The influence of hypoxaemia, hypotension and hypercapnia (among other factors) on quality of recovery from general anaesthesia in horses.

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 [PaO2 < 60 mmHg (7.99 kPa)], hypotension (mean arterial pressure < 70 mmHg for at least 15 minutes) and hypercapnia [PaCO2 > 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.

Effects of Butorphanol on Respiration in White Rhinoceros (Ceratotherium simum) Immobilized with Etorphine-Azaperone.

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.

Comparative study of ventilation techniques with supraglottic airway devices in cats: volume-controlled vs pressure-controlled techniques.

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 cmH2O) were randomly applied with a minute ventilation of 100 ml/kg/min. Various parameters, such as blood pressure, gas leakage, end-tidal CO2 (ETCO2) 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.

Effects of 2 modes of positive pressure ventilation on respiratory mechanics and gas exchange in foals.

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 (PaO2 ), respiratory rate, and tidal volume. Continuous positive airway pressure was associated with improved PaO2 , 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 PaO2 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.

Some cardiopulmonary effects of capnoperitoneum in anesthetized guinea pigs (Cavia porcellus): spontaneous ventilation versus intubation and mechanical ventilation.

OBJECTIVE: To compare cardiopulmonary variables and blood gas analytes in guinea pigs (Cavia porcellus) during anesthesia with and without abdominal carbon dioxide (CO2) 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 CO2 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 CO2 (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 CO2 in cranial vena cava blood (PvCO2) than nonintubated guinea pigs. An IAP of 6 mmHg resulted in a significantly higher PvCO2 (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.

Inclusion of airway pressure release ventilation in the management of respiratory failure and refractory hypercapnia in a dog.

OBJECTIVE: To describe the use of airway pressure release ventilation (APRV) to relieve hypercapnia in a dog undergoing mechanical ventilation. CASE SUMMARY: A 3-month-old male Shar-Pei mix presented to the emergency department with suspected noncardiogenic pulmonary edema. Due to severe hypercapnia, mechanical ventilation was initiated. The hypercapnia failed to improve with conventional pressure control mechanical ventilation, bronchodilator administration, suctioning, or endotracheal tube replacement. The dog was transitioned to APRV and maintained in this mode for 36 hours. A modified APRV protocol in which inverse inspiratory to expiratory ratios ranged from 4.3:1 to 6.0:1 was utilized, resulting in a drastic improvement in the patient's hypercapnia. The patient eventually was transitioned off the ventilator, and no respiratory abnormalities have been noted at subsequent recheck examinations. NEW OR UNIQUE INFORMATION PROVIDED: This case documents the first use of APRV to relieve refractory hypercapnia in a dog undergoing mechanical ventilation and is one of the only recorded cases of using APRV for this purpose in the medical literature at large. APRV may be considered in cases of hypercapnia when traditional therapies fail, although caution is warranted as this mode of ventilation can also worsen hypercapnia.

The use of caffeine as a respiratory stimulant in a cat.

OBJECTIVE: To report the use of caffeine as a respiratory stimulant in a cat with hypoventilation. CASE SUMMARY: A cat was mechanically ventilated due to persistent hypercapnia (Pet co2  > 75 mm Hg) following median sternotomy and thymectomy. After 3 days of mechanical ventilatory support, the cat would initiate breaths but failed weaning due to persistent hypercapnia. Following administration of intravenous caffeine (total 12 mg/kg over 24 h), respiratory and mental status rapidly improved. The cat was subsequently extubated and able to maintain Pvco2  < 50 mm Hg. The cat was later diagnosed with myasthenia gravis. Quality of life 13 months after discharge was reported as excellent by her owner. NEW OR UNIQUE INFORMATION PROVIDED: Caffeine may be considered as a respiratory stimulant in cats with hypoventilation.

Cardiovascular effects of intravenous pimobendan in dogs with acute respiratory acidosis.

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 (Paco2 35-40 mm Hg) and hypercapnia (Paco2 90-110 mm Hg). Eucapnia was maintained by positive pressure ventilation and hypercapnia was induced by adding exogenous CO2 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/m2 [mean ± SE], low: 5.0 ± 0.4 L/kg/m2 , high: 5.8 ± 0.5 L/kg/m2 , P < 0.001) and hypercapnia (baseline: 4.9 ± 0.5 L/kg/m2 , low: 5.8 ± 0.5 L/kg/m2 , high: 6.2 ± 0.5 L/kg/m2 , 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.

Clinicopathological factors associated with the presence of hypercapnia at admission in hospitalised cats with decompensated chronic kidney disease.

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 CO2 (PvCO2), 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 (PvCO2 ≥ 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.

Hypercapnia and hyperlactatemia were positively associated with higher-grade arrhythmias during peak exercise in horses during poor performance evaluation on a high-speed treadmill.

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 CO2 (PaCO2; P = 0.008) and lactate (P = 0.031) were significantly associated with arrhythmias occurring at peak exercise, but not immediately post-exercise. As PaCO2 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 PaCO2 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 PaCO2 and lactate values increased further, the severity of those arrhythmias increased.

Brainstem serotonergic, catecholaminergic, and inflammatory adaptations during chronic hypercapnia in goats.

