Cardiac output affects the response to pulsed inhaled nitric oxide in mechanically ventilated anesthetized ponies determined by CT angiography of the lung.

OBJECTIVE: To measure changes in regional lung perfusion using CT angiography in mechanically ventilated, anesthetized ponies administered pulsed inhaled nitric oxide (PiNO) during hypotension and normotension. ANIMALS: 6 ponies for anesthetic 1 and 5 ponies for anesthetic 2. PROCEDURES: Ponies were anesthetized on 2 separate occasions, mechanically ventilated, and placed in dorsal recumbency within the CT gantry. Pulmonary arterial, right atrial, and facial arterial catheters were placed. During both anesthetics, PiNO was delivered for 60 minutes and then discontinued. Anesthetic 1: hypotension (mean arterial pressure < 70 mmHg) was treated using dobutamine after 30 minutes of PiNO delivery. Following the discontinuation of PiNO, dobutamine administration was discontinued in 3 ponies and was continued in 3 ponies. The lung was imaged at 30, 60, and 105 minutes. Anesthetic 2: hypotension persisted throughout anesthesia. The lung was imaged at 30, 60, and 90 minutes. At all time points, arterial and mixed venous blood samples were analyzed and cardiac output (Q˙t) was measured. Pulmonary perfusion was calculated from CT image analysis. RESULTS: During PiNO delivery, perfusion to well-ventilated lungs increased if ponies were normotensive, leading to increased arterial oxygenation, reduced alveolar dead space, and reduced alveolar to arterial oxygen tension gradient. When PiNO was stopped and dobutamine administration continued, alveolar dead space and venous admixture increased, in contrast to when dobutamine and PiNO were both discontinued. CLINICAL RELEVANCE: If PiNO is administered to mechanically ventilated, anesthetized ponies with concurrent hypotension and low Q˙t, this must be supported to achieve favorable redistribution of pulmonary perfusion to improve pulmonary gas exchange.

Concentration of carprofen in the milk of lactating bitches after cesarean section and during inflammatory conditions.

Pain treatment of lactating bitches is a clinically relevant, but complicated issue. Published scientific studies regarding the excretion of drugs in canine milk are scarce. When considering the risk of side effects in their offspring, lactating bitches have traditionally received very restricted analgesic and anti-inflammatory therapy. Our aim was to quantify the concentrations of carprofen in milk from lactating bitches and relate those to potential risks for the puppies. A second aim was to evaluate the impact mastitis may have on the concentration of carprofen in milk. A population of 100 bitches was enrolled in the study, among which 88 were bitches treated with carprofen after cesarean section (Group CS), eight were bitches with painful inflammatory conditions (Group I) and four were bitches with mastitis (Group M). The patients enrolled in the study received carprofen 4 mg/kg sc at day 1 followed by 2 mg/kg po every 12 h for the following 2-5 days. Owners were instructed to collect milk once a day for five days. The concentration of carprofen in the milk was quantified with ultra-performance liquid chromatography-tandem mass spectrometry. The data obtained were statistically analyzed as repeated-measures data with a mixed-model approach. Data were used to calculate the theoretical maximum total daily intake of carprofen by the puppies in order to perform a computerized simulation of the plasma concentration of carprofen in the puppies. Follow-up telephone interviews to check the status of the enrolled bitches and their litters occurred at one week and three-six months after treatment with carprofen. The major finding of the study was that the concentration of carprofen in the milk was <700 ng/mL from bitches undergoing CS or suffering painful conditions other than mastitis. In comparison, administration of 2 mg/kg of carprofen sc or po to adult dogs, results in mean maximal plasma concentrations of 19480 ± 5420 ng/mL (mean ± SD). Moreover, data suggests that inflammation of the mammary gland results in a higher concentration of carprofen in milk (up to 1300 ng/mL). In the computerized simulation, the plasma concentrations of carprofen in puppies in group CS and in group I are one tenth of the concentration in adult dogs receiving carprofen at standard doses. Considering the low excretion into milk, carprofen provides an analgesic alternative to lactating bitches without mastitis.

