducklings the hypercapnic hyperventilation was smaller than in chicks because of a smaller increase in tidal volume and lower f. We conclude that duck and chicken hatchlings just a few hours old have the high ventilatory efficiency typical of birds, although possibly not as high as their adults. The low f and blunted V˙E response to hypercapnia of the newborn duck could be related to the aquatic habitat of the species. In such a case, it would mean that these characteristics are genetic traits, the phenotypic expression of which does not require diving experience., (© 2013.)

The mechanical ventilation of horses during anesthesia remains a crucial option for optimal anesthetic management, if the possible negative cardiovascular side effects are managed, because this species is prone to hypercapnia and hypoxemia. The combined use of capnography and pitot-based spirometry provide complementary information on ventilation and respiratory mechanics, respectively. This facilitates management of mechanical ventilation in conditions of changing respiratory system compliance (ie, laparoscopy) and when investigating new ventilatory strategies including alveolar recruitment maneuvers and optimization of positive expiratory pressure., (Copyright © 2013 Elsevier Inc. All rights reserved.)

The oceanic carbonate system is changing rapidly due to rising atmospheric CO(2), with current levels expected to rise to between 750 and 1,000 μatm by 2100, and over 1,900 μatm by year 2300. The effects of elevated CO(2) on marine calcifying organisms have been extensively studied; however, effects of imminent CO(2) levels on teleost acid-base and respiratory physiology have yet to be examined. Examination of these physiological processes, using a paired experimental design, showed that 24 h exposure to 1,000 and 1,900 μatm CO(2) resulted in a characteristic compensated respiratory acidosis response in the gulf toadfish (Opsanus beta). Time course experiments showed the onset of acidosis occurred after 15 min of exposure to 1,900 and 1,000 μatm CO(2), with full compensation by 2 and 4 h, respectively. 1,900-μatm exposure also resulted in significantly increased intracellular white muscle pH after 24 h. No effect of 1,900 μatm was observed on branchial acid flux; however, exposure to hypercapnia and HCO(3)(-) free seawater compromised compensation. This suggests branchial HCO(3)(-) uptake rather than acid extrusion is part of the compensatory response to low-level hypercapnia. Exposure to 1,900 μatm resulted in downregulation in branchial carbonic anhydrase and slc4a2 expression, as well as decreased Na(+)/K(+) ATPase activity after 24 h of exposure. Infusion of bovine carbonic anhydrase had no effect on blood acid-base status during 1,900 μatm exposures, but eliminated the respiratory impacts of 1,000 μatm CO(2). The results of the current study clearly show that predicted near-future CO(2) levels impact respiratory gas transport and acid-base balance. While the full physiological impacts of increased blood HCO(3)(-) are not known, it seems likely that chronically elevated blood HCO(3)(-) levels could compromise several physiological systems and furthermore may explain recent reports of increased otolith growth during exposure to elevated CO(2).

This paper reviews both the beneficial and adverse effects of permissive hypercapnic respiratory acidosis in critically ill newborn foals. It has been shown that partial carbon dioxide pressure (PCO2) above the traditional safe range (hypercapnia), has beneficial effects on the physiology of the respiratory, cardiovascular, and nervous system in neonates. In human neonatal critical care medicine permissive hypercapnic acidosis is generally well-tolerated by patients and is more beneficial to their wellbeing than normal carbon dioxide (CO2) pressure or normocapnia. Even though adverse effects of hypercapnia have been reported, especially in patients with central nervous system pathology and/or chronic infection, critical care clinicians often artificially increase PCO2 to take advantage of its positive effects on compromised neonate tissues. This is referred to as therapeutic hypercapnia. Hypercapnic respiratory acidosis is common in critically ill newborn foals and has traditionally been considered as not beneficial. A search of online scientific databases was conducted to survey the literature on the effects of hypercapnia in neonates, with emphasis on newborn foals. The dynamic status of safety levels of PCO2 and data on the effectiveness of different carbon dioxide levels are not available for newborn foals and should be scientifically determined. Presently, permissive hypercapnia should be implemented or tolerated cautiously in compromised newborn foals and its use should be based on relevant data from adult horses and other species.