Despite the prevalence of CO2 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 CO2 (InCO2) leads to a steady-state ventilation that exceeds the level predicted by the sustained acidosis and the acute CO2/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 InCO2 increased IL-1ß 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 InCO2; 3) markers of tryptophan metabolism were altered following 24 h, but not 30 d of InCO2; and 4) there were few changes in brainstem amine levels following 24 h or 30 d of increased InCO2. 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 InCO2.-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.

Ventilatory responses of the clown knifefish, Chitala ornata, to arterial hypercapnia remain after gill denervation.

The aim of this study was to corroborate the presence of CO2/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 CO2 mixed with air were injected into the air-breathing organ (ABO) of one group of intact fish to elevate internal PCO2 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 PCO2 and decrease blood pH). Air-breathing frequency, gill ventilation frequency, heart rate and arterial PCO2 and pH were recorded during all treatments. The CO2 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 PCO2 and decreases in blood pH, the modest changes in arterial PCO2/pH in the acetazolamide treatment produced the greatest increases in air-breathing frequency. These results strengthen the evidence that internal CO2/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.

Renal acid excretion contributes to acid-base regulation during hypercapnia in air-exposed swamp eel (Monopterus albus).

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% CO2) 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 HCO3- 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 HCO3-, and we estimate that the renal compensation contributed significantly to whole-body acid-base compensation.

Impact of environmental hypercapnia on fertilization success rate and the early embryonic development of the clam Limecola balthica (Bivalvia, Tellinidae) from the southern Baltic Sea - A potential CO2 leakage case study.

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 CO2 into subterranean reservoirs. There is, however, a risk of future CO2 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 CO2-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 CO2 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.

Effects of two levels of partial neuromuscular block with atracurium on the ventilatory response to hypercapnia in anesthetized Beagles.

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 CO2 (Petco2), tidal volume (Vt), and peak inspiratory flow (PIF) were measured during breathing at rest. Maximal Vt and PIF (VtMAX and PIFMAX, respectively) in response to a hypercapnic challenge consisting of 10% CO2 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 Petco2; it impaired Vt at rest and VtMAX but not PIF at rest and PIFMAX. All variables except Petco2 returned to baseline values when the TOF returned to ≥ 0.9. After recovery from neuromuscular block, significantly more dogs had a VtMAX < 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.

Laryngeal mask airway and transient hypercapnic hyperpnea for video-endoscopic assessment of unilateral laryngeal paralysis in dogs.

OBJECTIVE: To evaluate the ability to assess laryngeal function and to diagnose unilateral laryngeal paralysis (uLP) via airway endoscopy and carbon dioxide (CO2 ) 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 CO2 . 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 CO2 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 CO2 administration was not limited by uLP, but asymmetry in hemilarynx AGGA and NGGA was observed in dogs with uLP. CO2 administration facilitated the identification of uLP. CLINICAL SIGNIFICANCE: Laryngeal endoscopy through an LMA coupled with administration of CO2 in anesthetized dogs facilitates the observation of arytenoid function and may improve the diagnosis of naturally occurring mild laryngeal paralysis.

Dropping the base: recovery from extreme hypercarbia in the CO2 tolerant Pacific hagfish (Eptatretus stoutii).

Hagfish are capable of tolerating extreme hypercapnia (> 30 Torr) by mounting substantial plasma [HCO3-] (hypercarbia) to compensate for CO2-mediated acidosis. The goal of this study was to characterize the mechanistic hypercarbia-recovery strategies in the highly CO2 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 [HCO3-] load (~ 70 mmol L-1) was rapidly offloaded. While increases in both whole-animal HCO3- excretion and glomerular filtration were observed throughout recovery (2-8 h), neither can fully account for the observed rates of whole-animal HCO3- loss, which peaked at ~ 3.5 mmol kg-1 h-1. Inhibition of carbonic anhydrase via acetazolamide revealed that the restoration of plasma [HCO3-] from hypercapnia-induced hypercarbia is likely facilitated in a dualistic manner, initially relying on both carbonic anhydrase mediated CO2 offloading and Cl-/HCO3- exchange processes, both of which are likely either upregulated or further activated as recovery progresses.

The effects of elevated environmental CO2 on nitrite uptake in the air-breathing clown knifefish, Chitala ornata.

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 HCO3-/Cl- exchanger. Fish fitted with arterial catheters were exposed to normocapnic/normoxic water (control), nitrite (1 mM), hypercapnia (21 mmHg CO2), 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 [NO2-] + [NO3-]) 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 HCO3-/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.

A Quick Reference on Respiratory Acidosis.

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 Paco2, decreases in pH and compensatory increases in blood HCO3- concentration are associated with respiratory acidosis. Respiratory acidosis can be acute or chronic, with initial metabolic compensation to increase HCO3- concentrations by intracellular buffering. Chronic respiratory acidosis results in longer lasting increases in renal reabsorption of HCO3-. Alveolar hypoventilation and resulting respiratory acidosis may also be associated with hypoxemia, especially evident when patients are inspiring room air (20.9% O2).

Future ocean hypercapnia driven by anthropogenic amplification of the natural CO2 cycle.

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.