Effects of pulsed inhaled nitric oxide delivery on the distribution of pulmonary perfusion in spontaneously breathing and mechanically ventilated anesthetized ponies.

OBJECTIVE: To measure changes in pulmonary perfusion during pulsed inhaled nitric oxide (PiNO) delivery in anesthetized, spontaneously breathing and mechanically ventilated ponies positioned in dorsal recumbency. ANIMALS: 6 adult ponies. PROCEDURES: Ponies were anesthetized, positioned in dorsal recumbency in a CT gantry, and allowed to breathe spontaneously. Pulmonary artery, right atrial, and facial artery catheters were placed. Analysis time points were baseline, after 30 minutes of PiNO, and 30 minutes after discontinuation of PiNO. At each time point, iodinated contrast medium was injected, and CT angiography was used to measure pulmonary perfusion. Thermodilution was used to measure cardiac output, and arterial and mixed venous blood samples were collected simultaneously and analyzed. Analyses were repeated while ponies were mechanically ventilated. RESULTS: During PiNO delivery, perfusion to aerated lung regions increased, perfusion to atelectatic lung regions decreased, arterial partial pressure of oxygen increased, and venous admixture and the alveolar-arterial difference in partial pressure of oxygen decreased. Changes in regional perfusion during PiNO delivery were more pronounced when ponies were spontaneously breathing than when they were mechanically ventilated. CLINICAL RELEVANCE: In anesthetized, dorsally recumbent ponies, PiNO delivery resulted in redistribution of pulmonary perfusion from dependent, atelectatic lung regions to nondependent aerated lung regions, leading to improvements in oxygenation. PiNO may offer a treatment option for impaired oxygenation induced by recumbency.

Development of a method to measure regional perfusion of the lung in anesthetized ponies using computed tomography angiography and the maximum slope model.

OBJECTIVE: To develop a method based on CT angiography and the maximum slope model (MSM) to measure regional lung perfusion in anesthetized ponies. ANIMALS: 6 ponies. PROCEDURES: Anesthetized ponies were positioned in dorsal recumbency in the CT gantry. Contrast was injected, and the lungs were imaged while ponies were breathing spontaneously and while they were mechanically ventilated. Two observers delineated regions of interest in aerated and atelectatic lung, and perfusion in those regions was calculated with the MSM. Measurements obtained with a computerized method were compared with manual measurements, and computerized measurements were compared with previously reported measurements obtained with microspheres. RESULTS: Perfusion measurements obtained with the MSM were similar to previously reported values obtained with the microsphere method. While ponies were spontaneously breathing, mean ± SD perfusion for aerated and atelectatic lung regions were 4.0 ± 1.9 and 5.0 ± 1.2 mL/min/g of lung tissue, respectively. During mechanical ventilation, values were 4.6 ± 1.2 and 2.7 ± 0.7 mL/min/g of lung tissue at end expiration and 4.1 ± 0.5 and 2.7 ± 0.6 mL/min/g of lung tissue at peak inspiration. Intraobserver agreement was acceptable, but interobserver agreement was lower. Computerized measurements compared well with manual measurements. CLINICAL RELEVANCE: Findings showed that CT angiography and the MSM could be used to measure regional lung perfusion in dorsally recumbent anesthetized ponies. Measurements are repeatable, suggesting that the method could be used to determine efficacy of therapeutic interventions to improve ventilation-perfusion matching and for other studies for which measurement of regional lung perfusion is necessary.

Correction: Rydén et al. Physiological and Clinical Responses in Pigs in Relation to Plasma Concentrations during Anesthesia with Dexmedetomidine, Tiletamine, Zolazepam, and Butorphanol. Animals 2021, 11, 1482.

Text Correction [...].

Comparison of two injectable anaesthetic techniques on induction and subsequent anaesthesia in pigs.

