Effects of Equine Chorionic Gonadotropin on Ovulatory and Luteal Characteristics of Mares Submitted to an P4-Based Protocol of Ovulation Induction With hCG

The aim of this study was to evaluate the effect of equine chorionic gonadotropin (eCG) at the end of progesterone (P4) treatment on follicular and luteal characteristics during transition period (TP) and reproductive breeding season (RP). A total of 13 crossbred mares were distributed in two experimental groups in the spring and summer (n = 26). The animals received intravaginal P4 (1.9 g) releasing device from D0 to D10. On removal of P4 device, the mares received 400 IU of eCG (eCG group) or saline solution (control group). Human chorionic gonadotropin (hCG; 1.750 IU) was administered (DhCG) as soon as ovulatory follicle (OF) ≥35 mm was detected. Ovarian ultrasonography was performed from D0 until 15 days after ovulation. Blood samples were collected on D0, D5, D10, DhCG, 9 days after ovulation (CL9D), and 13 days after ovulation (CL13D). P4 and estradiol concentrations were assessed by chemiluminescence. Data were compared by Tukey test at P < .05. Ovulation rate was similar (P = .096) between seasons (RP = 100%; TP = 70%) but occurred earlier (P = .015) in RP (34.8 ± 10.1 hours) compared with TP (42.0 ± 10.4 hours). Interactions between season and treatment were observed for OF diameter (mm) (RP/control = 36.2 ± 1.8ab; RP/eCG = 32.9 ± 2.8 b; TP/control = 32.2 ± 1.2 b; TP/eCG = 37.2 ± 1.9a; P = .004) and for corpus luteum (CL) diameter (mm) on CL13D (RP/control = 25.4 ± 3.5a; RP/eCG = 22.5 ± 1.8ab; TP/control = 21.6 ± 4.9 b; TP/eCG = 27.4 ± 4.3a; P = .023), although no differences were observed for serum P4 on CL13D (RP/control = 6.0 ± 3.1 ng/mL; RP/eCG = 5.8 ± 0.9 ng/mL; TP/control = 3.6 ± 2.7 ng/mL; TP/eCG = 5.1 ± 2.3 ng/mL; P = .429) or for day of structural CL regression (RP/control = 12.8 ± 1.9; RP/eCG = 12.1 ± 1.1; TP/control = 11.0 ± 1.7; TP/eCG = 13.2 ± 2.0; P = .102). The application of eCG at the moment of P4 implant removal seemed to increase the capacity of luteal maintenance during spring TP. However, eCG treatment was worthless during the breeding season.     

Cardiac biomarker changes in camels (Camelus dromedarius) secondary to road transportation

ObjectivesLittle is known about cardiac biomarkers in camels despite their extensive use as draft animals. This study was designed to establish reference ranges for the cardiac biomarkers cardiac troponin I (cTnI) and creatine kinase myocardial b fraction (CK-MB) in healthy camels and to investigate their changes in response to road transportation.AnimalsTwenty-five healthy camels transported for a 5 h round-trip journey.MethodsNone of the camels had evidence of cardiac abnormalities on cardiac auscultation, echocardiography or electrocardiography. Three blood samples were obtained from each camel: 24 h before transportation (T0), within 2 h after unloading (T1) and 24 h after transportation (T2).ResultsThe mean cTnI concentration in the camels was 0.032 ± 0.023 ng/mL. All the camels had resting cTnI concentrations of <0.08 ng/mL. At T1, the cTnI concentration was significantly higher (P < 0.001) in all 25 camels compared to values at T0. The CK-MB concentration in the camels was 0.19 ± 0.05 ng/mL. All the camels had resting CK-MB concentrations of <0.33 ng/mL. At T1, the CK-MB concentration was higher in 3/25 camels compared to values at both T0 and T2. Concerning the hematobiochemical variables, significant increases were detected at T1 in total white blood cells, total protein, globulin, magnesium and phosphorus. Cardiac troponin I, CK-MB and all the hematobiochemical parameters had returned to their pre-transport values at T2.Conclusions5 h road transportation might have transient adverse effects on the cardiac muscle of healthy camels.     