Hypoxia inducible factor (HIF) is a transcription factor that under low environmental oxygen regulates the expression of suites of genes involved in metabolism, angiogenesis, erythropoiesis, immune function, and growth. Here, we isolated and sequenced partial cDNAs encoding hif-α and arnt/hif-β from the Atlantic blue crab, Callinectes sapidus, an estuarine species that frequently encounters concurrent hypoxia (low O(2)) and hypercapnia (elevated CO(2)). We then examined the effects of acute exposure (1h) to hypoxia (H) and hypercapnic hypoxia (HH) on relative transcript abundance for hif-α and arnt/hif-β in different tissues (glycolytic muscle, oxidative muscle, hepatopancreas, gill, and gonads) using quantitative real-time RT-PCR. Our results indicate that hif-α and arnt/hif-β mRNAs were constitutively present under well-aerated normoxia (N) conditions in all tissues examined. Further, H and HH exposure resulted in both tissue-specific and muscle fiber type-specific effects on relative hif-α transcript abundance. In the gill and glycolytic muscle, relative hif-α mRNA levels were significantly lower under H and HH, compared to N, while no change (or a slight increase) was detected in oxidative muscle, hepatopancreas and gonadal tissues. H and HH did not affect relative transcript abundance for arnt/hif-β in any tissue or muscle fiber type. Thus, in crustaceans the HIF response to H and HH appears to involve changes in hif transcript abundance, with variation in hif-α and arnt/hif-β transcriptional dynamics occurring in both a tissue- and muscle fiber type-dependent manner., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objective: To test the hypothesis that hypercapnic hyperpnea produced using endotracheal insufflation with 5-10% CO(2) in oxygen could be used to shorten anesthetic recovery time in horses, and that recovery from sevoflurane would be faster than from isoflurane., Study Design: Randomized crossover study design., Animals: Eight healthy adult horses., Methods: After 2 hours' administration of constant 1.2 times MAC isoflurane or sevoflurane, horses were disconnected from the anesthetic circuit and administered 0, 5, or 10% CO(2) in balance O(2) via endotracheal tube insufflation. End-tidal gas samples were collected to measure anesthetic washout kinetics, and arterial and venous blood samples were collected to measure respiratory gas partial pressures. Horses recovered in padded stalls without assistance, and each recovery was videotaped and evaluated by reviewers who were blinded to the anesthetic agent and insufflation treatment used., Results: Compared to isoflurane, sevoflurane caused greater hypoventilation and was associated with longer times until standing recovery. CO(2) insufflation significantly decreased anesthetic recovery time compared to insufflation with O(2) alone without significantly increasing PaCO(2) . Pharmacokinetic parameters during recovery from isoflurane with CO(2) insufflation were statistically indistinguishable from sevoflurane recovery without CO(2). Neither anesthetic agent nor insufflation treatment affected recovery quality from anesthesia., Conclusions and Clinical Relevance: Hypercapnic hyperpnea decreases time to standing without influencing anesthetic recovery quality. Although the lower blood gas solubility of sevoflurane should favor a shorter recovery time compared to isoflurane, this advantage is negated by the greater respiratory depression from sevoflurane in horses., (© 2012 The Authors. Veterinary Anaesthesia and Analgesia. © 2012 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesiologists.)

Fish exposed to elevated water CO(2) experience a rapid increase in blood CO(2) levels (hypercapnia), resulting in acidification of both intra- and extra-cellular compartments. While the mechanisms associated with extracellular pH regulation have been well explored, much less is known about intracellular pH (pH(i)) regulation. There is great interest in developing non-animal models for research. One such model is the rainbow trout hepatoma cell line (RTH 149), which has been used to study a wide range of topics; however, no studies have investigated its potential use in pH(i) regulation. Employing the pH-sensitive fluoroprobe BCECF, the present study examined pH(i) regulation in RTH 149 under normocapnia and during extracellular acidification induced by either elevated CO(2) or 1 M HCl. During exposure to hypercapnia, RTH 149 cells were acidified without recovery as long as the elevated CO(2) was maintained. In addition, rates of pH(i) recovery from NH(4)Cl-induced acidosis were significantly lower in cells exposed to hypercapnia or HCl compared to that in normocapnic cells, indicating that elevated CO(2) indirectly impeded pH(i) recovery through a reduction in pH(e) and/or pH(i). Moreover, pH(i) regulation in RTH 149 was EIPA-sensitive, suggesting that an NHE may be involved. Overall, RTH 149 may have the potential for identifying transporters likely to play a role in pH(i) regulation in fish. However, it should not be used as a complete replacement for in vivo studies, especially to quantify acid-base regulatory ability at whole animal level, since RTH 149 appeared to have enhanced pH(i) recovery rates relative to primary hepatocytes.

