Pharmacokinetics and pharmacodynamics of intravenous dexmedetomidine (2 µg∙kg-1) in dogs.

This study assessed the pharmacokinetics and pharmacodynamics of low-dose dexmedetomidine after IV bolus in dogs. Six healthy adult dogs (6.8 ± 3.0 kg) received dexmedetomidine (2 µg.kg-1 IV) over 2 min, using an infusion pump. Blood samples were collected totaling 5 h of monitoring. A validated UHPLC-MS/MS method was used to determine the plasma concentration of dexemedetomidine. For pharmacodynamics, HR, RR, oscillometric MBP, Grint END sedation score were evaluated at baseline (T0), every 3 min (T3 to T21), and after 30 (T30) and 60 (T60) minutes, with p < 0.05. T1/2 was 28.28 ± 6.14 min; the area under the curve was 467.44 ± 60.42 ng/mL/min. The total clearance was 5.46 ± 0.41 mL/min/kg, the Vdss was 146.19 ± 21.04 mL/kg, and the C max was 3.13 ± 1.15 ng/mL. HR (bpm) decreased significantly from T6 (79 ± 21) to T21 (78 ± 31) compared to T0 (116 ± 28). RR(mpm) decreased from T3 (43 ± 44) to T60 (41 ± 23), with T0 being 70 ± 48. The MBP (mmHg) increased at T18 (151 ± 34), T21 (152 ± 35), and T30 (140 ± 27), compared to T0 (111 ± 22). Sedation occurred at all times post-bolus, with a maximum peak at T12 (END 8 ± 6). The low dose of dexmedetomidine provided sedation in all animals, characterizing rapid metabolization and elimination. However, cardiovascular effects still may have negative repercussions in dogs with hemodynamic comorbidities, highlighting the caution and individualization of its use in certain patients.

Pharmacotherapeutic monitoring of dipyrone in northeastern Brazilian donkeys (Equus asinus).

This study aimed to monitor the effects of dipyrone following multiple administrations in northeastern donkeys. Ten castrated male donkeys, aged 6.4 ± 3 years and weighing 130.6 ± 9.8 kg, were administered dipyrone (25 mg/kg IV) every 12 h, resulting in six administrations (D1 to D6) per animal. Blood samples were collected over a 72 h monitoring period. A validated UHPLC-MS/MS method was employed to determine the plasma concentrations of the 4- methylaminoantipyrine (4-MAA) and 4-aminoantipyrine (4-AA). The calculated pharmacokinetic variables of 4-MAA after D1 and D6 were, respectively: Cmax (µg/mL) = 163.60 ± 179.72 and 178.79 ± 196.94; T1/2beta (h) = 2.65 ± 0.65 and 3.37 ± 1.03; and AUC0-t (µg/mL × h) = 240.38 ± 130.87 and 373.52 ± 78.85. The same variables for 4-AA were: Cmax, (µg/mL) = 0.44 ± 0.27 and 0.90 ± 0.31, T1/2beta (h) = 14.77 ± 13.13 and 35.97 and AUC0-t (µg/mL × h) = 3.20 ± 0.43 and 27.73 ± 11.99. Concentrations of 4-MAA exceeded the minimum concentration required for 50% inhibition of cyclooxygenases 1 and 2. However, an accumulation of 4-AA, was observed. Further clinical studies are necessary to ascertain the implications of these findings on the pharmacodynamic response to dipyrone in northeastern donkeys.

Abdominal aortic branches of red-rumped agouti (Dasyprocta leporina Linnaeus, 1758).

