A review of clinical approaches to antagonism of alpha2‐adrenoreceptor agonists in the horse

Alpha₂‐adrenoceptor agonists xylazine, romifidine, detomidine and, in some cases, medetomidine and dexmedetomidine, are fundamental drugs used in equine practice. There are situations where the undesirable pharmacodynamic effects (ataxia, prolonged sedation, bradycardia and ileus) or accidental overdose of these drugs may need to be antagonised. The α₂‐adrenoceptor antagonists tolazoline, yohimbine and atipamezole can be used to antagonise undesirable effects. However, despite being effective, α₂‐adrenoceptor antagonists are also not without undesirable pharmacodynamic effects. Excitement, muscle trembling and triggered inappropriate stress responses are a few of the more serious undesirable effects. Horses demonstrate a variable response to the antagonists thus recommending dose rates become fraught with difficulty. It is therefore recommended that the α₂‐adrenoceptor antagonist should be titrated to the desired clinical effect. Consequently, other reversal agents, such as anticholinergics (atropine, glycopyrrolate and hyoscine), have been administered for the treatment of α₂‐adrenoceptor agonist‐induced bradycardia. Anticholinergics cannot be recommended for routine use in horses due to the undesirable cardiovascular effects and potentiation of α₂‐adrenoceptor agonist‐induced gastrointestinal hypomotility. Novel peripheral acting α₂‐adrenoceptor antagonists, such as MK‐467, are currently under scrutiny in veterinary anaesthesia in an effort to antagonise the undesirable effects of α₂‐adrenoceptor agonists without compromising on the level of sedation. This review examines the current literature on the α₂‐adrenoceptor antagonists used in horses and makes recommendations on how to use these drugs safely in an attempt to prevent undesirable pharmacodynamic effects.     

Selectivity of atipamezole, yohimbine and tolazoline for alpha-2 adrenergic receptor subtypes: Implications for clinical reversal of alpha-2 adrenergic receptor mediated sedation in sheep

The α₂-adrenergic receptor antagonists, yohimbine, atipamezole and tolazoline, are used in veterinary medicine as reversal agents for the sedative/hypnotic effects of α₂-agonists. Ruminants have increased sensitivity to the sedative/hypnotic effects of α₂-agonists compared to other species. The receptors mediating the sedative effects of α₂-agonsts are located primarily on locus coeruleus neurons in the pons of the lower brainstem. Four pharmacological subtypes of the α₂-adrenergic receptor (A,B, C and D) have been identified based on differences in ligand affinity. The aim of this study was to: 1) determine the pharmacological profile of atipamezole, yohimbine and tolazoline at the four α₂-adrenergic receptor subtypes and; 2) determine whether these agents differ in their affinities at the α₂-adrenergic receptor present in the sheep brainstem. In inhibition binding studies against the selective α₂-adrenergic receptor ligand [³H]-MK-912, tolazoline showed the lowest affinity for all four α₂-adrenergic receptor subtypes compared to yohimbine and atipamezole. The affinities of yohimbine and atipamezole were similar at the α_2A-, α_2B- and α_2C-adrenergic receptors but differed by approximately 100 fold at the α_2D-adrenergic receptor. Atipamezole had a 100 fold higher affinity at the α_2D-adrenergic receptor when compared to yohimbine. To determine the ligand binding characteristics of these agents at the α₂-adrenergic receptor in sheep brainstem, membranes were labelled with [³H]-MK-912 and inhibition competition curves were performed. Atipamezole showed approximately a 100 fold higher affinity for the sheep brainstem α₂-adrenergic receptor compared to yohimbine which was similar to what was observed for the α_2D-adrenergic receptor in PC12 cells transfected with RG-20. The results from these studies suggest that atipamezole has a high affinity for the α_2D-adrenergic receptor that appears to be the receptor subtype in sheep brainstem.     

