The Effect of Reversible Left Recurrent Laryngeal Neuropathy on the Metabolic Cost of Locomotion and Peak Aerobic Power in Thoroughbred Racehorses

W. ROBERT COOK, BVSc, FRCVS The effect of left recurrent laryngeal neuropathy (LRLN) on the metabolic cost of locomotion (MCL) and peak aerobic power (V?O₂peak) was evaluated in four trained Thoroughbred racehorses. Oxygen consumption (V?O₂), carbon dioxide production (V?CO₂), venous lactate concentrations (LAC), and heart rate (HR) were measured during a treadmill exercise test (TET). Each horse performed the exercise test four times, alternating between normal upper airway function and reversibly induced LRLN. Subcutaneous infusion of 2% mepivicaine, a local anesthetic, into the region where the left recurrent laryngeal nerve passes caudal to the cricoid cartilage was used to induce LRLN. The induction of LRLN did not alter the relationship between V?O₂ and treadmill speed at exercise intensities where V?O₂ was less than V?O₂peak (<9 m/sec). However, a 15.3% reduction in V?O₂peak (Normal = 165.3 ± 3.4, LRLN = 140.0 ± 3.2 mL/kg/min ± SE, P <.001) occurred at higher treadmill speeds in horses with induced LRLN. A significant group (Normal v LRLN) by treadmill speed effect was found for LAC and R only at treadmill speeds where V?O₂=V?O₂peak. Peak lactate (LACpeak) did not change after the induction of LRLN. The relationship between HR and treadmill speed increased in horses with induced LRLN at exercise intensities where V?O₂ < V?O₂peak. Peak heart rate (HRpeak) remained unchanged. Performance as indicated by the maximum number of speed intervals completed (STEPmax) decreased 7% in horses with induced LRLN (Normal = 9.1 ± 0.04, LRLN = 8.5 ± 0.2 minutes ± SE, P <.04). A comparison of paired exercise test measurements showed no evidence of a training effect, or decreased performance caused by a learned response, over the course of the experiment. The results of this study indicate that alterations in ventilation caused by LRLN cause a significant reduction in V?O₂peak, but do not cause an increase in the metabolic cost of locomotion at exercise intensities where V?O₂ is less than V?O₂peak.     

Pharmacokinetics and toxicity of ciprofloxacin in adult horses

Yamarik, T. A., Wilson, W. D., Wiebe, V. J., Pusterla, N., Edman, J., Papich, M. G. Pharmacokinetics and toxicity of ciprofloxacin in adult horses. J. vet. Pharmacol. Therap. 33 , 587–594. Using a randomized, cross‐over study design, ciprofloxacin was administered i.g. to eight adult mares at a dose of 20 mg/kg, and to seven of the eight horses at a dose of 5 mg/kg by bolus i.v. injection. The mean C₀ was 20.5 μg/mL (±8.8) immediately after i.v. administration. The C_max was 0.6 μg/mL (±0.36) at T_max 1.46 (±0.66) h after the administration of oral ciprofloxacin. The mean elimination half‐life after i.v. administration was 5.8 (±1.6) h, and after oral administration the terminal half‐life was 3.6 (±1.7) h. The overall mean systemic availability of the oral dose was 10.5 (±2.8)%. Transient adverse effects of mild to moderate severity included agitation, excitement and muscle fasciculation, followed by lethargy, cutaneous edema and loss of appetite developed in all seven horses after i.v. administration. All seven horses developed mild transient diarrhea at 36–48 after i.v. dosing. All eight horses dosed intragastrically experienced adverse events attributable to ciprofloxacin administration. Adverse events included mild transient diarrhea to severe colitis, endotoxemia and laminitis necessitating euthanasia of three horses on humane grounds. The high incidences of adverse events preclude oral and rapid i.v. push administration of ciprofloxacin.     