History: A 3-year-old, 400 kg, gelding Quarter Horse was presented for investigation of epistaxis., Physical Examination: The horse was bright, alert and responsive with rectal temperature, heart rate and respiration rate within normal limits., Management: During a second general anaesthetic for surgical treatment of guttural pouch mycosis by balloon-tipped catheter occlusion of the right major palatine artery and ligation of the right external carotid artery, signs consistent with hyperkalaemic periodic paralysis (HYPP) were exhibited. These included concurrent hyperkalaemia, hypercapnoea, sinus tachycardia, and muscle fasciculations in the presence of normothermia. Stress associated with an acute haemorrhage pre-operatively, and intra-operative hypercapnoea may have precipitated the episode. There were no signs of HYPP during a general anaesthetic, 1 week earlier, when an initial attempt at surgical treatment of guttural pouch mycosis was performed. Treatment consisted of fluid therapy and administration of calcium gluconate (0.1-0.2 mg kg(-1) minute(-1)), dextrose 5% (5 mL kg(-1) hour(-1)) and insulin (0.05 IU kg(-1)). Treatment resulted in the resolution of clinical signs and an uneventful recovery., Follow-Up: The diagnosis of HYPP was confirmed by DNA analysis post-operatively., Conclusions: Clinical cases of intra-operative HYPP can present despite a previous history of uneventful general anaesthesia. Rapid diagnosis and treatment can result in the successful management of HYPP. This report documents an unusual presentation of HYPP, a disease that remains present in the Quarter Horse population., (© 2011 The Authors. Veterinary Anaesthesia and Analgesia © 2011 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesiologists.)

Objective: To evaluate the effects of various combinations of PaCO2 and PaO2 values on brain morphometrics., Animals: 6 healthy adult dogs., Procedures: A modified Latin square design for randomization was used. Dogs were anesthetized with propofol (6 to 8 mg/kg, IV), and anesthesia was maintained with isoflurane (1.7%) and atracurium (0.2 mg/kg, IV, q 30 min). Three targeted values of PaCO2 (20, 40, and 80 mm Hg) and 2 values of PaO2 (100 and 500 mm Hg) were achieved in each dog, yielding 6 combinations during a single magnetic resonance (MR) imaging session. When the endpoints were reached, dogs were given at least 5 minutes for physiologic variables to stabilize before T1-weighted MR images were obtained. Total brain volume (TBV) and lateral ventricular volume (LVV) were calculated from manually drawn contours of areas of interest by use of a software program, with each dog serving as its own control animal. Three blinded investigators subjectively evaluated the lateral ventricular size (LVS) and the cerebral sulci width (CSW). Brain morphometric values were compared among the target blood gas states., Results: No significant differences in TBV were found among target states. The LVV was significantly greater during hypocapnia, compared with hypercapnia at the same PaO2 value. With regard to the subjective evaluations, there were no significant differences among evaluators or among combinations of PaO2 and PaCO2 values., Conclusions and Clinical Relevance: The changes observed in LVV during hypocapnia and hypercapnia may serve as a potential confounding factor when neuromorphometric evaluations are performed in anesthetized dogs.

Objective: To describe the successful management of an alpaca with severe hypoventilation and hypercapnia, suspected to be secondary to an anesthesia-related event., Case Summary: A 3-year-old, female alpaca underwent a routine eye enucleation under general anesthesia after traumatic globe perforation. Severe hypoventilation and associated hypercapnia developed postoperatively resulting in a severe primary respiratory acidosis. The awake alpaca was supported with positive-pressure ventilation for approximately 20 hours before successful weaning. Recovery to hospital discharge occurred over the subsequent 5 days with the alpaca regaining apparently normal respiratory function., New or Unique Information Provided: To the knowledge of the authors, this is the first report describing positive-pressure ventilation of an alpaca in the veterinary literature. In this case of severe hypoventilation, ventilatory support was essential to the positive outcome. As South American camelids continue to increase in popularity there may be an increased demand for high-quality and sophisticated veterinary care for these animals. Mechanical ventilation can be used to help restore and maintain normal PO2, PCO2, and respiratory acid-base status in alpacas with ventilatory dysfunction.