Effects of three antagonists on selected pharmacodynamic effects of sublingually administered detomidine in the horse

ObjectiveTo describe the effects of alpha₂-adrenergic receptor antagonists on the pharmacodynamics of sublingual (SL) detomidine in the horse.Study designRandomized crossover design.AnimalsNine healthy adult horses with an average age of 7.6 ± 6.5 years.MethodsFour treatment groups were studied: 1) 0.04 mg kg^?1 detomidine SL; 2) 0.04 mg kg^?1 detomidine SL followed 1 hour later by 0.075 mg kg^?1 yohimbine intravenously (IV); 3) 0.04 mg kg^?1 detomidine SL followed 1 hour later by 4 mg kg^?1 tolazoline IV; and 4) 0.04 mg kg^?1 detomidine SL followed 1 hour later by 0.12 mg kg^?1 atipamezole IV. Each horse received all treatments with a minimum of 1 week between treatments. Blood samples were obtained and plasma analyzed for yohimbine, atipamezole and tolazoline concentrations by liquid chromatography-mass spectrometry. Behavioral effects, heart rate and rhythm, glucose, packed cell volume (PCV) and plasma proteins were monitored.ResultsChin-to-ground distance increased following administration of the antagonists, however, this effect was transient, with a return to pre-reversal values as early as 1 hour. Detomidine induced bradycardia and increased incidence of atrioventricular blocks were either transiently or incompletely antagonized by all antagonists. PCV and glucose concentrations increased with tolazoline administration, and atipamezole subjectively increased urination frequency but not volume.Conclusions and clinical relevanceAt the doses administered in this study, the alpha₂-adrenergic antagonistic effects of tolazoline, yohimbine and atipamezole on cardiac and behavioral effects elicited by SL administration of detomidine are transient and incomplete.     

Antagonistic effects of atipamezole,yohimbine, and prazosin on xylazine-induced diuresis in clinically normal cats

This study aimed to investigate and compare the antagonistic effects of atipamezole, yohimbine, and prazosin on xylazine-induced diuresis in clinically normal cats. Five cats were repeatedly used in each of the 9 groups. One group was not medicated. Cats in the other groups received 2 mg/kg BW xylazine intramuscularly, and saline (as the control); 160 μg/kg BW prazosin; or 40, 160, or 480 μg/kg BW atipamezole or yohimbine intravenously 0.5 h later. Urine and blood samples were collected 10 times over 8 h. Urine volume, pH, and specific gravity; plasma arginine vasopressin (AVP) concentration; and creatinine, osmolality, and electrolyte values in both urine and plasma were measured. Both atipamezole and yohimbine antagonized xylazine-induced diuresis, but prazosin did not. The antidiuretic effect of atipamezole was more potent than that of yohimbine but not dose-dependent, in contrast to the effect of yohimbine at the tested doses. Both atipamezole and yohimbine reversed xylazine-induced decreases in both urine specific gravity and osmolality, and the increase in free water clearance. Glomerular filtration rate, osmolar clearance, and plasma electrolyte concentrations were not significantly altered. Antidiuresis of either atipamezole or yohimbine was not related to the area under the curve for AVP concentration, although the highest dose of both atipamezole and yohimbine increased plasma AVP concentration initially and temporarily, suggesting that this may in part influence antidiuretic effects of both agents. The diuretic effect of xylazine in cats may be mediated by α₂-adrenoceptors but not α₁-adrenoceptors. Atipamezole and yohimbine can be used as antagonistic agents against xylazine-induced diuresis in clinically normal cats.     

Endocrine Changes after Mating in Pregnant and Non-Pregnant Llamas and Alpacas

Plasma concentrations of oestradiol-17ß, progesterone, 15-keto–dihydro–PGF_2α and luteinizing hormone (LH) were monitored in llamas and alpacas after mating with an intact male. Concentrations of LH and PGF_2α metabolite were high immediately after copulation. Ovulation occurred in 92% of the animals. The first significant increases in progesterone were recorded on day 4 after mating. In non-pregnant animals the lifespan of the corpus luteum was estimated to be 8–9 days. Luteolysis occurred in association with the release of PGF_2α. In pregnant animals, a transient decrease in progesterone concentrations was observed between days 8 and 18 in both species. No significant changes in PGF_2α secretion were registered during this period. Oes– tradiol–17ß concentrations were high on the day of mating, declined to low values on day 4, and started to increase again on day 8. Peak values after luteolysis in non-pregnant animals were significantly higher than those registered in pregnant ones. Furthermore, concentrations of oestradiol-17ß were elevated for a longer period in non–pregnant than in pregnant animals. The results suggest that progesterone from the corpus luteum exerts a negative influence on follicular activity in pregnant animals by reducing oes– tradiol-17ß secretion.     