Platelet‐Activating Factor and Evidence of Oxidative Stress in the Bronchoalveolar Fluid of Thoroughbred Colts during Race Training

Background: Inflammatory airway disease (IAD) is prevalent in young racehorses during training, being the 2nd most commonly diagnosed ailment interrupting training of 2‐year‐old Thoroughbred racehorses. Hypothesis: That stabling and exercise cause oxidative stress, release of platelet‐activating factor (PAF) and inflammation in airways of Thoroughbred colts. Animals: Colts in breeding farms (NC, n = 45), stabled for 30 days (EC, n = 40), and race trained (EX, n = 34). Methods: Cytological profile and parameters of bronchoalveolar lavage fluid (BALF) related to oxidative stress, bioactivity of the proinflammatory mediator PAF, catalase activity, and alveolar macrophage function. Results: Percentages of neutrophils and eosinophils in the BALF of the EX group were higher (5.4 ± 6.4% versus 0.9 ± 1.2%) than the upper limits for normal horses (3–5%). BALF from the EX group (45.6 ± 2.8 cells/μL of BALF) also displayed significantly (P= .017) higher total nucleated cell count. PAF bioactivity and the total protein concentration in the BALF were higher in the EX group (0.0683 ± 0.076 versus 0.0056 ± 0.007 340 : 380 nm ratio P= .0039, 0.36 ± 0.30 versus 0.14 ± 0.15 mg of proteins/mL of BALF P < .001). Concentration of BALF hydroperoxides was higher in the EC group (104.7 ± 80.0 versus 35.2 ± 28.0 nmol/mg of proteins, P= .013) and catalase activity was higher in the EX group (0.24 ± 0.16 versus 0.06 ± 0.02 μmol H₂O₂/min/mg of proteins, P= .0021). Alveolar macrophage phagocytosis (P= .048) as well as production of superoxide anion (P= .0014) and hydrogen peroxide (P= .0011) were significantly lower in EX group. Conclusions and Clinical Importance: Further studies should be performed to elucidate the role of PAF in the pathophysiology of IAD. Its presence in bronchoalveolar fluid of young athletic horses makes it a potential therapeutic target to be investigated.     

Effects of clopidogrel and aspirin on platelet aggregation, thromboxane production, and serotonin secretion in horses

Background: Critically ill horses are susceptible to thrombotic disease, which might be related to increased platelet reactivity and activation. Objectives: To compare the effect of oral clopidogrel and aspirin (ASA) on equine platelet function. Animals: Six healthy adult horses. Methods: Horses received clopidogrel (2 mg/kg PO q24h) or ASA (5 mg/kg PO q24h) for 5 days in a prospective randomized cross‐over design. Platelet aggregation responses to adenosine diphosphate (ADP) and collagen via optical aggregometry, and platelet secretion of serotonin (5HT) and production of thromboxane B₂ (TXB₂) by ELISA were evaluated. In horses receiving clopidogrel, high‐performance liquid chromatography analysis for clopidogrel and its carboxylic‐acid metabolite SR 26334 was performed. Results: SR 26334 was identified in all clopidogrel‐treated horses, although the parent compound was not detected. Clopidogrel resulted in decreases in ADP‐induced platelet aggregation persisting for 120 hours after the final dose. ADP‐induced platelet aggregation decreased from a baseline of 70.2 ± 14.7% to a minimum of 15.9 ± 7.7% 24 hours after the final dose (P < .001). Collagen‐induced aggregation decreased from a baseline of 93 ± 9.5% to a minimum of 70.8 ± 16.9% 48 hours after the final dose (P < .001). ASA did not decrease platelet aggregation with either agonist. ASA decreased serum TXB₂ from a baseline value of 1310 ± 1045 to 128 ± 64 pg/mL within 24 hours (P < .01). Conclusions and Clinical Importance: Clopidogrel effectively decreases ADP‐induced platelet aggregation in horses, and could have therapeutic applications for equine diseases associated with platelet activation.     