Pig experiments often require anaesthesia, and a rapid stress-free induction is desired. Induction drugs may alter the subsequent anaesthesia. Therefore, the aim of the present study was to compare, in pigs, the effects of two different injectable anaesthetic techniques on the induction and on the physiological variables in a subsequent eight hours of total intravenous anaesthesia (TIVA). Twelve domestic castrates (Swedish Landrace/Yorkshire) 27‒31 kg were used. The pigs were randomly assigned to different induction drug combinations of zolazepam-tiletamine and medetomidine intramuscularly (ZTMe) or midazolam, ketamine intramuscularly and fentanyl intravenously (MiKF). Time from injection to unconsciousness was recorded and the ease of endotracheal intubation assessed. The TIVA infusion rate was adjusted according to the response exhibited from the nociceptive stimulus delivered by mechanically clamping the dewclaw. The time from injection to unconsciousness was briefer and intubation was easier in the ZTMe group. Results from the recorded heart rate, cardiac index and arterial blood pressure variables were satisfactorily preserved and cardiovascular function was maintained in both groups. Shivering was not observed in the ZTMe group, but was observed in four of the pigs in the MiKF group. The requirement of TIVA was lower in the ZTMe group. In conclusion, ZTMe had better results than MiKF in areas such as shorter induction time, better intubation scoring results and less adjustment and amount of TIVA required up to six hours of anaesthesia. The results may have been due to a greater depth of anaesthesia achieved with the ZTMe combination at the dose used.

Physiological and Clinical Responses in Pigs in Relation to Plasma Concentrations during Anesthesia with Dexmedetomidine, Tiletamine, Zolazepam, and Butorphanol.

Reliable protocols for short-term anesthetics are essential to safeguard animal welfare during medical investigations. The aim of the study was to assess the adequacy and reliability of an anesthetic protocol and to evaluate physiological and clinical responses, in relation to the drug plasma concentrations, for pigs undergoing short-term anesthesia. A second aim was to see whether an intravenous dosage could prolong the anesthesia. The anesthesia was induced by an intramuscular injection of dexmedetomidine, tiletamine-zolazepam, and butorphanol in 12 pigs. In six of the pigs, a repeated injection intravenously of one-third of the initial dose was given after one hour. The physiological and clinical effects from induction to recovery were examined. Plasma concentrations of the drugs were analyzed and pharmacokinetic parameters were calculated. Each drug's absorption and time to maximal concentration were rapid. All pigs were able to maintain spontaneous respiration. The route of administration did not alter the half-life of the drug. The results suggest that intramuscular administration of the four-drug combination provides up to two hours of anesthesia with stable physiological parameters and an acceptable level of analgesia while maintaining spontaneous respiration. A repeated intravenous injection may be used to extend the time of anesthesia by 30 min.

Nursing and training of pigs used in renal transplantation studies.

The pig is commonly used in renal transplantation studies since the porcine kidney resembles the human kidney. To meet the requirements of intense caretaking and examination without stress, a 2-week socialisation and training programme was developed. Conventional cross-breed pigs (n = 36) with high health status were trained for 15 min/day in a four-step training programme before kidney transplantation. The systematic training resulted in calm animals, which allowed for ultrasound examination, blood sampling and urine sampling without restraint. When a 2-methacryloyloxyethyl phosphorylcholine polymer-coated jugular catheter introduced via the auricular vein was used for post-operative blood sampling, clotting was avoided. To assess renal function, urinary output was observed and creatinine and cystatin C were measured; the latter was not found to be useful in recently transplanted pigs. The results presented contribute to the 3Rs (refine, reduce, replace).

Evaluation and comparison of pain questionnaires for clinical screening of osteoarthritis in cats.