Concentrations of platelet α2-adrenoceptors,lymphocyte muscarinic receptors,and blood monoamines in dogs (Canis familiaris) affected by canine cognitive dysfunction syndrome

Canine cognitive dysfunction syndrome (CDS) is a neurodegenerative disorder of aged dogs characterized by a progressive decline in cognitive function. In humans and laboratory animals, a variety of neurotransmitter abnormalities have been described in patients affected by age-related dementia. Specifically, the regulatory role of the catecholaminergic, serotonergic, and cholinergic systems has been outlined. The aim of the present study was to measure blood monoamine levels, platelet α₂-adrenergic receptors, and lymphocyte muscarinic receptors in healthy adult and aged dogs and in dogs affected by canine cognitive dysfunction. Based on clinical and behavioral examination, 40 dogs were divided into 3 groups: healthy adults (n = 14), aged dogs (n = 17), and aged dogs affected by canine cognitive dysfunction (n = 9). A significant reduction in plasma levels of norepinephrine and dopamine was observed both in aged dogs (0.16 ± 0.02 ng/mL, P < 0.01; 0.11 ± 02 ng/mL, P < 0.01, respectively) and in CDS dogs (0.14 ± 0.03 ng/mL, P < 0.05; 0.10 ± 00.005 ng/mL, P < 0.01, respectively) compared with adults (0.29 ± 0.04 ng/mL and 0.15 ± 0.02 ng/mL, respectively). No significant differences were observed among groups for α₂-adrenergic receptor concentrations. Canine lymphocytes express 2 distinct classes of muscarinic receptors, characterized by high (HA) and low affinity (LA) for [³H]-N-methyl-scopolamine. A significant age-dependent decrease in HA muscarinic receptors was observed. However, no differences were found between aged dogs (87.65 ± 11.08 sites/cell × 10²) and in CDS dogs (90.17 ± 6.75 sites/cell × 10² ) for HA muscarinic receptor concentrations. As far as LA muscarinic receptors are concerned, CDS dogs showed a significant increase (393.48 ± 63 sites/cell × 10²; P < 0.05) with respect to healthy adult dogs (188.84 ± 16.50 sites/cell × 10²). Our results suggest that the reduction in HA muscarinic receptor-binding sites could be representative of the physiological aging process, whereas the increase in lymphocyte LA muscarinic receptor levels could be related to the cognitive decline.     

Comparison of hydromorphone and butorphanol for management of pain in equine patients undergoing elective arthroscopy: a randomized clinical trial

ObjectiveTo compare the effects of hydromorphone and butorphanol in horses undergoing arthroscopy and describe the pharmacokinetics of hydromorphone in anesthetized horses.Study designRandomized controlled clinical trial.AnimalsA total of 40 adult horses admitted for elective arthroscopy.MethodsHorses were randomly assigned to be administered intravenous hydromorphone (0.04 mg kg^–1; group TxH; n = 19) or butorphanol (0.02 mg kg^–1; group TxB; n = 21) prior to surgery as part of a standardized anesthetic protocol. Pain was scored by two observers unaware of group assignment using the Equine Utrecht University Scale for Facial Assessment of Pain (EQUUS-FAP) and a composite pain scale (CPS) prior to surgery (baseline), 2 hours (P2) and 4 hours (P4) following recovery from anesthesia. Blood samples were collected at various time points for determination of plasma hydromorphone concentration using liquid chromatography–tandem mass spectrometry. Data were analyzed with a mixed-effect model.ResultsMedian (range) baseline EQUUS-FAP was 1.2 (0.0–4.0) with no effect of group, time points or interaction. Baseline CPS was similar between groups. Group TxH baseline CPS was 2.5 (0.0–10.0), increased at P2 [4.5 (0–10.0); p = 0.046] and returned to baseline values at P4 [3.0 (0.0–11.0)]. Group TxB baseline CPS was 2.0 (0.0–8.0), increased at P2 [3.5 (0.0–11.0); p = 0.009] and P4 [5.0 (0.0–11.0); p < 0.001]. Pharmacokinetic terminal half-life was 774 ± 82.3 minutes, area under the curve was 1362 ± 314 ng minutes mL^–1, clearance was 30.7 ± 7.23 mL minute^–1 kg^–1 and volume of distribution at steady state was 884 ± 740 mL kg^–1.ConclusionsHydromorphone, but not butorphanol, decreased CPS back to baseline at P4 after recovery.Clinical relevanceHydromorphone may provide superior postoperative analgesia compared with butorphanol in horses undergoing arthroscopy.     