Effects of two field continuous incremental tests on cardiorespiratory responses in Standardbred trotters

In humans, cardiorespiratory responses are widely evaluated from field incremental exercise tests. On the contrary, equine exercise physiology faces a huge lack of oxygen consumption measurements (VO₂) in field conditions due to technical concerns. The aim of this study was to test the effects of two incremental continuous field tests on cardiorespiratory responses in Standardbred trotters. The two protocols were realized at trot and ended when horses galloped. The tests started at 4.2 m/s (T1) and 6.4 m/s (T2), with speed increments of 1.4 m/s every 3 min for T1 and 0.8 m/s every 2 min for T2. Velocity (v), heart rate (HR) and gas exchanges were recorded continuously, and blood lactate concentration [La^?] was measured before and after tests. Values recorded at the end of the tests were considered as peak values. The v_peak values were 10.6 ± 0.3 and 10.7 ± 0.7 m/s for T1 and T2 respectively. Horses reached higher VO_2peak (T1: 116.6 ± 11.5 ml/min/kg; T2: 88.9 ± 10.2 ml/min/kg; p < 0.05) and HR_peak (T1: 217 ± 5 bpm; T2: 209 ± 3 bpm; p < 0.05) during T1 compared with T2. T1 was significantly longer than T2 (17.5 ± 1.9 vs. 12.9 ± 1.6 min respectively, p < 0.01), and the number of steps entirely ran tended to be different (T1: 5.6 ± 0.6; T2: 6.2 ± 0.8, p = 0.07). Compared to T2, the design of T1 appeared easier to implement and allowed higher cardiorespiratory responses. The relationship between HR‐VO₂ obtained through T1 gave a better correlation between the two variables than T2. These findings suggest that T1 might be better than T2 for evaluating cardiorespiratory adaptations to exercise and for estimating aerobic energy expenditure in exercising trotters.     

Electrophysiological characterization of electrolyte and nutrient transport across the small intestine in horses

The aim of this study was to characterize the transport mechanisms of electrolytes and nutrients across the jejunum of nine healthy horses electrophysiologically. The stripped mucosa was mounted in Ussing chambers and tissue conductances (G_t) and short circuit currents (I_sc) were continuously monitored. After blocking the sodium and potassium channels with amiloride, tetraethylammonium chloride (TEA) and barium, chloride secretion was stimulated by carbachol and forskolin. Subsequently, chloride channels were inhibited by 4,4′‐diisothiocyanato‐stilbene‐2,2′‐disulfonic acid, 5‐nitro‐2‐(3‐phenylpropylamino)benzoic acid, CFTR_inh‐172, N‐(2‐naphtalenyl)‐(3.5‐dibromo‐2.4‐dihydroxyphenyl)methylene glycine hydrazide (GlyH‐101) and glibenclamide and their dose–response effect was investigated. The response to glucose, l ‐alanine and glycyl‐l ‐glutamine was determined at two different mucosal pH values (pH 7.4 and 5.4 respectively). Mean basal I_sc was ?0.47 ± 0.31 μEq/cm²h and mean G_t was 22.17 ± 1.78 mS/cm². Amiloride and TEA did not alter the baseline I_sc. Barium, carbachol and forskolin significantly increased I_sc. Irrespective of the dose, none of the chloride inhibitors changed I_sc. All nutrients induced a significant increase in I_sc with the increase being significantly higher at pH 7.4 than at pH 5.4. In conclusion, there is evidence that chloride secretion in horses may be different from respective transport mechanisms in other species. The glucose absorption is suggestive of a sodium‐dependent glucose cotransporter 1. However, a decrease in luminal pH did not stimulate current response to peptides as shown for other mammals.     

Serum Lipid Modification Related to Exercise and Polyunsaturated Fatty Acid Supplementation in Jumpers and Thoroughbred Horses

The importance of polyunsaturated fatty acids (PUFAs) within the different biological functions of animals has been widely recognized. In this study, exercise and PUFAs supplementation effects on serum triglycerides, total cholesterol, and nonesterified fatty acids (NEFAs) concentration were evaluated in athletic horses. Two sport horse types (10 Italian saddle jumpers and 10 Thoroughbreds) were equally divided into two groups. Jumpers and Thoroughbred experimental groups (A_J and A_T) received 4-week PUFAs supplementation and control groups (B_J and B_T) received no dietary supplement. Before starting the PUFAs supplementation (T0) and at the end of the experimental period (T4), horses were subjected to simulated events. From each subject, blood samples were collected every 7 days at rest, before and after the first test (T0_R and T0_PE), and before and after the second test (T4_R and T4_PE). Higher triglycerides and NEFA concentrations at T0_PE and T4_PE than T0_R and T4_R in both groups were found as a result of exercise (P < .005), but lower triglycerides and NEFA concentrations at T4_PE in group A_J than group B_J (P < .05) and in group A_T (P < .005) than group B_T were found as a result of PUFAs supplementation. Effects of PUFAs supplementation was highlighted by the statistically significant lower triglycerides and NEFA concentrations found at T4_PE than T0_PE in groups A_J (P < .05) and A_T (triglycerides: P < .05; NEFAs: P < .0001).     