BACKGROUND: Feline osteoarthritis (OA) is a common cause of long-standing pain and physical dysfunction. Performing a physical examination of a cat is often challenging. There is a need for disease-specific questionnaires or the so-called clinical metrology instruments (CMIs) to facilitate diagnosis and evaluation of treatment of feline OA. The CMI provides the owners an assessment of the cat's behavioural and lifestyle changes in the home environment. The purpose of the study was to evaluate readability, internal consistency, reliability and discriminatory ability of four CMIs. METHODS: This is a prospective, cross-sectional study with 142 client-owned cats. Feline OA was diagnosed based on medical history, orthopaedic examination and radiography. RESULTS: The results indicate that all four instruments have sound readability, internal consistency, are reliable over time and have good discriminatory ability. Preliminary cut-off values with optimal sensitivity and specificity were suggested for each instrument. The osteoarthritic cats showed significant changes in behavioural response to pain during orthopaedic examination, compared with sound cats. CONCLUSION: The results indicate that all four questionnaires make an important contribution in a clinical setting, and that the cat's behavioural response to pain during physical examination should be a parameter to take into account as a possible indication of chronic pain.

Effects of ventilation mode and blood flow on arterial oxygenation during pulse-delivered inhaled nitric oxide in anesthetized horses.

OBJECTIVE To determine the impact of mechanical ventilation (MV) and perfusion conditions on the efficacy of pulse-delivered inhaled nitric oxide (PiNO) in anesthetized horses. ANIMALS 27 healthy adult horses. PROCEDURES Anesthetized horses were allocated into 4 groups: spontaneous breathing (SB) with low (< 70 mm Hg) mean arterial blood pressure (MAP; group SB-L; n = 7), SB with physiologically normal (≥ 70 mm Hg) MAP (group SB-N; 8), MV with low MAP (group MV-L; 6), and MV with physiologically normal MAP (group MV-N; 6). Dobutamine was used to maintain MAP > 70 mm Hg. Data were collected after a 60-minute equilibration period and at 15 and 30 minutes during PiNO administration. Variables included Pao2, arterial oxygen saturation and content, oxygen delivery, and physiologic dead space-to-tidal volume ratio. Data were analyzed with Shapiro-Wilk, Mann-Whitney U, and Friedman ANOVA tests. RESULTS Pao2, arterial oxygen saturation, arterial oxygen content, and oxygen delivery increased significantly with PiNO in the SB-L, SB-N, and MV-N groups; were significantly lower in group MV-L than in group MV-N; and were lower in MV-N than in both SB groups during PiNO. Physiologic dead space-to-tidal volume ratio was highest in the MV-L group. CONCLUSIONS AND CLINICAL RELEVANCE Pulmonary perfusion impacted PiNO efficacy during MV but not during SB. Use of PiNO failed to increase oxygenation in the MV-L group, likely because of profound ventilation-perfusion mismatching. During SB, PiNO improved oxygenation irrespective of the magnitude of blood flow, but hypoventilation and hypercarbia persisted. Use of PiNO was most effective in horses with adequate perfusion.

Pulsed inhaled nitric oxide improves arterial oxygenation in colic horses undergoing abdominal surgery.

OBJECTIVE: To evaluate the effect of pulsed inhaled nitric oxide (INO) on arterial oxygenation in horses during abdominal surgery. STUDY DESIGN: Prospective, randomized, clinical trial. ANIMALS: Thirty horses that underwent abdominal surgery at the University Animal Hospital in Uppsala, Sweden. METHODS: Anaesthesia was induced according to a standard protocol - romifidine, butorphanol, diazepam and ketamine and maintained with isoflurane in oxygen. Fifteen horses were administered pulsed INO and 15 served as controls. After baseline data collection, pulsed INO delivery commenced. Arterial and venous blood were collected and analysed. Cardiorespiratory parameters were measured, and oxygen content and F-shunt were calculated. RESULTS: Arterial oxygen tension (PaO2) and arterial oxygen saturation (SaO2) increased from 10.9±5.7 kPa (82±43 mmHg) and 93±6% to 17.3±6.9 kPa (134±52 mmHg) (p<0.0001) and 98±2% (p<0.0001), respectively, in horses administered pulsed INO. In the control group, PaO2 and SaO2 decreased from 13.9±9.1 kPa (104±68 mmHg) and 93±7% to 12.1±8.6 kPa (91±65 mmHg) (p=0.0413) and 91±8% (p=0.0256), respectively. At the end of anaesthesia, the oxygen content was significantly higher in horses administered pulsed INO compared to controls (p=0.0126). The calculated F-shunt decreased from 39±10% to 27±6% (p<0.0001) in horses administered pulsed INO, and remained unchanged in controls, 40±12% to 44±12%. Blood lactate concentration decreased (-17±21%) in horses administered pulsed INO (p=0.0119), whereas no difference was measured in controls (2±31%). CONCLUSIONS AND CLINICAL RELEVANCE: The present study showed that it is possible to effectively reduce the F-shunt and improve arterial oxygenation in horses during abdominal surgery by continuous delivery of pulsed INO.