The α2A‐adrenoceptor subtype plays a key role in the analgesic and sedative effects of xylazine

Xylazine, the classical α₂‐adrenoceptor (α₂‐AR) agonist, is still used as an analgesic and sedative in veterinary medicine, despite its low potency and affinity for α₂‐ARs. Previous pharmacological studies suggested that the α_2A‐AR subtype plays a role in mediating the clinical effects of xylazine; however, these studies were hampered by the poor subtype‐selectivity of the antagonists used and a lack of knowledge of their bioavailability in vivo. Here, we attempted to elucidate the role of the α_2A‐AR subtype in mediating the clinical effects of xylazine by comparing the analgesic and sedative effects of this drug in wild‐type mice with those in α_2A‐AR functional knockout mice using the hot‐plate and open field tests, respectively. Hippocampal noradrenaline turnover in both mice was also measured to evaluate the contribution of α_2A‐AR subtype to the inhibitory effect of xylazine on presynaptic noradrenaline release. In wild‐type mice, xylazine (10 or 30 mg/kg) increased the hot‐plate latency. Furthermore, xylazine (3 or 10 mg/kg) inhibited the open field locomotor activity and decreased hippocampal noradrenaline turnover. By contrast, all of these effects were abolished in α_2A‐AR functional knockout mice. These results indicate that the α_2A‐AR subtype is mainly responsible for the clinical effects of xylazine.     

Partial intravenous anaesthesia in the horse: a review of intravenous agents used to supplement equine inhalation anaesthesia. Part 2: opioids and alpha‐2 adrenoceptor agonists

ObjectiveTo review the literature with regard to the use of different intravenous agents as supplements to inhalational anaesthesia in horses. The Part 2 of this review will focus in the use of opioids and a₂-agonists.Databases usedPubmed and Web of Science. Search terms: horse, inhalant anaesthesia, balanced anaesthesia, partial intravenous anaesthesia, opioids, morphine, pethidine, butorphanol, methadone, fentanyl, alfentanil, remifentanil, sufentanil, xylazine, romifidine, detomidine, medetomidine and dexmedetomidine.ConclusionsDifferent drugs and their combinations can be administered systemically in anaesthetized horses aiming to reduce the amount of the volatile agent while improving the recovery qualities and providing a multimodal analgesic approach. However, full studies as to whether these techniques improve cardiopulmonary status are not always available and potential disadvantages should also be considered.     

Integrin heterodimer α9β1 is localized on the surface of porcine spermatogonial stem cells in the undifferentiated state

A previous study found that undifferentiated porcine spermatogonial stem cells (SSCs) did not adhere to tenascin C, indicating that the integrin α₉ and β₁ subunits are inactive on the surface of porcine SSCs. However, that study used recombinant tenascin C without FNIII‐like repeats. Therefore, this study re‐evaluated the existence of integrin α₉β₁ actively functioning on the plasma membrane of porcine SSCs using full‐length native tenascin C with FNIII‐like repeats. The localization and function of the integrin heterodimer were confirmed using immunocytochemistry, attachment and antibody inhibition assays. In undifferentiated porcine SSCs with integrin α₉β₁ on the cell surface, adhesion to native tenascin C was significantly higher compared with cells lacking native tenascin C and functional blocking of integrin α₉β₁ significantly inhibited the attachment to native tenascin C compared with no functional blocking. Accordingly, we confirmed that the integrin α₉ and β₁ subunits function as an active heterodimer on the surface of porcine SSCs in the undifferentiated state.     