The Anti‐microbial Activity of Electrolysed Oxidizing Water against Microorganisms relevant in Veterinary Medicine

Standards of the German Association of Veterinary Medicine (DVG) for the evaluation of chemical disinfectants were used to assess the anti‐microbial efficacy of electrolysed oxidizing water (EOW). Enterococcus faecium, Mycobacterium avium subspecies avium, Proteus mirabilis, Pseudomonas aeruginosa, Staphylococcus aureus and Candida albicans were exposed to anode EOW (pH, 3.0 ± 0.1; oxidation‐reduction potential (ORP), +1100 ± 50 mV; free chlorine, 400 ± 20 mg/l Cl₂) and combined EOW (7 : 3 anode : cathode, v/v; pH, 8.3 ± 0.1; ORP, 930–950 mV; free chlorine, 271 ± 20 mg/l Cl₂). In water of standardized hardness (WSH), all bacterial strains were completely inactivated by a 30 min exposure to maximum 10.0% anode EOW (～40.0 mg/l Cl₂) or 50.0% combined EOW (～135.5 mg/l Cl₂). The sensitivity ranking order for anode EOW to the bacterial test strains was P. mirabilis > S. aureus > M. avium ssp. avium > E. faecium > P. aeruginosa. P. mirabilis and S. aureus decreased to undetectable levels after 5 min of exposure to 7.5% anode EOW (～30.0 mg/l Cl₂). Candida albicans was completely inactivated by a 5‐min exposure to 5.0% anode EOW. Both, anode and combined EOW exhibited no anti‐microbial activities in standardized nutrient broth or after addition of 20.0% bovine serum to the WSH. Further research is necessary to evaluate the efficacy of EOW as a disinfectant under operating conditions in animal production facilities.     

Effect of body weight on the pharmacokinetics of flunixin meglumine in miniature horses and quarter horses

In most species, large variations in body size necessitate dose adjustments based on an allometric function of body weight. Despite the substantial disparity in body size between miniature horses and light‐breed horses, there are no studies investigating appropriate dosing of any veterinary drug in miniature horses. The purpose of this study was to determine whether miniature horses should receive a different dosage of flunixin meglumine than that used typically in light‐breed horses. A standard dose of flunixin meglumine was administered intravenously to eight horses of each breed, and three‐compartmental analysis was used to compare pharmacokinetic parameters between breed groups. The total body clearance of flunixin was 0.97 ± 0.30 mL/min/kg in miniature horses and 1.04 ± 0.27 mL/min/kg in quarter horses. There were no significant differences between miniature horses and quarter horses in total body clearance, the terminal elimination rate, area under the plasma concentration versus time curve, apparent volume of distribution at steady‐state or the volume of the central compartment for flunixin (P > 0.05). Therefore, flunixin meglumine may be administered to miniature horses at the same dosage as is used in light‐breed horses.     

Oxygenation and plasma endothelin‐1 concentrations in healthy horses recovering from isoflurane anaesthesia administered with or without pulse‐delivered inhaled nitric oxide