Sexual maturity,seasonal estrus,and gestation in female Indo-Pacific bottlenose dolphins Tursiops aduncus inferred from serum reproductive hormones

Reproductive hormones in serum concentrations of progesterone, estradiol, and testosterone in female Indo-Pacific bottlenose dolphins (Tursiops aduncus, n = 12) housed in Ocean Park Hong Kong were investigated in the present study. Results showed that, onset of puberty of captive Indo-Pacific bottlenose dolphins was at 5 years while sexual maturity was at 6. Average serum progesterone concentrations in non-pregnant sexually mature individuals was 0.33 (0.25–0.97) ng/mL (interquartile), significantly higher than in immature ones 0.26 (0.25–0.38) ng/mL. This study found significant difference in serum estradiol concentrations between individuals at the onset of puberty (9.5 ± 1.7 pg/mL, ±SD) and not (below detection limit 9 pg/mL). A slightly seasonal breeding pattern, with progesterone values tend to be higher from February to October (0.38 [0.25–1.07] ng/mL) was inferred. During pregnancy, serum progesterone concentrations range from 10.54 ± 8.74 ng/mL (indexed month post-conception [IMPC] 0) to 25.49 ± 12.06 ng/mL (IMPC 2), and display a bimodal pattern with 2 peaks in early- (25.49 ± 12.06 ng/mL, IMPC 2) and late-pregnancy (21.71 ± 10.25 ng/mL, IMPC 12), respectively. Serum estradiol concentrations can seldom be detected in early-pregnancy and increase constantly in mid- (9.45 ± 1.83 pg/mL) and late-pregnancy (11.88 ± 3.81 pg/mL), with a spike (15.45 ± 6.78 pg/mL) 1 month prior to delivery. Serum testosterone concentrations elevate significantly in IMPC 7 (0.36 ± 0.10 ng/mL) compared to other months (0.16 ± 0.10 ng/mL) of the year. The present study provides normal concentration profiles for some reproductive hormones in female Indo-Pacific bottlenose dolphins and can contribute to the breeding monitoring of this species. Also, our study would shed further light on the reproductive physiology of small cetaceans.     

Pharmacokinetics and pharmacodynamics of hydromorphone after intravenous and intramuscular administration in horses

ObjectiveTo compare the pharmacokinetics and pharmacodynamics of hydromorphone in horses after intravenous (IV) and intramuscular (IM) administration.Study designRandomized, masked, crossover design.AnimalsA total of six adult horses weighing [mean ± standard deviation (SD))] 447 ± 61 kg.MethodsHorses were administered three treatments with a 7 day washout. Treatments were hydromorphone 0.04 mg kg^⁻1 IV with saline administered IM (H-IV), hydromorphone 0.04 mg kg^⁻1 IM with saline IV (H-IM), or saline IV and IM (P). Blood was collected for hydromorphone plasma concentration at multiple time points for 24 hours after treatments. Pharmacodynamic data were collected for 24 hours after treatments. Variables included thermal nociceptive threshold, heart rate (HR), respiratory frequency (f_R), rectal temperature, and fecal weight. Data were analyzed using mixed-effects linear models. A p value of less than 0.05 was considered statistically significant.ResultsThe mean ± SD hydromorphone terminal half-life (t_1/2), clearance and volume of distribution of H-IV were 19 ± 8 minutes, 79 ± 12.9 mL minute^⁻1 kg^⁻1 and 1125 ± 309 mL kg^⁻1. The t_1/2 was 26.7 ± 9.25 minutes for H-IM. Area under the curve was 518 ± 87.5 and 1128 ± 810 minute ng mL^⁻1 for H-IV and H-IM, respectively. The IM bioavailability was 217%. The overall thermal thresholds for both H-IV and H-IM were significantly greater than P (p < 0.0001 for both) and baseline (p = 0.006). There was no difference in thermal threshold between H-IV and H-IM. No difference was found in physical examination variables among groups or in comparison to baseline. Fecal weight was significantly less than P for H-IV and H-IM (p = 0.02).Conclusions and clinical relevanceIM hydromorphone has high bioavailability and provides a similar degree of antinociception to IV administration.IM hydromorphone in horses provides a similar degree and duration of antinociception to IV administration.     