Review of hypoxaemia in anaesthetized horses: predisposing factors, consequences and management.

OBJECTIVE: To discuss how hypoxaemia might be harmful and why horses are particularly predisposed to developing it, to review the strategies that are used to manage hypoxaemia in anaesthetized horses, and to describe how successful these strategies are and the adverse effects associated with them. DATABASES USED: Google Scholar and PubMed, using the search terms horse, pony, exercise, anaesthesia, hypoxaemia, oxygen, mortality, morbidity and ventilation perfusion mismatch. CONCLUSIONS: Although there is no evidence that hypoxaemia is associated with increased morbidity and mortality in anaesthetized horses, most anaesthetists would agree that it is important to recognise and prevent or treat it. Favourable anatomical and physiological adaptations of a horse for exercise adversely affect gas exchange once the animal is recumbent. Hypoxaemia is recognised more frequently in horses than in other domestic species during general anaesthesia, although its incidence in healthy horses remains unreported. Management of hypoxaemia in anaesthetized horses is challenging and often unsuccessful. Positive pressure ventilation strategies to address alveolar atelectasis in humans have been modified for implementation in recumbent anaesthetized horses, but are often accompanied by unpredictable and unacceptable cardiopulmonary adverse effects, and some strategies are difficult or impossible to achieve in adult horses. Furthermore, anticipated beneficial effects of these techniques are inconsistent. Increasing the inspired fraction of oxygen during anaesthesia is often unsuccessful since much of the impairment in gas exchange is a direct result of shunt. Alternative approaches to the problem involve manipulation of pulmonary blood away from atelectatic regions of the lung to better ventilated areas. However, further work is essential, with particular focus on survival associated with general anaesthesia in horses, before any technique can be accepted into widespread clinical use.

Case Studies in Physiology: Ventilation and perfusion in a giraffe-does size matter?

The trachea in the giraffe is long but narrow, and dead space ventilation is considered to be of approximately the same size as in other mammals. Less is known about the matching between ventilation and lung blood flow. The lungs in the giraffe are large, up to 1 m high and 0.7 m wide, and this may cause considerable ventilation/perfusion (VA/Q) mismatch due to the influence of gravitational forces, which could lead to hypoxemia. We studied a young giraffe under anesthesia using the multiple inert gas elimination technique to analyze the VA/Q distribution and arterial oxygenation and compared the results with those obtained in other species of different sizes, including humans. VA/Q distribution was broad but unimodal, and the shunt of blood flow through nonventilated lung regions was essentially absent, suggesting no lung collapse. The VA/Q match was as good as in the similarly sized horse and was even comparable to that in smaller sized animals, including rabbit and rat. The match was also similar to that in anesthetized humans. Arterial oxygenation was essentially similar in all studied species. The findings suggest that the efficiency of VA/Q matching is independent of lung size in the studied mammals that vary in weight from less than 1 to more than 400 kg.

Cardiovascular side-effects and insulin secretion after intravenous administration of radiolabeled Exendin-4 in pigs.