Understanding the cardiovascular system is fundamental in diagnosing pathologies and interpreting exams, such as contrast radiographs. In this context, the present study describes the collateral abdominal aorta artery branches of red-rumped agouti. Ten red-rumped agoutis, six males and four females, were assessed. The vascular system was perfused with Neoprene 450 latex coloured with a yellow pigment, dissected and analysed. Three euthanized animals were perfused with a barium sulfate solution (1 g mL-1 ) associated with latex Neoprene 450 at a 1:3 ratio to obtain contrast-enhanced radiographs. The abdominal aorta emitted the celiac artery, which in turn originated the left gastric, hepatic and splenic arteries. The second collateral branch comprised the cranial mesenteric artery, followed by the renal arteries, which emitted the adrenal arteries, with the caudal emergence of the gonadal arteries. The caudal mesenteric artery appeared in a caudal direction. The abdominal aorta divided after reaching the pelvic cavity entrance, originating the right and left common iliac arteries. Before its bifurcation, the abdominal aorta dorsocaudally emitted its last collateral branch, the median sacral artery. The collateral branches of the aorta, therefore, resemble previously described rodent patterns, with few variations.

Pharmacokinetic profiles of the two major active metabolites of metamizole, 4-methylaminoantipyrine (MAA) and 4-aminoantipyrine (AA), after intravenous injection in cats.

This study aimed to determine the pharmacokinetic profile of two active metabolites of metamizole (dipyrone), N-methyl-4-aminoanthypyrine (MAA) and 4-aminoanthypyrine (AA), after intravenous administration in cats. Eight healthy mixed-breed cats were intravenously administered metamizole (25 mg/kg). Blood samples were collected at predetermined time points for up to 48 h after administration. Information on behavioral changes in the animals and adverse effects was collected. Plasma aliquots were processed and analyzed using the ultra-performance liquid chromatography tandem mass spectrometry technique. A validated UPLC-MS/MS method was used to characterize the pharmacokinetics of MAA and AA. Salivation was identified as an adverse clinical sign. The mean maximal plasma concentrations of MAA and AA were 29.31 ± 24.57 µg/mL and 1.69 ± 0.36 µg/mL, with half-lives of around 4.98 and 14 h, respectively. The area under the plasma concentration curve values were 28.54 ± 11.33 and 49.54 ± 11.38 h*µg/mL for MAA and AA, respectively. The plasma concentration of MAA was detectable for up to 24 h and was smaller than AA. AA was detectable for >48 h. Results suggest that metamizole is converted into active metabolites in cats. Further PK/PD and safety studies should be performed before defining the dose or administration intervals for clinical use.

Validation of the Donkey Pain Scale (DOPS) for Assessing Postoperative Pain in Donkeys.

This study aimed to validate a scale for assessing acute pain in donkeys. Forty-four adult donkeys underwent castration after sedation with intravenous (IV) xylazine, induction with guaifenesin and thiopental IV, local anesthetic block, and maintenance with isoflurane. The scale was constructed from a pilot study with four animals combined with algetic behaviors described for equines. After content validation, the scale was evaluated in 40 other donkeys by three blinded and one reference evaluator, by means of edited videos referring to the preoperative and postoperative periods: before anesthesia, 3-4 h after recovery from anesthesia, 5-6 h after recovery from anesthesia (2 h after analgesia with flunixin-1.1 mg/kg, dipyrone-10 mg/kg, and morphine-0.2 mg/kg) IV, and 24 h after recovery. Content validity, sensitivity, specificity, and responsiveness of behaviors were investigated to refine the scale. Intra- and inter-evaluator reliabilities were investigated by the weighted kappa coefficient, criterion validity by comparing the scale with the visual analog scale (VAS), internal consistency by Cronbach's α coefficient, item-total correlation by the Spearman coefficient, and intervention point for rescue analgesic by the receiver operating characteristics curve and Youden index. The scale showed very good intra-evaluator reliability (0.88-0.96), good to moderate (0.56-0.66) inter-evaluator reliability, responsiveness for all items, good criterion validity vs. VAS (0.75), acceptable internal consistency (0.64), adequate item-total correlation, except for head position and direction, and according to the principal component analysis, good association among items. The accuracy of the point for rescue analgesic was excellent (area under the curve = 0.91). The rescue analgesic score was ≥ 4 of 11 points. The scale can diagnose and quantify acute pain in donkeys submitted to castration, as the instrument is reliable and valid, with a defined intervention analgesic score.

Post-operative pain behaviour associated with surgical castration in donkeys (Equus asinus).