ObjectiveTo assess oxygenation, ventilation‐perfusion (V/Q) matching and plasma endothelin (ET‐1) concentrations in healthy horses recovering from isoflurane anaesthesia administered with or without pulse‐delivered inhaled nitric oxide (iNO).Study DesignProspective experimental trial.AnimalsHealthy adult Standardbred horses.MethodsHorses were anaesthetized with isoflurane in oxygen and placed in lateral recumbency. Six control (C group) horses were anaesthetized without iNO delivery and six horses received pulse‐delivered iNO (NO group). After 2.5 hours of anaesthesia isoflurane and iNO were abruptly discontinued, inhaled oxygen was reduced from 100% to approximately 30%, and the horses were moved to the recovery stall. At intervals during a 30‐minute period following the discontinuation of anaesthesia, arterial and mixed venous blood gas values, shunt fraction (Qs/Qt), plasma ET‐1 concentration, pulse rate and respiratory rate were measured or calculated. Repeated measures anova and a Bonferroni post hoc test was used to analyze data with significance set at p <0.05.ResultsAt all time points in the recovery period, NO horses maintained better arterial oxygenation (oxygen partial pressure: NO 13.2 ± 2.7–11.1 ± 2.7 versus C 6.7 ± 1.1–7.1 ± 1.1 kPa) and better V/Q matching (Qs/Qt NO 0.23 ± 0.05–0.14 ± 0.06 versus C 0.48 ± 0.03–0.32 ± 0.08%) than C horses. Mixed venous oxygenation was higher in NO for 25 minutes following the discontinuation of anaesthesia (NO 6.3 ± 0.2–4.5 ± 0.07 versus C 4.7 ± 0.6–3.7 ± 0.3 kPa). In both groups of horses arterial oxygenation remained fairly stable; venous oxygenation declined over this time period in the NO group but still remained higher than venous oxygen in the C group. ET‐1 concentrations were higher at most time points in C than NO. Changes in other parameters were either minor or absent.Conclusions and Clinical RelevanceDelivery of iNO to healthy horses during anaesthesia results in better arterial and venous oxygenation and V/Q matching (as determined by lower Qs/Qt) and lower ET‐1 concentrations throughout a 30‐minute anaesthetic recovery period.     

Blood Lymphocyte Subpopulations, Neutrophil Phagocytosis and Proteinogram During Late Pregnancy and Postpartum in Mares

The aim of this study was to evaluate peripheral blood lymphocyte subpopulations, neutrophil phagocytic capacity and proteinogram characteristics in mares, during the last trimester of pregnancy and in postpartum. Measurement of phagocytosis and quantification of T‐lymphocyte subsets were done by flow cytometry. Quantification of T‐lymphocyte subsets was performed with monoclonal antibodies specific for CD2, CD3, CD4 and CD8 cell markers. Natural killer and B‐cell counts were estimated mathematically. Serum proteinogram was obtained by electrophoresis. No significant differences were observed between gestation and postpartum on CD4⁺, CD8⁺ and NK⁺ lymphocyte subsets, CD4 : CD8 ratio and phagocytosis. The percentage of cells expressing CD3 (64.2 ± 1.8) and CD2 (68.4 ± 1.7) (Mean ± SEM) was reduced during gestation vs postpartum (69.7 ± 1.5 and 73.8 ± 1.4 respectively) (p < 0.05). During pregnancy, CD19⁺ (31.6 ± 1.7) was higher than in postpartum (26.2 ± 1.4) (p < 0.05). Total T cells (2911 ± 227 cells/μl), T helper cells (2144 ± 169 cells/μl) and T‐cytotoxic cells (767 ± 68 cells/μl) were depressed in pregnancy, when compared with postpartum (4093 ± 337 cells/μl; 3004 ± 276 cells/μl; 1089 ± 94 cells/μl respectively) (p < 0.01). Total white blood cell count was reduced during pregnancy (8815 ± 427 cells/μl) with respect to postpartum (10742 ± 446 cells/μl) (p < 0.01), while neutrophil count did not change. Total proteins, albumin, α₁,α₂,β₁, β₂, γ globulins and albumin : globulin did not differ. Our results suggest that the physiological immune depression occurring in mares, during gestation might be due to T‐helper and T‐cytotoxic lymphocytes reduction.     