Intraluminal Pressure Variations in the Isthmus of the Porcine Oviduct after Intrauterine Insemination with Saline,Oestrogen Solution or Boar Seminal Plasma

The purpose of this study was to investigate if an intrauterine deposition of saline, boar seminal plasma, or an oestrogen solution containing 11.5 µg oestrogens affected the intraluminal pressure in the isthmus of the oviduct in unrestrained gilts. In order to monitor variations in intraluminal pressure, 2 ultra-miniature pressure sensors, located at 2 different points along the same isthmus were used. After an initial recording period, either saline, boar seminal plasma, or the oestrogen solution was deposited directly into the uterus. Intraluminal pressure recordings were conducted up to 6 h after insemination, and blood samples, for monitoring oestradiol-17B and 15-ketodihydroprostaglandin F_2α levels, were collected. None of the inseminates had any consistent effect on the intraluminal pressure in the porcine oviduct. After deposition of the oestrogen solution, increases in the circulating levels of both oestradiol-17B and 15-ketodihydropro- staglandin F_2α were seen.     

Antagonistic effects of atipamezole and yohimbine on medetomidine-induced diuresis in healthy dogs

This study aimed to investigate and compare the antagonistic effects of atipamezole and yohimbine on medetomidine-induced diuresis in healthy dogs. Five dogs were used repeatedly in each of 8 groups. One group was not medicated. Dogs in the other groups received 20 μg/kg of medetomidine intramuscularly and, 0.5 h later, saline (as the control injection), 50, 100, or 300 μg/kg of atipamezole, or 50, 100, or 300 μg/kg of yohimbine intramuscularly. Urine and blood samples were taken 11 times over 24 h for measurement of the following: urine volume, specific gravity, and creatinine concentration; urine and plasma osmolality; urine and plasma concentrations of electrolytes and arginine vasopressin (AVP); and the plasma concentration of atrial natriuretic peptide (ANP). Both atipamezole and yohimbine antagonized the diuretic effect of medetomidine, inhibiting medetomidine-induced decreases in urine specific gravity, osmolality, and concentrations of creatinine, sodium, potassium, chloride, and AVP and reversing both the medetomidine-induced increase in plasma concentrations of sodium, potassium, and chloride and the medetomidine-induced decrease in the plasma AVP concentration. Atipamezole significantly stimulated ANP release. The antidiuretic action of yohimbine was more potent than that of atipamezole but was not dose-dependent, in contrast to the action of atipamezole. The effects of these drugs may not be due only to actions mediated by α₂-adrenoceptors.     

Peritoneal concentrations of transforming growth factor beta in horses with colic

Reasons for performing the study: In man, peritoneal transforming growth factor beta (TGF‐β) is associated with peritoneal diseases and subsequent adhesion formation. No studies on plasma and peritoneal TGF‐β concentrations in horses with colic are available. Objectives: 1) To determine both plasma and peritoneal TGF‐β₁ and TGF‐β₃ concentrations in horses with different types of colic (not previously subjected to abdominal surgery); 2) to compare these concentrations according to the type of peritoneal fluid (transudate, modified transudate and exudate); and 3) to compare and correlate plasma and peritoneal concentrations of TGF‐β₁ and TGF‐β₃ and the types of peritoneal fluid according to the colic group and outcome. Methods: Peritoneal fluid and plasma samples from 78 horses with colic and 8 healthy horses were obtained. Patients were classified according to diagnosis (obstructions, enteritis, ischaemic disorders and peritonitis), peritoneal fluid analysis (transudate, modified transudate and exudate), and outcome (survivors and nonsurvivors). Plasma and peritoneal TGF‐β₁ and TGF‐β₃ concentrations were determined by ELISA. Data were analysed by parametric and nonparametric tests. P≤0.05 was considered as statistically significant. Results: Concentrations of peritoneal fluid TGF‐β₁ were significantly (P = 0.01) higher in horses with peritonitis in comparison with all other colic groups and controls. Horses with ischaemic lesions had significantly (P = 0.01) higher concentrations of peritoneal TGF‐β₁ in comparison with controls and the group of horses with obstructions. Peritoneal TGF‐β₁ concentration also was significantly (P = 0.01) higher in exudates in comparison with transudates. Peritoneal TGF‐β₁ and TGF‐β₃ concentrations and plasma TGF‐β₁ concentration were significantly increased in nonsurvivors compared to survivors (P = 0.001, P = 0.004 and P = 0.05, respectively). Conclusions: Peritoneal TGF‐β₁ concentration was higher in horses with severe gastrointestinal diseases (ischaemic intestinal lesions and peritonitis), in horses with an altered peritoneal fluid (exudate), and in nonsurvivors. Potential relevance: Peritoneal TGF‐β concentration increases in horses with severe gastrointestinal disease as an anti‐inflammatory response.     