Experiments were conducted on adult rainbow trout (Oncorhynchus mykiss) to test the hypothesis that SLC9 Na+/H+ exchangers (SLC9A2, NHE2; and SLC9A3, NHE3) on the gill epithelium are localized specifically to a subset of mitochondria-rich cells (MRCs) that are unable to bind peanut lectin agglutinin (PNA). This cell type, termed the PNA- MRC, is a sub-type of MRC believed to function in Na+ uptake and acid excretion. A technique using biotinylated PNA was used to distinguish between the PNA- and PNA+ MRCs on fixed gill sections. In contrast to expectations, both NHE2 (mRNA) and NHE3 (protein) were confined to cells enriched with Na+/K+-ATPase and capable of binding PNA. Thus, in trout, NHE2 and NHE3 are localized to PNA+ MRCs, the cells previously believed to be responsible for Cl- uptake and base excretion. Levels of mRNA for NHE2, the predominant isoform in the gill, were increased during 72 h of hypercapnic acidosis; NHE3 mRNA and protein levels were unaffected. Because plasma cortisol levels were increased during hypercapnia (from 35.3+/-9.4 to 100.1+/-30.9 ng ml(-1)), the effects of experimentally elevated cortisol levels on NHE expression were investigated. The elevation of plasma cortisol using intraperitoneal implants caused a significant increase in NHE2 mRNA expression without affecting NHE3 mRNA or protein abundance. Thus, we suggest that NHE2 contributes to acid-base regulation during hypercapnia owing to its transcriptional regulation by cortisol. The finding of NHE expression in PNA+ MRCs is discussed with reference to current models of ionic and acid-base regulation in teleost fish.

Background: Despite a lack of data regarding their efficacy, both caffeine and doxapram have been recommended for treatment of hypercapnia in equine neonates with central nervous system damage., Hypothesis: Caffeine and doxapram alleviate hypercapnia in foals with hypoxic-ischemic encephalopathy., Animals: Sixteen foals treated with either caffeine (n = 8) or doxapram (n = 8)., Methods: Information on age, body temperature, heart rate, respiratory rate, arterial blood gas parameters, duration of therapy, and outcome was abstracted from each medical record., Results: Therapy with doxapram resulted in a significant decrease in partial pressure of carbon dioxide (PaCO2 [P= .004]), bicarbonate concentration (P= .002), and base excess (P= .005) compared with baseline values but failed to correct acidemia. In contrast, administration of caffeine did not result in significant changes from baseline values. The percentage decrease in PaCO2 and bicarbonate concentration was significantly greater in foals treated with doxapram than in foals treated with caffeine (P= .004). The proportions of foals that achieved the targeted PaCO2 (< or = 50 mmHg) were significantly higher in foals treated with doxapram than in foals treated with caffeine (P= .029). The proportion of survivors in the 2 treatment groups was not significantly different., Conclusions and Clinical Importance: Doxapram is more effective than caffeine for rapid correction of hypercapnia in foals with hypoxic-ischemic encephalopathy.

Pigs are increasingly used as in vivo models in neuroscience, including studies using positron emission tomography. During anesthesia, cerebral blood flow (CBF) and cerebral blood volume (CBV) are mainly regulated by the partial pressure of CO2 (pCO2) in arterial blood. We sought to determine the effects of increased arterial pCO2 (hypercapnia) on CBF and CBV in anesthetized domestic pigs. We anesthetized 4 pigs and manipulated the tidal volume of the ventilator to different pCO2 levels. Baseline pCO2 was on average 6.5 kPa (n = 9 periods) and hypercapnia pCO2 ranged from 11 to 20 kPa, mean 18.5 kPa (n = 9 periods). Series of dynamic PET scans with H(2)15O (CBF measurements) and C15O (CBV measurements) were performed. CBF increased on average 54%, from mean 0.48 ml blood/min/ml brain tissue during normoxia to 0.74 ml blood/min/ml brain tissue during hypercapnia. CBV increased 41% from mean 0.061 ml blood/ml brain tissue (n = 6) during normoxia to 0.086 ml blood/ml brain tissue (n = 6) during hypercapnia. Our observations indicate that pCO2 levels have a major influence on porcine CBF and CBV and should be controlled in studies where a constant level is crucial.