BACKGROUND: Recognising pain in donkeys is challenging because they are stoic. OBJECTIVES: To identify the responses of donkeys before and after surgical pain. STUDY DESIGN: Prospective, short-term longitudinal pre- and post-intervention observations. METHODS: Forty adult donkeys underwent surgical castration after sedation with intravenous (IV) xylazine, induction with guaiphenesin/thiopental IV and maintenance of anaesthesia with isoflurane and local anaesthetic blockade. Four hours after recovery from anaesthesia, flunixin meglumine 1.1 mg/kg, dipyrone 10 mg/kg and morphine 0.2 mg/kg IV were administered. Behavioural responses exhibited by the animals housed in individual stalls were recorded in four 30-min videos: before castration (M0), and 3.5-4.0 hours (M1), 5.5-6.0 hours (M2) and 23.5-24.0 hours after recovery from anaesthesia (M3). To exclude the influence of insects, the behaviour of six apparently pain-free donkeys was compared with and without the presence of faeces and urine in the stall. RESULTS: When compared with presurgical baseline behaviours (M0), after surgery (M1) donkeys raised their pelvic limbs more (P = .003). When compared with M1, after analgesia (M2), the median frequencies of ear movements (44 vs 16; P < .001), head shaking (7 vs 1; P < .001), head turning (5 vs 0; P < .001) and lifting of the both limbs (7 vs 0; P = .008) decreased; feeding (0 vs 29; P < .001) and water intake (0 vs 0, range 0-1 vs 0-7; P = .05) increased. The dirty stall increased tail (53 vs 80; P = .03), head (16 vs 30; P = .03) and ear movements (50 vs 78; P = .04). MAIN LIMITATIONS: The dirty stall and presence of insects possibly contributed to the expression of behaviours unrelated to pain. CONCLUSION: Lifting the pelvic limbs was the only specific pain behaviour after castration in donkeys. Analgesia restored appetite and water intake and reduced the frequency of head shaking and turning, ear movement and lifting the limbs. Tail, head and ear movements are unspecific responses related both to pain and a dirty stall, and are confounding factors when pain is assessed in donkeys in the presence of insects.

Pharmacokinetic properties of tramadol and M1 metabolite in Northeast Brazilian donkeys (Equus asinus).

There is currently little information available on the pharmacokinetics and pharmacodynamics of the analgesic opioid tramadol when used in the veterinary medicine of domestic species. In this study, we aimed to determine the pharmacokinetics of tramadol and its active metabolite M1 following intravenous administration of 2 (T2) and 4 (T4) mg/kg to Northeast Brazilian donkeys. Tramadol and M1 plasma levels were quantified using a validated liquid chromatography-tandem mass spectrometry method. We found that plasma levels of tramadol and M1 were higher than those reported as clinically meaningful in humans for at least 3 hr. However, the pharmacokinetic parameter calculation corrected by dose analysis identified no proportional increase with dose for the AUC of tramadol (T2: 2,663 ± 1,827 vs. T4: 2,964 ± 1,038 ng*h/ml) and M1 (T2: 378 ± 237 vs. T4: 345 ± 142 ng*h/ml). This finding appears to be attributable to a significant increase in clearance and a reduction in the terminal half-life of tramadol. The frequency of adverse effects observed at the higher dose indicates that 2 mg/kg administered intravenously would be suitable for donkeys. Clinical studies are required to determine the implications of these observations regarding the pharmacodynamic response to tramadol in Northeast Brazilian donkeys.

Are locally adapted goats able to recover homeothermy, acid-base and electrolyte equilibrium in a semi-arid region?