INTRODUCTION: Radiolabeled Exendin-4, a synthetic glucagon-like peptide-1 (GLP-1) analog, is used as a tracer for diagnostic purposes of ß-cells and in experimental animal research. Exendin-4 can be radiolabeled with (68)Ga, (111)In or (99m)Tc and used for positron emission tomography (PET) and single-photon emission computed tomography (SPECT) imaging to diagnose insulinomas, visualization of pancreatic ß-cell mass and transplanted Islets of Langerhans. In humans, Exendin-4 is widely used as a therapeutic agent for treatment of type 2 diabetes (T2D). The compound, which is administered subcutaneously (SC) may cause nausea, vomiting and a minor increase in the heart rate (HR). However, possible side-effects on cardiovascular functions after intravenous (IV) administration have not been reported. This study describes the Exendin-4 dose at which cardiovascular side-effects occur in pigs and cynomolgus monkeys. The IV effect of the tracer on insulin secretion is also investigated in pigs. METHODS: Seven clinically healthy littermate pigs (40days old) were used; three of them were made diabetic by streptozotocin (STZ). All pigs underwent PET imaging under general anesthesia to examine the glucagon-like peptide-1 receptor (GLP-1R) in ß-cells with radiolabeled Exendin-4. A baseline tracer dose IV [(68)Ga]Exendin-4 (0.025±0.010µg/kg) followed by a competition dose IV [(68)Ga]Exendin-4 (3.98±1.33µg/kg) 60min later were administered. Blood samples were taken and analyzed for insulin secretion by using ELISA. Cardiovascular and respiratory variables were monitored throughout the experiment. RESULTS: Immediately after administration of the high dose [(68)Ga]Exendin-4 the HR rose from 122±14 to 227±40bpm (p<0.01) and from 100±5 to 181±13bpm (p<0.01) in healthy non-diabetic and diabetes-induced pigs, respectively. The tachycardia was observed for >2h and one healthy non-diabetic pig suffered cardiac arrest 3h after the IV [(68)Ga]Exendin-4. Arrhythmia was detected by listening to the heart with a stethoscope up to 4days after the [(68)Ga]Exendin-4 injection. In all animals, no effect on the cardiovascular system was registered after the low dose of IV [(68)Ga]Exendin-4. Insulin secretion increased (p<0.05) when IV [(68)Ga]Exendin-4 was given in dosages ≥0.14µg/kg. CONCLUSIONS: Intravenous administration of ≥2.8µg/kg [(68)Ga]Exendin-4 resulted in severe tachycardia and arrhythmias in healthy non-diabetic and diabetes-induced pigs, and the insulin secretion was stimulated in healthy non-diabetic animals when ≥0.14µg/kg [(68)Ga]Exendin-4 was given.

Pulmonary gas exchange and acid-base status during immobilisation of black rhinoceroses (Diceros bicornis) in Zimbabwe.

When immobilising wildlife, adverse side effects can include hypoxaemia, acidosis and hypertension. Pulmonary gas exchange and acid-base status were evaluated during immobilisation of 25 free-ranging and one boma-held black rhinoceros (Diceros bicornis) in Zimbabwe. The effect of different body positions on arterial oxygenation was evaluated. A combination of the following drugs was used: an opioid (etorphine or thiafentanil), azaperone and an a2 -adrenoceptor agonist (detomidine or xylazine). Respiratory and heart rates, rectal temperature and pulse oximetry-derived haemoglobin oxygen saturation were recorded. Serial arterial blood samples were analysed immediately in the field. Marked hypoxaemia and hypercapnia were recorded in immobilised free-ranging black rhinoceroses. Arterial oxygenation was higher during sternal compared to lateral recumbency. Most rhinoceroses developed acidaemia of respiratory and metabolic origin. Initially high lactate concentrations in free-ranging rhinoceroses decreased during immobilisation. Pulse oximetry was unreliable in the detection of hypoxaemia. Positioning in sternal recumbency and routine use of oxygen supplementation are recommended in the management of immobilised rhinoceroses as measures to improve arterial oxygenation.