To investigate whether the biological toxicity of aquatic hypercapnia is due to the direct effects of CO2 or to the effects of acidification of seawater by CO2, the Japanese flounder (Paralichthys olivaceus) was subjected to seawater equilibrated with a gas mixture of air containing 5% CO2 (pH 6.18) or seawater acidified to the same pH with 1 N H2SO4. All the fish died within 72 h in the CO2 exposure group, whereas no mortality occurred in the acid group. Acid-base parameters as well as plasma ion concentrations were severely perturbed in the CO2 exposure group, whereas they were minimally affected in the acid group. These results clearly demonstrate that the mortality in the CO2 group is a direct result of the elevated levels of dissolved CO2 and not to the effects of the reduced water pH.

Spontaneous ventilation during positive pressure ventilation was observed in a 4-year-old DSH cat maintained under general anesthesia with isoflurane delivered with a nonrebreathing system. This was accompanied by an increase in heart rate and blood pressure. On investigation, neither an inadequate plane of anesthesia, nor hypoxemia, nor hyperthermia was present. The nonrebreathing system was replaced and the hypercapnia resolved. A defect in the inner fresh gas delivery tube of the Bain system was identified. A simple and quick test is described which can be performed to verify the integrity of the inner tube of the Bain breathing circuit.

A mature horse developed acute signs of bronchoconstriction causing hypoxemia and hypercapnia during anesthesia for computerized tomography of the maxillary sinus after i.v. administration of diatrizoate contrast medium. The horse was treated with aerosolized albuterol, atropine, and oxygen insufflation and recovered uneventfully despite severe hypoxemia and low hemoglobin saturation. The horse's condition continued to improve after treatment, and the horse was discharged with no further complications. Caution is advised with the use of contrast media in anesthetized horses.

Objective: To determine frequency and severity of postanesthetic hypoxemia and hypercarbia in healthy dogs undergoing elective ovariohysterectomy or castration and given butorphanol or hydromorphone for analgesia., Design: Prospective trial., Animals: 0 healthy dogs weighing > 10 kg (22 lb)., Procedure: Dogs were anesthestized with acepromazine, glycopyrrolate, thiopental, and isoflurane, and butorphanol (n = 10) or hydromorphone (10) was used for perioperative analgesia. Arterial blood gas analyses were performed 10 and 30 minutes and 1, 2, 3, and 4 hours after extubation., Results: In dogs that received hydromorphone, mean PaCO2 was significantly higher, compared with the preoperative value, 10 and 30 minutes and 1, 2, and 3 hours after extubation. Mean PaCO2 was significantly higher in dogs given hydromorphone rather than butorphanol 10 and 30 minutes and 1 and 2 hours after extubation. Mean PaO2 was significantly lower, compared with preoperative values, 30 minutes and 1 and 2 hours after extubation in dogs given hydromorphone and 30 minutes after extubation in dogs given butorphanol. Mean PaO2 was significantly lower in dogs given hydromorphone rather than butorphanol 1 hour after extubation. Four dogs had PaO2 < 80 mm Hg 1 or more times after extubation., Conclusions and Clinical Relevance: Results suggest that administration of hydromorphone to healthy dogs undergoing elective ovariohysterectomy or castration may result in transient increases in PaCO2 postoperatively and that administration of hydromorphone or butorphanol may result in transient decreases in PaO2. However, increases in PaCO2 and decreases in PaO2 were mild, and mean PaCO2 and PaO2 remained within reference limits.

Severe acute hypercarbia occurred in a cat and 2 dogs as a result of anesthesia machine malfunction. In each case, the anesthesia machine had been checked by the anesthesia technician and clinician, and no problems were found. After it was noticed that the same machine had been used on each animal, further investigation revealed an expiration valve that was functional with large breaths or positive pressure ventilation but was not functional with small breaths with low peak inspiratory flow. Rebreathing of expired carbon dioxide occurred, and the patients subsequently became severely hypercarbic. Recovery from anesthesia was prolonged in 2 animals, and cardiac and respiratory arrest occurred in the third. Hypercarbia from rebreathing can be detected through the use of blood gas analysis or end-tidal carbon monoxide monitoring.