The pharmacokinetics and in vitro cyclooxygenase selectivity of deracoxib in horses

Davis, J. L., Marshall, J. F., Papich, M. G., Blikslager, A. T., Campbell, N. B. The pharmacokinetics and in vitro cyclooxygenase selectivity of deracoxib in horses. J. vet. Pharmacol. Therap. 34 , 12–16. The purpose of this study was to determine the pharmacokinetics of deracoxib following oral administration to horses. In addition, in vitro equine whole blood cyclooxygenase (COX) selectivity assays were performed. Six healthy adult horses were administered deracoxib (2 mg/kg) orally. Plasma samples were collected prior to drug administration (time 0), and 10, 20, 40 min and 1, 1.5, 2, 4, 6, 8, 12, 24, and 48 h after administration for analysis with high pressure liquid chromatography using ultraviolet detection. Following PO administration, deracoxib had a long elimination half‐life (t_1/2k₁₀) of 12.49 ± 1.84 h. The average maximum plasma concentration (C_max) was 0.54 μg/mL, and was reached at 6.33 ± 3.44 h. Bioavailability was not determined because of the lack of an IV formulation. Results of in vitro COX selectivity assays showed that deracoxib was selective for COX‐2 with a COX‐1/COX‐2 ratio of 25.67 and 22.06 for the IC₅₀ and IC₈₀, respectively. Dosing simulations showed that concentrations above the IC₈₀ for COX‐2 would be maintained following 2 mg/kg PO q12h, and above the IC₅₀ following 2 mg/kg PO q24h. This study showed that deracoxib is absorbed in the horse after oral administration, and may offer a useful alternative for anti‐inflammatory treatment of various conditions in the horse.     

Pharmacokinetics of gallium nitrate after oral administration in adult horses--pilot study

Pollina, G. F., Zagotto, G., Maritan, P., Iacopetti, I., Busetto, R Pharmacokinetics of gallium nitrate after oral administration in adult horses – pilot study. J. vet. Pharmacol. Therap.  35 , 489–494. Gallium (Ga), a metal in group IIIA of the periodic table, has shown a remarkable activity against bone resorption and could therefore possibly prove useful in the treatment of certain diseases in sport horses, for example navicular disease. The aim of this study was to gain more information concerning the kinetics of Ga after oral administration of gallium nitrate (GaN) in adult horses. Six horses received a single dose of 10 mg/kg of GaN mixed with the food ration. Absorption was slow (T_max = 10 ± 3 h, T_½abs = 2 ± 0.8 h), and a C_max of 26 ± 11 μg/L was achieved. Excretion followed a one‐phase elimination model, with a long half‐life (T_½el = 52 ± 14 h). By means of a mathematical model, we estimated that the plasmatic levels should reach 93 μg/L (1.33 μm ) at steady state, following the repeated daily administration of 10 mg/kg of GaN. A three times lower concentration has been demonstrated as effective in inhibiting the osteolytic activity of osteoclasts in vitro. The results of this study suggest that the administration of oral GaN at a rate of 10 mg/kg per day may be considered for future clinical studies.     

The bispectral index during recovery from halothane and sevoflurane anaesthesia in horses

ObjectiveTo record the bispectral index (BIS) when horses moved during either halothane or sevoflurane anaesthesia and when they made volitional movements during recovery from these anaesthetics.Study designRandomized prospective clinical study.AnimalsTwenty-five client-owned horses undergoing surgery aged 8.8 (± 5.3; 1–19) years (mean ± SD; range).MethodsBaseline BIS values were recorded before pre-anaesthetic medication (BIS_B) and during anaesthesia (BIS_A) maintained with halothane (group H; n = 12) or sevoflurane (group S; n =13) at approximately 0.8–0.9 × minimum alveolar concentrations (MAC). Bispectral indices were recorded during the surgery when unexpected movement occurred (BIS_MA), during recovery when the first movement convincingly associated with consciousness was observed (BIS_M1) and once sternal recumbency was achieved (BIS_ST).ResultsNo significant difference in BIS_M1 was found between halothane- (85 ± 7; 75–93) and sevoflurane- (87 ± 10; 70–98) anaesthetized horses although BIS_A was significantly (p = 0.0002) lower in group S (62 ± 7; 53–72) than group H (74 ± 7; 60–84). Differences between BIS_M1 and BIS_A were significant in sevoflurane (p = 0.00001) and halothane recipients (p = 0.002) but were greater in group S (25 ± 9; 4–38) compared with group H (12 ± 10; ?9–25). In six of eight horses, BIS_MA values ranged between those recorded during anaesthesia and at first movement.Conclusions and clinical relevanceBispectral indices appear to approximate levels of unconsciousness, suggesting that monitoring the BIS may assist equine anaesthesia. However, it does not predict intra-operative movement.     