Effects of pulse-delivered inhaled nitric oxide administration on pulmonary perfusion and arterial oxygenation in dorsally recumbent isoflurane-anesthetized horses.

OBJECTIVE: To image the spatial distribution of pulmonary blood flow by means of scintigraphy, evaluate ventilation-perfusion (VA/Q) matching and pulmonary blood shunting (Qs/Qt) by means of the multiple inert gas elimination technique (MIGET), and measure arterial oxygenation and plasma endothelin-1 concentrations before, during, and after pulse-delivered inhaled nitric oxide (PiNO) administration to isoflurane-anesthetized horses in dorsal recumbency. ANIMALS: 3 healthy adult Standardbreds. PROCEDURES: Nitric oxide was pulsed into the inspired gases in dorsally recumbent isoflurane-anesthetized horses. Assessment of VA/Q matching, Qs/Qt, and Pao2 content was performed by use of the MIGET, and spatial distribution of pulmonary blood flow was measured by perfusion scintigraphy following IV injection of technetium Tc 99m-labeled macroaggregated human albumin before, during, and 30 minutes after cessation of PiNO administration. RESULTS: During PiNO administration, significant redistribution of blood flow from the dependent regions to the nondependent regions of the lungs was found and was reflected by improvements in VA/Q matching, decreases in Qs/Qt, and increases in Pao2 content, all of which reverted to baseline values at 30 minutes after PiNO administration. CONCLUSIONS AND CLINICAL RELEVANCE: Administration of PiNO in anesthetized dorsally recumbent horses resulted in redistribution of pulmonary blood flow from dependent atelectatic lung regions to nondependent aerated lung regions. Because hypoxemia is commonly the result of atelectasis in anesthetized dorsally recumbent horses, the addition of nitric oxide to inhaled gases could be used clinically to alleviate hypoxemia in horses during anesthesia.

Oxygen supplementation in anesthetized brown bears (Ursus arctos)-how low can you go?

Hypoxemia is anticipated during wildlife anesthesia and thus should be prevented. We evaluated the efficacy of low flow rates of supplemental oxygen for improvement of arterial oxygenation in anesthetized brown bears (Ursus arctos). The study included 32 free-ranging brown bears (yearlings, subadults, and adults; body mass 12-250 kg) that were darted with medetomidine-zolazepam-tiletamine (MZT) from a helicopter in Sweden. During anesthesia, oxygen was administered intranasally from portable oxygen cylinders at different flow rates (0.5-3 L/min). Arterial blood samples were collected before (pre-O2), during, and after oxygen therapy and immediately processed with a portable analyzer. Rectal temperature, respiratory rate, heart rate, and pulse oximetry-derived hemoglobin oxygen saturation were recorded. Intranasal oxygen supplementation at the evaluated flow rates significantly increased the partial pressure of arterial oxygen (PaO2) from pre-O2 values of 9.1 ± 1.3 (6.3-10.9) kPa to 20.4 ± 6.8 (11.1-38.7) kPa during oxygen therapy. When oxygen therapy was discontinued, the PaO2 decreased to values not significantly different from the pre-O2 values. In relation to the body mass of the bears, the following oxygen flow rates are recommended: 0.5 L/min to bears <51 kg, 1 L/min to bears 51-100 kg, 2 L/min to bears 101-200 kg, and 3 L/min to bears 201-250 kg. In conclusion, low flow rates of intranasal oxygen were sufficient to improve arterial oxygenation in brown bears anesthetized with MZT. Because hypoxemia quickly recurred when oxygen was discontinued, oxygen supplementation should be provided continuously throughout anesthesia.

Positron emission tomography imaging of the glucagon-like peptide-1 receptor in healthy and streptozotocin-induced diabetic pigs.