Acute hypoxia can cause massive fish and shellfish mortality. Less clear is the role that chronic sublethal hypoxia might play in aquatic animal health. This study tested whether production of reactive oxygen species (ROS) and bactericidal activity of fish phagocytic cells are suppressed under the conditions of decreased oxygen and pH and increased carbon dioxide which occur in the blood and tissue of animals exposed to sublethal hypoxia. Anterior head kidney (AHK) cells of the mummichog, Fundulus heteroclitus, were exposed in parallel to normoxic (pO2=45 torr, pCO2=3.8 torr, pH=7.6) or hypoxic (pO2=15 torr, pCO2=8.0 torr, pH=7.0) conditions and stimulated with a yeast cell wall extract, zymosan. or live Vibrio parahaemolyticus. Hypercapnic hypoxia suppressed zymosan-stimulated ROS production by 76.0% as measured in the chemiluminescence assay and by 58.5% in the nitroblue tetrazolium (NBT) assay. The low O2, high CO2 and low pH conditions also suppressed superoxide production by 75.0 and 47.3% as measured by the NBT assay at two different challenge ratios of cells:bacteria (1:1 and 1:10, respectively). In addition to its effects on ROS production, hypercapnic hypoxia also reduced bactericidal activity by 23.6 and 72.5% at the 1:1 and 1:10 challenge ratios, respectively. Low oxygen levels alone (pO2=15 torr, pCO2=0.76 torr, pH=7.6) did not significantly compromise the killing activity of cells challenged with equal numbers of V. parahaemolyticus. At the higher 1:10 AHK:bacteria challenge ratio, low oxygen caused a small (26.3%) but significant suppression of bactericidal activity as compared to aerial conditions (pO2=155 torr, pCO2=0.76 torr, pH=7.6). This study demonstrates that while hypoxia alone has detrimental effects on immune function, suppression of phagocytic cell activity is compounded by naturally occurring conditions of hypercapnia and low pH, creating conditions that might be exploited by opportunistic pathogens. These results indicate that the adverse health effects of chronic hypercapnic hypoxia might greatly exceed the effects of low oxygen alone.

Objective: To determine effects of hypercapnia on arrhythmias in ducks anesthetized with halothane., Animals: 12 ducks, 6 to 8 months old, weighing 1.1 to 1.6 kg., Procedures: Each duck was anesthetized with a 1.5% mixture of halothane in oxygen, and anesthetic depth was stabilized during a 20-minute period. We added CO2 to the inspired oxygen to produce CO2 partial pressures of 40, 60, and 80 mm Hg in the inspired gas mixture.The CO2 partial pressure was increased in a stepwise manner. When arrhythmias were not evident during inhalation of the gas mixture at a specific CO2 partial pressure, the CO2 partial pressure was maintained for 10 minutes before a sample was collected for blood gas analysis. When arrhythmias were detected, a sample for blood gas analysis was collected after the CO2 partial pressure was maintained for at least 2 minutes, and CO2 inhalation then was terminated., Results: During the stabilization period, PaCO2 (mean +/- SD) was 33 +/- 5 mm Hg,and arrhythmias were not detected. In 6 ducks, arrhythmias such as unifocal and multifocal premature ventricular contractions developed during inhalation of CO2. Mean PaCO2 at which arrhythmias developed was 67 +/- 12 mm Hg. In 5 of 6 ducks with arrhythmias, the arrhythmias disappeared after CO2 inhalation was terminated., Conclusion and Clinical Relevance: Analysis of data from this study indicated that hypercapnia can lead to arrhythmias in ducks during halothane-induced anesthesia. Thus, ventilatory support to maintain normocapnia is important for managing ducks anesthetized with halothane.

The complications and mortality associated with anesthesia of dogs and cats in a university teaching hospital were determined. During one year, 2,556 dogs and 683 cats were anesthetized by the anesthesia service. Hypotension occurred in 179 (7%) dogs and 58 (8.5%) cats. Cardiac dysrhythmias occurred in 64 (2.5%) dogs and 12 (1.8%) cats. Transfusions were required in 31 (1.2%) dogs. Hypercapnea occurred in 33 (1.3%) dogs and one (less than 1%) cat. Hypoxemia occurred in 14 (0.5%) dogs. Anesthetic complications, as defined, occurred in 12.0% of dogs and 10.5% of cats, while deaths associated with the perianesthetic period occurred in 0.43% of dogs and 0.43% of cats.