Evaluation of an automatic approach device to the epidural space of Beagle dogs

ObjectiveTo compare the epidural anesthesia device (EPIA), which facilitates an automatic approach to location of the epidural space, with the performance of clinicians using tactile sensation and differences in pressure when inserting an epidural needle into the epidural space of a dog.Study designProspective, crossover experiment.AnimalsA total of 14 Beagle dogs weighing 7.5 ± 2.4 kg (mean ± standard deviation).MethodsEach dog was anesthetized three times at 2 week intervals for three anesthesiologists (two experienced, one novice) to perform 14 epidural injections (seven manual and EPIA device each). The sequence of methods was assigned randomly for each anesthesiologist. The dogs were anesthetized with medetomidine (10 μg kg^–1), alfaxalone (2 mg kg^–1) and isoflurane and positioned in sternal recumbency with the pelvic limbs extended cranially. Epidural puncture in the manual method was determined by pop sensation, hanging drop technique and reduced injection pressure, whereas using the device a sudden decrease in reaction force on the device was detected. A C-arm identified needle placement in the epidural space, and after administration of iohexol (0.3 mL), the needle length in the epidural space was defined as the mean value measured by three radiologists. Normality was tested using the Kolmogorov–Smirnov test, and significant differences between the two methods were analyzed using an independent sample t test.ResultsIn both methods, the success rates of epidural insertion were the same at 95.2%. The length of the needle in the epidural space using the device and manual methods was 1.59 ± 0.50 and 1.68 ± 0.88 mm, respectively, with no significant difference (p = 0.718).Conclusions and clinical relevanceEPIA device was comparable to human tactile sense for an epidural needle insertion in Beagle dogs. Further research should be conducted for application of the device in clinical environments.     

Comparison of the sedative effects of intranasal or intramuscular dexmedetomidine at low doses in healthy dogs: a randomized clinical trial

ObjectiveTo compare the sedative effects of dexmedetomidine administered either intranasally or intramuscularly to healthy dogs.Study designProspective, randomized, blinded, clinical trial.AnimalsA group of 16 client-owned healthy dogs.MethodsDogs were randomly allocated to one of two groups that were administered dexmedetomidine 5 μg kg^–1 via either the intranasal route (IN_Dex), through a mucosal atomization device in one nostril, or the intramuscular route (IM_Dex), into the epaxial muscles. Ease of intranasal administration, sedation score, onset of sedation, cardiopulmonary variables, mechanical nociceptive thresholds (MNTs) and response to venous catheterization were recorded at 0 (baseline), 5, 10, 15, 20, 25, 30, 35, 40 and 45 minutes, following drug administration. Data were compared with the one-way anova, Mann-Whitney U test, and chi-square test, where appropriate.ResultsGroups were not different for age, sex, weight, body condition score or temperament. Sedation scores, MNTs and response to intravenous catheter placement were not different when dexmedetomidine was administered by either route (p = 0.691; p = 0.630 and p = 0.435, respectively). Onset of sedation was not different between groups IN_Dex and IM_Dex reaching a score of 4.2 ± 0.9 and 5.5 ± 1.2 at 9 ± 5 and 8 ± 4 minutes, respectively (p = 0.467). The highest sedation score was achieved at 30 and 35 minutes and sedation scores were 9.7 ± 2.0 and 9.5 ± 2.3 in groups IN_Dex and IM_Dex, respectively (p = 0.799). Respiratory rate was higher in group IN_Dex (p = 0.014), while there were no differences between routes in heart rate (p = 0.275), systolic (p = 0.957), diastolic (p = 0.837) or mean arterial pressure (p = 0.921).Conclusions and clinical relevanceIntranasal administration of dexmedetomidine at 5 μg kg^–1 provides effective sedation in healthy dogs.     