The objective of this study was to evaluate the thermoregulatory responses, acid-basic and electrolytic equilibrium of locally adapted goats under natural heat conditions in a semi-arid region. Ten (10) Canindé goats aged between 2 and 3 years, non-lactating, non-pregnant and having a body weight (BW) of 22.90 ± 2.70 kg were used in this study. Air temperature (AT) and relative humidity (RH) were measured, and the radiant heat load (RHL) was subsequently calculated. Rectal temperature (RT), respiratory rate (RR), sweating rate (SR) and heat shock (S) were recorded at 1-h intervals for 24 continuous hours. Hydrogen potential (pH), partial pressure of carbon dioxide (PCO2), partial pressure of oxygen (PO2), bicarbonate (HCO3), base excess (BE), total carbon dioxide concentration (TCO2), oxygen saturation (SO2), sodium (Na+) and potassium (K+) were recorded at three moments during the day (5 a.m.; 1 p.m.; 6 p.m.). There were also significant differences between the means of hours of the day for AT and RH. RR was the thermoregulatory response which most closely followed RHL, with important elevations in the periods between 10 a.m. to noon. It was observed that the goats activated their SR mechanism before RR, more precisely between the hours of 9 a.m. and 1 p.m. The acid-base and electrolytic equilibrium for the goats which showed great association with the first components contributed the most to the total variation of the data. The most important variables in the adaptive profile of these animals in order of importance were: SO2, PO2, RR, RT, SR, HCO3, BE, TCO2 and pH. An association between all variables grouped in each period was observed, where the thermoregulatory responses in the periods of 5 a.m. and 6 p.m. were closer than when compared to 1 p.m., showing a physiological return to the initial state. Therefore, the variation in thermoregulatory responses, acid-base and electrolytic equilibrium indicated that the goats have the ability to recover after a challenging environmental condition.

Sperm characteristics following freezing in extenders supplemented with whole egg yolk and different concentrations of low-density lipoproteins in the collared peccary (Pecari tajacu).

The aim of the current study was to compare sperm quality characteristics of the collared peccary (Pecari tajacu) following freezing in extenders supplemented with whole egg yolk and different concentrations of low-density lipoproteins (LDL). Semen from 11 adult males was obtained by electroejaculation and evaluated for sperm motility, vigor, morphology as well as membrane integrity analyzed by the hypo-osmotic swelling (HOS) test and a fluorescent staining. Moreover, the semen was diluted in a Tris-based extender containing 20% egg yolk (control group) or 5, 10 or 20% LDL (treatment groups). The semen samples were frozen in liquid nitrogen and thawed in a water bath for 60s at 37°C. The treatments did not affect (p>0.05) sperm vigor, morphology or membrane integrity analyzed by the HOS test. However, post-thaw sperm motility was significantly higher (p<0.05) in the extender supplemented with 20% LDL (36.4 ± 5.3%) compared with the egg yolk extender and extender supplemented with 10% LDL. Furthermore, the percentage of membrane-intact frozen-thawed spermatozoa analyzed by the fluorescent staining was significantly higher (p<0.05) in the extender supplemented with 20% LDL (27.4 ± 6.5%) than in the other groups. In conclusion, 20% LDL can be used to substitute the whole egg yolk as a cryoprotective additive for freezing semen of the collared peccary.

Microscopy of the umbilical cord of rock cavies--Kerodon rupestris Wied, 1820 (Rodenta, Caviidae).

The rock cavies (Kerodon rupestris) are rodents belonging to family Caviidae, with habitat restricted to northeastern Brazil. Current studies have shown that blood cord has stem and hematopoietic cells both with a high regenerative potential, microscopic studies about the description in rodents and other mammals are scarce. The aim of this study was to describe the structural components of the umbilical cord of rock cavies. Rock cavies embryos at different stages of pregnancy were used, three in the first third, five in middle third, and six in the final third of gestation. They were obtained at the Centre for Wild Animals Multiplication of Federal Rural University of Semi-Arid. In rock cavies was observed that the number of vessels involved in the transport of maternal substances was represented by two major arteries, veins and an allantois duct. The umbilical cord was delimited by amniotic epithelium, formed by a layer of squamous cells, connective tissue with characteristic of the mucosal tissue, corresponding to the Wharton jelly (fetal mesenchyme), where elastic fibers were observed and intercellular spaces were arranged in concentric blades. The morphology observed in rock cavies is similar to that described in the literature for other mammals, including man. The rock cavies are well adapted to captivity and are docile, which makes this animal an important model for study within the field of regenerative medicine. The knowledge of the umbilical cord morphology represents a base point for using this animal as a model for culture and cell therapy.