Objective: To describe alterations in respiratory and cardiovascular variables during diagnostic thoracoscopy, using bilateral hemithorax ventilation with sustained pneumothorax., Animals: 7 adult dogs., Procedure: Each dog was anesthetized and instrumented for 2 episodes of cardiopulmonary monitoring that were performed at an interval of more than 14 days. The first anesthetic episode served as a control procedure for the thoracoscopy treatment performed during the second anesthetic episode. Multiple cardiopulmonary variables were evaluated by comparing changes from baseline values within treatments and between treatments., Results: Arterial oxygen tension decreased significantly from baseline values during thoracoscopy but was unchanged during sham treatment. Arterial carbon dioxide tension, clinical shunt fraction, and systemic mean arterial pressure increased during thoracoscopy. In contrast, these variables were unaffected by the sham treatment. Heart rate and cardiac index increased during sham and thoracoscopy treatments; however, the increase was significantly greater during thoracoscopy. Total peripheral vascular resistance significantly decreased from baseline values for both treatments, but the decrease was greater during thoracoscopy. Significant changes were not observed for oxyhemoglobin saturation or pulmonary vascular resistance during either treatment. Dogs recovered without major clinical complications., Conclusions: Significant changes were found for several cardiopulmonary variables during bilateral hemithorax ventilation with sustained pneumothorax for diagnostic thoracoscopy of clinically normal dogs., Clinical Relevance: Diagnostic thoracoscopy with bilateral hemithorax ventilation and sustained pneumothorax is well tolerated in clinically normal dogs and may provide a diagnostic modality enabling intrathoracic procedures with less morbidity than thoracotomy for dogs with intrathoracic disease.

Some metabolic and endocrine effects of hypercapnia were studied in six ponies during halothane anaesthesia with neuromuscular blockade and controlled ventilation. Each was anaesthetised twice, once with a 40-minute-period of hypercapnia (10 kPa) and once when normocapnia (5.3 kPa) was maintained throughout two hour's anaesthesia. Routine cardiovascular monitoring was performed and blood samples were taken for assay of cortisol, insulin, glucose, lactate, muscle and liver enzymes and total protein. Anaesthesia induced hypotension and lacticacidaemia which were slightly ameliorated during hypercapnia. Hyperglycaemia was more marked during hypercapnia. Plasma cortisol increased in a similar manner in both groups and insulin tended to decrease. There were no major changes in the other variables measured. It was concluded that 40 minutes of hypercapnia during halothane anaesthesia in ponies may have improved perfusion and did not markedly alter the stress response.

Objective: To compare the efficacy of positive pressure ventilation applied through a mask versus an endotracheal tube, using anesthetized/paralyzed foals as a model for foals with hypoventilation., Animals: Six 1-month-old foals., Procedure: A crossover design was used to compare the physiologic response of foals to 2 ventilatory techniques, noninvasive mask mechanical ventilation (NIMV) versus endotracheal mechanical ventilation (ETMV), during a single period of anesthesia and paralysis. Arterial pH, PaO2, PaCO2, oxygen saturation, end-tidal CO2 tension, airway pressures, total respiratory system resistance, resistance across the upper airways (proximal to the midtracheal region), and positive end-expiratory pressures (PEEP) were measured. Only tidal volume (VT; 10, 12.5, and 15 ml/kg of body weight) or PEEP (7 cm of H2O) varied., Results: Compared with ETMV, use of NIMV at equivalent VT resulted in PaCO2 and pH values that were significantly higher, but PaO2 was only slightly lower. Between the 2 methods, peak airway pressure was similar, but peak expiratory flow was significantly lower and total respiratory resistance higher at each VT for NIMV. Delivery of PEEP (7 cm of H2O) was slightly better for ETMV (7.1 +/- 1.3 cm of H2O) than for NIMV (5.6 +/- 0.6 cm of H2O)., Conclusion: These data suggest that use of NIMV induces similar physiologic effects as ETMV, but the nasal cavities and mask contribute greater dead space, manifesting in hypercapnia. Increasing the VT used on a per kilogram of body weight basis, or the use of pressure-cycled ventilation might reduce hypercapnia during NIMV., Clinical Relevance: Use of NIMV might be applicable in selected foals, such as those with hypoventilation and minimal changes in lung compliance, during weaning from endotracheal mechanical ventilation, or for short-term ventilation in weak foals.