Plasma kinetics,excretion in milk of eprinomectin,and its efficacy against Hypoderma spp. following topical administration in yaks

The plasma pharmacokinetics and mammary excretion of eprinomectin were determined in dairy yaks following topical administration at a dose of 0.5 mg/kg. The kinetics of plasma and milk concentrations were analyzed using a noncompartmental model. Plasma and milk concentrations of eprinomectin increased to reach maximal concentrations of 5.45 ± 2.84 and 2.29 ± 0.90 ng/mL at a T_max of 1.79 ± 0.57 and 2.00 ± 0.82 days, respectively. The concentration of eprinomectin in plasma was remained >0.5 ng/mL for more than 30 days after administration. The mean residence times of eprinomectin in plasma and milk were 14.73 ± 6.22 and 9.37 ± 2.81 days, respectively. The AUC value in plasma (55.89 ± 18.16 ng day/mL) was threefold greater than that in milk (18.02 ± 6.48 ng day/mL). The AUC milk/plasma ratio was 0.33 ± 0.08. The systemic availability of eprinomectin in yaks was lower than that observed value in other domestic bovines. The low level of eprinomectin excretion in milk suggests that eprinomectin can be used in yaks with zero milk‐withdrawal time. The efficacy of eprinomectin against naturally acquired larvae of Hypoderma spp. was also determined in yaks. Topically administrated eprinomectin at a dose of 0.5 mg/kg was 100% efficacious against larvae of Hypoderma bovis, H. lineatum, and H. sinense.     

Development of a severity scoring system for acute haemorrhage in anaesthetized domestic cats: the CABSS score

ObjectiveTo determine whether physiological, haematological, biochemical or electrolyte variables can predict severe haemorrhage in cats.Study designRandomized crossover study whereby each cat underwent mild and severe haemorrhage, with a 2 month period between events.AnimalsA group of six domestic cats aged 21 ± 1 months and weighing 4.9 ± 1.2 kg, mean ± standard deviation.MethodsCats were anaesthetized (buprenorphine, alfaxalone, isoflurane in oxygen at a fixed end-tidal concentration of 1.7%) before the haemorrhage event. In total, 34 variables were measured twice (prehaemorrhage and posthaemorrhage). The difference and percent change for each variable were compared between haemorrhage events (paired t test). Significant variables were placed into 13 different ratios (posthaemorrhage value of one variable divided by a posthaemorrhage value of a second variable) and compared (paired t test), and Cohen’s d (d) was calculated. Receiver operating characteristic curves were plotted and cut-off values for weak, moderate and strong indicators of severe haemorrhage were obtained.ResultsThe blood loss was 4.5 ± 1.1 mL kg^–1 and 26.8 ± 5.5 mL kg^–1 for mild and severe haemorrhage events, respectively. The most significant variables with large effect sizes were heart rate (HR), systolic arterial blood pressure (SAP), end-tidal carbon dioxide (Pe′CO₂), serum albumin, haematocrit and actual bicarbonate ion concentration [HCO₃⁻(act)]. The most robust ratios were: 1) shock index (d = –2.8; HR:SAP); 2) HR:Pe′CO₂ (d = –2.9); 3) serum albumin: haematocrit (d = 1.5); and 4) HR:HCO₃⁻(act) (d = –1.6). These ratios were included in the final proposed Cat Acute Bleeding Scoring System (CABSS).Conclusionsand clinical relevance Cats subjected to mild and severe haemorrhage demonstrated statistically and clinically relevant changes whereby four ratios could be created to make up the CABSS. The ratios detected and quantified the presence of severe haemorrhage in anaesthetized cats.     