Behavioral responses following eight anesthetic induction protocols in horses

Objective To compare behavioral characteristics of induction and recovery in horses anesthetized with eight anesthetic drug protocols. Study design Randomized prospective experimental study. Animals Eight horses, 5.5 ± 2.4 years (mean ± SD) of age, and weighing 505 ± 31 kg. Methods After xylazine pre‐medication, each of eight horses was anesthetized on four occasions using one of eight different anesthetic induction protocols which incorporated various combinations of ketamine (KET), propofol (PRO), and thiopental (THIO): THIO 8 mg kg^?1; THIO 6 mg kg^?1 + PRO 0.5 mg kg^?1; THIO 4 mg kg^?1 + PRO 1 mg kg^?1; THIO 2 mg kg^?1 + PRO 1.5 mg kg^?1; KET 2 mg kg^?1; KET 1.5 mg kg^?1 + PRO 0.5 mg kg^?1; KET 1 mg kg^?1 + PRO 1 mg kg^?1; KET 0.5 mg kg^?1 + PRO 1.5 mg kg^?1. Quality of induction and recovery were scored from 1 (poor) to 5 (excellent), and time taken to achieve lateral recumbency, first movement, sternal recumbency, and standing were evaluated. Results Time taken to achieve lateral recumbency after drug administration differed significantly (p < 0.0001) among the various combinations, being shortest in horses receiving THIO‐8 (mean ± SD, 0.5 ± 0.3 minutes) and longest in horses receiving KET‐2 (1.4 ± 0.2 minutes). The best scores for induction quality were associated with KET‐1.5 + PRO‐0.5, and the worst scores for induction quality were associated with KET‐2, although the difference was not significant. Time to first movement varied significantly among drug protocols (p = 0.0133), being shortest in horses receiving KET‐2 (12.7 ± 3.6 minutes) and longest in horses receiving THIO‐8 (29.9 ± 1.5 minutes). Horses receiving THIO‐8 made the greatest number of attempts to attain sternal posture (6.5 ± 4.7) and to stand (1.6 ± 0.8). Horses in the THIO‐8 treatment also received the poorest recovery scores (3.3 ± 1.0 and 3.0 ± 0.7 for sternal and standing postures, respectively). The best recovery scores were associated with combinations comprised mainly of propofol. Conclusions Combining propofol with either ketamine or thiopental modifies behaviors associated with use of the individual drugs. Clinical relevance Quality of early anesthesia recovery in horses may be improved by some combinations of propofol with either thiopental or ketamine.     

Comparative efficacy of inhaled albuterol between two hand-held delivery devices in horses with recurrent airway obstruction

Reasons for performing study: Studies investigating the clinical efficacy of albuterol administered with the same propellant and commercially available delivery devices in horses with recurrent airway obstruction (RAO) are not currently available. Objectives: To determine the efficacy of aerosolised albuterol administered to horses with RAO by means of 2 commercially available, hand‐held delivery devices. Methods: Ten horses with RAO were kept in a dusty environment and fed mouldy hay to induce airway obstruction. Lung mechanics were measured before and after the procedure. ΔP_max was measured 5 min after administration of 180 µg of albuterol from a pressurised metered dose inhaler, using an aerosol delivery device chosen randomly. This process was repeated every 5 min until maximal bronchodilation was achieved. After a 24 h washout period, lung mechanics data were again collected using the other aerosol delivery device. Results: Aerosolised albuterol induced a significant and rapid bronchodilation in the horses using both aerosol delivery devices. No statistically significant difference in pulmonary function was observed in response to albuterol therapy between the 2 devices. The dose required to achieve 50% of maximal bronchodilation was not statistically different between the 2 devices (173.35 ± 78.35 µg with Device 1 and 228.49 ± 144.99 µg with Device 2, P = 0.26). The decrease in lung resistance tended to be more pronounced after albuterol administration with Device 1 (P = 0.066). Conclusions: Aerosolised albuterol is an effective bronchodilator in horses with recurrent airway obstruction. There is no statistically significant difference between the 2 commercially available aerosol delivery devices in terms of efficacy. Potential relevance: Aerosolised albuterol is effectively delivered using currently available devices leading to maximal bronchodilation in horses with RAO at an average dose of 540 µg.     