The influence of atipamezole on the cardiovascular effects of detomidine in horses

The reversal of the cardiovascular effects of the α₂-adrenoceptor agonist detomidine by the α₂-antagonist atipamezole was studied. Nine horses were given detomidine 20 μg/kg iv. On a separate occasion they were given atipamezole 100 μg/kg iv 15 mins after the detomidine injection. Blood gas tensions were measured and clinical signs of sedation were also observed. Bradycardia and the frequency of heart blocks induced by detomidine were reduced after atipamezole and blood pressure decreased. These reversal effects of atipamezole were of short duration (a few minutes) at the dose level tested. Two of the nine horses exhibited premature depolarisations after administration of detomidine, but not after atipamezole injection. PaO₂ decreased and PaCO₂ increased slightly after detomidine injection, but the arterial pH was within reference values or slightly elevated. Administration of atipamezole did not alter these values. Base excess rose after detomidine, and it decreased more quickly towards the baseline level, when the horses were given detomidine alone. No clinical adverse effects were seen from the administration of atipamezole. Atipamezole may be beneficial, if detomidine-induced bradycardia needs to be reversed in horses.     

Effects of GnRH in combination with PGF2α on the dynamics of follicular and luteal cells in post-pubertal Holstein heifers

Holstein heifers were randomly allotted by weight, age and body condition score to one of three treatments to test the hypothesis that GnRH administration concurrent with PGF_2α injection would advance follicle or corpus luteum (CL) development parallel to an induced luteolysis of the pre-existing CL. Heifers in the control group (n = 14) received two treatments of PGF_2α(25 mg, im) given 10 days apart. Groups 2 (n = 14) and 3 (n = 14) received an additional treatment of GnRH (100 μg, im) after the first and second PGF_2α respectively. Estrus detection began immediately after PGF_2α and continued for 80 h. Blood sampling was initiated 7 days prior to the first PGF_2α (day − 7) and continued on days 0, 7, 10 (prior to the second PGF_2α), 17 and 24. Heifers were artificially inseminated after the second PGF_2α and pregnancy diagnosed at 60 days. There was a trend (P < .10) toward a lower estrus response in group 3 when compared to the other groups. Pregnant heifers in group 2 had lower progesterone (0.44 ± 0.09 vs. 1.72 ± 0.56 ng/ml) a week after the second PGF_2α than the non-pregnant animals in that group (P < .05). Similar results were observed in the control group but only within the responding heifers (0.61 ± 0.08 vs. 0.93 ± 0.03 ng/ml; P < .05). Progesterone in heifers in group 2 remained high on day 0, 7, and 10 (1.48 ± 0.37, 1.23 ± 0.39, 1.96 ± 0.36 ng/ml) in spite of the treatment with PGF_2α. This data suggest that administration of GnRH following PGF_2α alters bovine luteal and/or follicular cell function.     