Targeted fibre-optical intrabronchial lipopolysaccharide administration in pigs – a methodical refinement for improved accuracy in respiratory research

ObjectiveTo establish and evaluate a standardized method of targeted, intrabronchial drug delivery in pigs.Study designRandomized controlled trial.AnimalsA total of 16 German Landrace pigs (Sus scrofa), age range 12?16 weeks, and weighing 28?35 kg.MethodsThe animals were anaesthetized, intubated, and instrumented with extended cardiovascular monitoring. Lung injury was induced by administering via a flexible fibre-optic endoscope using 100 mL saline solution containing either 20 mg of Escherichia coli lipopolysaccharide (E. coli LPS) (n = 8) or no additive (sham, n = 8) into the two distal mainstem bronchi. The animals were monitored for 8 hours and arterial oxygenation, inspiratory pressure and arterial blood pressure were measured repeatedly. Post-mortem, lung tissue was prepared for histologic damage scoring and determination of proinflammatory cytokines Interleukin-6 (IL-6) and tumour necrosis factor alpha (TNFα). Statistical analyses were performed using inter-group analysis of variance and Student’s t tests. Data are presented as mean ± standard deviation. A p value <0.05 was considered significant.ResultsThe targeted application of LPS led to significant deterioration of oxygenation consistent with mild-to-moderate acute respiratory distress syndrome (ARDS) and hypotension (Horowitz ratio: sham 2 hour, 300 ± 39; LPS 2 hour, 193.7 ± 52; p < 0.001). Histologic analyses identified increased inflammation and oedema in the tissues of the animals in the LPS group IL-6 sham: 6.4 ± 4.4 × 10^–5 pg mL^–1; IL-6 LPS: 2.8 ± 2.4 × 10^–4 pg mL^–1, p = 0.015.ConclusionsThe targeted application of agents via flexible fibre-optic endoscopy is a valid, reliable method of causing controlled lung damage in a porcine model. The data presented suggest the feasibility and possible advantages of controlled application and could expand the array of techniques used to help understand the critical condition of ARDS. In addition, a targeted approach could help reduce animal numbers used for this purpose.     

Open approach to the ventral transversus abdominis plane in the dog: evaluation and injectate dispersion in cadavers

ObjectiveTo evaluate a direct intra-abdominal approach to injection of the ventral transversus abdominis plane (TAP) and compare the dispersion of two volumes of injectate.Study designProspective anatomic and feasibility study.AnimalsA total of 10 canine cadavers weighing 9 ± 4 kg.MethodsA ventral incision was made extending through the linea alba, from the umbilicus and extending 5 cm caudally. A single injection of an isovolumic mixture of iopamidol and new methylene blue was performed with a hypodermic needle placed within the TAP of each hemiabdomen, alternating between 0.5 mL kg^–1 in low-volume group (LV) and 1 mL kg^–1 in high-volume group (HV). Surgical staples marked the incision. Computed tomography and three-dimensional reconstruction of the tomographic images evaluated the dimensions, cranial and caudal spread beyond the incision and the total area of the injectate. Dissection determined the extent of nerve staining within the TAP adjacent to the abdominal incision. Wilcoxon signed rank (stain) or paired t test was used to compare variables between groups. Data are reported as mean ± standard deviation or median (range).ResultsInjectate spread was within the ventral TAP. Length of spread was 2.5 ± 1.6 cm greater in group HV than in group LV. There was a strong positive correlation between the surface area (p = 0.02, r = 0.71) and cranial–caudal spread of injectate (p = 0.041, r = 0.65) with volume.All but two LV injections were associated with staining of all nerves adjacent to the incision. Additional nerves caudal to the incision were stained in group HV (p = 0.02).ConclusionsThis approach to the TAP was easily performed, with volume of injectate positively influencing distribution.Clinical relevanceThis technique is easily applied and future prospective studies are warranted to determine its analgesic efficacy.     