Noradrenergic Control of Arginine Vasopressin Release from the Ewe Hypothalamus In Vitro: Sensitivity to Oestradiol

The present study aims at ascertaining the influence of α₁‐adrenoreceptors on arginine vasopressin (AVP) release in vitro and determine whether E₂ modulates the α₁‐adrenoreceptor and AVP interaction. Ten minutes after ewe killing, sagittal midline hypothalamic slices (from the anterior preoptic area to the mediobasal hypothalamus with the median eminence, 2 mm thick, 2 per sheep) were dissected, placed in oxygenated minimum essential media‐α (MEM‐α) at 4°C and within 2 h were singly perifused at 37°C with oxygenated MEM‐α (pH 7.4; flow rate 0.15 ml/min), either with or without E₂ (24 pg/ml). After 4 h equilibration, 10 min fractions were collected for 4 h interposed with 10 min exposure at 60 min to a specific α₁‐adrenoreceptor agonist or antagonist at various doses (0.1–10 mm ). At the end of all perifusions, slices responded to KCl (100 mm ) with AVP efflux (p < 0.05). Release of AVP was enhanced (p < 0.05) by the α₁‐adrenoreceptor agonist (methoxamine 10 mm ; no E₂, n = 7 perifusion chambers: from 14.3 ± 2.7 to 20.9 ± 3.9, with E₂, n = 10: from 10.7 ± 1.2 to 18.4 ± 3.4 pg/ml) or the antagonist (thymoxamine 10 mm ; no E₂, n = 5: from 9.5 ± 3.1 to 30.4 ± 6.0, with E₂, n = 10: from 10.8 ± 0.9 to 39.1 ± 6.3 pg/ml). With the agonist, the response occurred only at 80 min (p < 0.05) both in the presence and absence of E₂. Whereas, after the antagonist, values were higher (p < 0.05) throughout the post‐treatment period (80–170 min) without E₂, but declined by 150 min in the presence of E₂. Furthermore, the response to the α₁‐adrenoreceptor antagonist was greater (p < 0.05; 90–140 min) than the agonist only in the presence of E₂. In conclusion, these results reveal direct α₁‐adrenoreceptor‐mediated control of the hypothalamic AVP neuronal system which is modulated by E₂.     

The effects of ketamine‐midazolam anesthesia on intraocular pressure in clinically normal dogs

Objective To determine the effects of intravenous ketamine‐midazolam anesthesia on intraocular pressure (IOP) in ocular normotensive dogs. Animals Thirteen adult mixed‐breed dogs. Procedures Dogs were randomly assigned to treatment (n = 7) and control (n = 6) groups. Dogs in the treatment group received intravenous ketamine 15 mg/kg and midazolam 0.2 mg/kg and dogs in the control group received intravenous saline. The time of intravenous drug injection was recorded (T₀). Measurements of IOP were then repeated 5 min (T₅) and 20 min (T₂₀) following the intravenous administration of ketamine‐midazolam combination and saline in both groups. Results Measurements showed normal IOP values in both groups. The mean ± SD baseline IOP values for treatment and control groups were 13.00 ± 1.47 and 10.33 ± 2.20, respectively. For baseline IOP values, there was no significant difference between treatment and control groups (P = 0.162). In the treatment group, the subsequent post‐treatment mean ± SD values were 15.64 ± 2.17 (5 min), and 14.92 ± 1.98 (20 min). There was no evidence of statistical difference between baseline values and post‐treatment values after treatment with ketamine‐midazolam (P₅ = 0.139; P₂₀ = 0.442). In control eyes, the mean ± SD values at 5 and 20 min were 10.41 ± 2.01 and 10.16 ± 1.69, respectively. There was no significant difference between baseline values and post‐treatment values in control group (P₅ = 1.000; P₂₀ = 1.000). Conclusion Ketamine‐midazolam combination has no clinically significant effect on IOP in the dog.