PURPOSE: The glucagon-like peptide-1 receptor (GLP-1R) has been proposed as a target for molecular imaging of beta cells. The feasibility of non-invasive imaging and quantification of GLP-1R in pancreas using the positron emission tomography (PET) tracer [(68)Ga]Ga-DO3A-VS-Cys(40)-Exendin-4 in non-diabetic and streptozotocin (STZ)-induced diabetic pigs treated with insulin was investigated. METHODS: Non-diabetic (n = 4) and STZ-induced diabetic pigs (n = 3) from the same litter were examined. Development of diabetes was confirmed by blood glucose values, clinical examinations and insulin staining of pancreatic sections post mortem. Tissue perfusion in the pancreas and kidneys was evaluated by [(15)O]water PET/computed tomography (CT) scans. The in vivo receptor specificity of [(68)Ga]Ga-DO3A-VS-Cys(40)-Exendin-4 was assessed by administration of either tracer alone or by competition with 3-6.5 µg/kg of Exendin-4. Volume of distribution and occupancy in the pancreas were quantified with a single tissue compartment model. RESULTS: [(15)O]water PET/CT examinations showed reduced perfusion in the pancreas and kidneys in diabetic pigs. [(68)Ga]Ga-DO3A-VS-Cys(40)-Exendin-4 uptake in the pancreas of both non-diabetic and diabetic pigs was almost completely abolished by co-injection of unlabeled Exendin-4 peptide. [(68)Ga]Ga-DO3A-VS-Cys(40)-Exendin-4 uptake did not differ between non-diabetic and diabetic pigs. In all animals, administration of the tracer resulted in an immediate increase in the heart rate (HR). CONCLUSION: Pancreatic uptake of [(68)Ga]Ga-DO3A-VS-Cys(40)-Exendin-4 was not reduced by destruction of beta cells in STZ-induced diabetic pigs.

The effects of pulse-delivered inhaled nitric oxide on arterial oxygenation, ventilation-perfusion distribution and plasma endothelin-1 concentration in laterally recumbent isoflurane-anaesthetized horses.

OBJECTIVES: Anaesthetized horses commonly become hypoxaemic due to ventilation/perfusion (V·A/Q·) mismatch and increased pulmonary shunt fraction (Qs·/Qt·). Pulse-delivered inhaled nitric oxide may improve oxygenation but may increase plasma concentration of the potent vasoconstrictor, endothelin-1 (ET-1). Objectives: Study 1) compare arterial oxygen concentration (PaO2) and saturation (SaO2), calculated Qs·/Qt· and ET-1 concentration; and Study 2) assess V·A/Q· matching and measured Qs·/Qt· in isoflurane-anaesthetized horses in left lateral recumbency receiving pulse-delivered inhaled nitric oxide (PiNO group) or inhalant gas only (C group). STUDY DESIGN: Prospective research trial. ANIMALS: Ten Healthy adult Standardbred horses. Two horses were anaesthestized in both groups in a random cross-over design with >4 weeks between studies. METHODS: Study 1) Cardiopulmonary data including PaO2, SaO2, Qs·/Qt· and ET-1 concentration were measured or calculated prior to and at various points during PiNO administration in 6PiNO and 6C horses. Two-way repeated measures anova with Bonferroni significant difference test was used for data analysis with p < 0.05 considered significant. Study 2) V·A/Q· matching and Qs·/Qt· were determined using the multiple inert gas elimination technique in 3 horses. Data were collected after 60 minutes of anaesthesia without PiNO (baseline) and 15 minutes after PiNO was pulsed during the first 30%, and then the first 60%, of inspiration. Data were descriptive only. RESULTS: Study 1) PaO2 and SaO2 were higher and calculated Qs·/Qt· was lower in the PiNO group than the C group at most time points. ET-1 was not different over time or between groups. Study 2) V·A/Q· matching and measured Qs·/Qt· were improved from baseline in all horses but PiNO60% provided no improvement when compared to PiNO30%. CONCLUSIONS AND CLINICAL RELEVANCE: PiNO delivered in the initial portion of the inspiration effectively relieves hypoxaemia in anaesthetized horses by improving V·A/Q· matching and decreasing Qs·/Qt· without affecting ET-1.