Communications: Validation of a Solid-Phase Enzyme Immunoassay Technique for the Measure of Plasma Cortisol in Rainbow Trout

Abstract

A kit for a solid-phase enzyme immunoassay (SOPHEIA®) of cortisol in human sera was evaluated and validated for measuring cortisol in plasma of rainbow trout Oncorhynchus mykiss. The accuracy of the SOPHEIA was demonstrated by the recovery of exogenous cortisol concentrations of 25, 50, 100, and 250 ng/mL in charcoal-stripped fish plasma. The amounts (mean ± SE) recovered from triplicate samples were 29.9 ± 2.75, 47.5 ± 3.41, 101.7 ± 12.08, and 232.0 ± 11.06 ng/mL, respectively. The intra- and interassay coefficient of variation (CV = 100 × SD/mean) for cortisol levels in undisturbed fish (26.6 ± 1.18 ng/mL) were 14 and 10%, respectively. The intra- and interassay CV for elevated cortisol levels in stressed fish (330.8 ± 19.90 ng/mL) were 8 and 13%, respectively. Cross-reactivity determined for nine steroids in teleostean fish was negligible. Cortisol concentrations in serial dilutions of pooled fish plasma were parallel to the standard curve. Sensitivity (minimum detection limit) was 3.04 ng/mL. The SOPHEIA compared favorably to radioimmunoassay measurements of cortisol (r = 0.98; P < 0.001).     

Pharmacokinetics of tulathromycin in plasma and milk samples after a single subcutaneous injection in lactating goats (Capra hircus)

Eight adult female dairy goats received one subcutaneous administration of tulathromycin at a dosage of 2.5 mg/kg body weight. Blood and milk samples were assayed for tulathromycin and the common fragment of tulathromycin, respectively, using liquid chromatography/mass spectrometry. Pharmacokinetic disposition of tulathromycin was analyzed by a noncompartmental approach. Mean plasma pharmacokinetic parameters (±SD) following single‐dose administration of tulathromycin were as follows: C_max (121.54 ± 19.01 ng/mL); T_max (12 ± 12–24 h); area under the curve AUC_0→∞ (8324.54 ± 1706.56 ng·h/mL); terminal‐phase rate constant λz (0.01 ± 0.002 h⁻¹); and terminal‐phase rate constant half‐life t_1/2λz (67.20 h; harmonic). Mean milk pharmacokinetic parameters (±SD) following 45 days of sampling were as follows: C_max (1594 ± 379.23 ng/mL); T_max (12 ± 12–36 h); AUC_0→∞ (72,250.51 ± 18,909.57 ng·h/mL); λz (0.005 ± 0.001 h⁻¹); and t_1/2λz (155.28 h; harmonic). All goats had injection‐site reactions that diminished in size over time. The conclusions from this study were that tulathromycin residues are detectable in milk samples from adult goats for at least 45 days following subcutaneous administration, this therapeutic option should be reserved for cases where other treatment options have failed, and goat milk should be withheld from the human food chain for at least 45 days following tulathromycin administration.     

Effect of end-inspiratory pause on airway and physiological dead space in anesthetized horses

ObjectiveTo evaluate the impact of a 30% end-inspiratory pause (EIP) on alveolar tidal volume (V_Talv), airway (V_Daw) and physiological (V_Dphys) dead spaces in mechanically ventilated horses using volumetric capnography, and to evaluate the effect of EIP on carbon dioxide (CO₂) elimination per breath (Vco₂br^–1), PaCO_2, and the ratio of PaO₂-to-fractional inspired oxygen (PaO₂:FiO₂).Study designProspective research study.AnimalsA group of eight healthy research horses undergoing laparotomy.MethodsAnesthetized horses were mechanically ventilated as follows: 6 breaths minute^–1, tidal volume (V_T) 13 mL kg^–1, inspiratory-to-expiratory time ratio 1:2, positive end-expiratory pressure 5 cmH₂O and EIP 0%. Vco₂br^–1 and expired tidal volume (V_TE) of 10 consecutive breaths were recorded 30 minutes after induction, after adding 30% EIP and upon EIP removal to construct volumetric capnograms. A stabilization period of 15 minutes was allowed between phases. Data were analyzed using a mixed-effect linear model. Significance was set at p < 0.05.ResultsThe EIP decreased V_Daw from 6.6 (6.1–6.7) to 5.5 (5.3–6.1) mL kg^–1 (p < 0.001) and increased V_Talv from 7.7 ± 0.7 to 8.6 ± 0.6 mL kg^–1 (p = 0.002) without changing the V_TE. The V_Dphys to V_TE ratio decreased from 51.0% to 45.5% (p < 0.001) with EIP. The EIP also increased PaO₂:FiO₂ from 393.3 ± 160.7 to 450.5 ± 182.5 mmHg (52.5 ± 21.4 to 60.0 ± 24.3 kPa; p < 0.001) and Vco₂br^–1 from 0.49 (0.45–0.50) to 0.59 (0.45–0.61) mL kg^–1 (p = 0.008) without reducing PaCO₂.Conclusions and clinical relevanceThe EIP improved oxygenation and reduced V_Daw and V_Dphys, without reductions in PaCO₂. Future studies should evaluate the impact of different EIP in healthy and pathological equine populations under anesthesia.     

Pharmacokinetics and tissue disposition of meloxicam in beef calves after repeated oral administration

The objective of this study was to investigate the pharmacokinetics and tissue disposition of meloxicam after repeated oral administration in calves. Thirteen male British × Continental beef calves aged 4 to 6 months and weighing 297–392 kg received 0.5 mg/kg meloxicam per os once daily for 4 days. Plasma meloxicam concentrations were determined in 8 calves over 6 days after first treatment. Calves were randomly assigned to be euthanized at 5, 10, 15 (n = 3/timepoint), and 19 days (n = 4) after final administration. Meloxicam concentrations were determined in plasma (LOQ= 0.025 μg/mL) and muscle, liver, kidney, and fat samples (LOQ = 2 ng/g) after extraction using validated LC–MS–MS methods. The mean (± SD) C_max, C_min, and C_average plasma meloxicam concentrations were 4.52 ± 0.87 μg/mL, 2.95 ± 0.77 μg/mL, and 3.84 ± 0.81 μg/mL, respectively. Mean (± SD) tissue meloxicam concentrations were highest in liver (226.67 ± 118.16 ng/g) and kidney samples (52.73 ± 39.01 ng/g) at 5 days after final treatment. Meloxicam concentrations were below the LOQ in all tissues at 15 days after treatment. These findings suggest that tissue from meloxicam‐treated calves will have low residue concentrations by 21 days after repeated oral administration.     

Efficacy of the Parasympathetic Tone Activity monitor to assess nociception in healthy dogs anaesthetized with propofol and sevoflurane

ObjectiveTo compare a Parasympathetic Tone Activity (PTA) monitor with cardiovascular changes in invasive mean arterial pressure (IMAP) and heart rate (HR) when evaluating the response to nociceptive stimuli in anaesthetized dogs.Study designProspective experimental study.AnimalsA group of nine (seven male and two female) adult Beagle dogs weighing 13.4 ± 1.5 kg (mean ± standard deviation).MethodsAnaesthesia was induced with propofol and maintained with sevoflurane in oxygen. Electrical stimuli of different nociceptive intensities were applied for 30 seconds. Stimuli were classified in each patient according to the response obtained (relevant change ≥ 20%) as low (no response), medium (PTA only) or high (PTA and IMAP/HR). Immediate and averaged values of PTA, IMAP and HR were recorded every second from 60 seconds before to 120 seconds after application of the nociceptive stimulus. Time to nociceptive response and peak response were evaluated with analysis of variance and t test.ResultsImmediate PTA baseline values did not differ significantly before application of the low, medium and high stimuli (73 ± 15, p = 0.966). Immediate PTA response was observed with the medium stimulus at 33 ± 7 seconds with a maximum decrease of 57 ± 13% at 69 ± 5 seconds. With the high stimulus, the immediate PTA response was of a similar magnitude to the medium stimulus with a response at 28 ± 7 seconds (p = 0.221) and a maximum decrease of 68 ± 15% (p = 0.115) at 72 ± 7 seconds (p = 0.436). The cardiovascular change occurred (22 ± 8 seconds) prior to the immediate PTA response (p = 0.032).Conclusions and clinical relevanceThe PTA monitor detected nociceptive stimuli at lower intensities than those eliciting cardiovascular changes. However, nociceptive stimuli of higher intensities provoked cardiovascular changes that occurred before a PTA response was observed.