Improving a Complement-fixation Test for Equine Herpesvirus Type-1 by Pretreating Sera with Potassium Periodate to Reduce Non-specific Hemolysis

Non-specific hemolysis has often been observed during complement-fixation (CF) tests for equine herpesvirus type-1 (EHV-1), even when the sera have virus-specific CF antibodies. This phenomenon has also been reported in CF tests for various infectious diseases of swine. We found that the sera from 22 of 85 field horses (25.9%) showed non-specific hemolysis during conventional CF testing for EHV-1. Because pretreatment of swine sera with potassium periodate (KIO₄) improves the CF test for swine influenza, we applied this method to horse sera. As we expected, horse sera treated with KIO₄ did not show non-specific hemolysis in the EHV-1 CF test, and precise determination of titers was achieved.     

Regulation of matrix metalloproteinase-9 protein expression by 1α,25-(OH)2D3 during osteoclast differentiation

To investigate 1α,25-(OH)₂D₃ regulation of matrix metalloproteinase-9 (MMP-9) protein expression during osteoclast formation and differentiation, receptor activator of nuclear factor κB ligand (RANKL) and macrophage colony-stimulating factor (M-CSF) were administered to induce the differentiation of RAW264.7 cells into osteoclasts. The cells were incubated with different concentrations of 1α,25-(OH)₂D₃ during culturing, and cell proliferation was measured using the methylthiazol tetrazolium method. Osteoclast formation was confirmed using tartrate-resistant acid phosphatase (TRAP) staining and assessing bone lacunar resorption. MMP-9 protein expression levels were measured with Western blotting. We showed that 1α,25-(OH)₂D₃ inhibited RAW264.7 cell proliferation induced by RANKL and M-CSF, increased the numbers of TRAP-positive osteoclasts and their nuclei, enhanced osteoclast bone resorption, and promoted MMP-9 protein expression in a concentration-dependent manner. These findings indicate that 1α,25-(OH)₂D₃ administered at a physiological relevant concentration promoted osteoclast formation and could regulate osteoclast bone metabolism by increasing MMP-9 protein expression during osteoclast differentiation.     

Effects of α2-adrenergic drugs on blood platelets in sheep

Xylazine (0.2 mg/kg, iv) alone or preceded by atipame-zole (0.125 μg/kg, iv) or by aspirin (10 μg/kg, iv) was administered to 18 sheep. Medetomidine (60 μg/kg, iv) was also administered to 12 sheep. Xylazine, but not medetomidine, significantly reduced the number of platelets. Both atipamezole and aspirin prevented this reduction. It was concluded that α₂-agonists would seem to produce platelet aggregation that may contribute to the development of the respiratory changes that follow the administration of α₂-agonists in sheep, but probably not always to a degree that could result in a significant decrease in the number of circulating platelets.     

Intrafollicular Concentrations of Steroid Hormones and PGF2α in Relation to Follicular Development in the Mares during the Breeding Season

The concentrations of androstenedione, estradiol-17β, progesterone and PGF_2α contained in the follicular fluid produced by the follicles in collected ovaries of mares that have had estrous phase during the breeding season were measured and analyzed the relation between the growth stage of follicles and the hormone levels in the follicular fluid. An ultrasonographic diagnostic instrument was used to measure the diameter of the follicles in order to categorize the follicles into three groups the following: 8 small follicles (from 1.0 to less than1.5 cm), 8 medium follicles (from 1.5 to less than 3.0 cm), and 8 large follicles (from 3.0 to 5.0 cm), respectively. The analysis of the follicular fluid in ovaries of estrous mares showed that the concentrations of androstenedione were significantly higher in the medium or large follicles than in the small follicles and the concentrations of estradiol-17β were significantly higher in larger follicles than in the small or medium follicles (P<0.05). The concentrations of progesterone and PGF_2α, on the other hand, did not significantly vary regardless of follicluar size. In the follicles within the mare ovaries that have had estrous stage, the concentrations of the hormones related the ovulation, namely androstenedione and estradiol-17β, were higher with larger follicles.     

Differences in Pulmonary Functional Indices Derived from the Single-Breath Diagram for CO2 (SBD-CO2) in Horses Related to Age,Sex and Usage

Although pulmonary function tests have been used to evaluate horses with clinically normal lungs and those with recurrent airway obstruction (RAO), comprehensive studies of equine respiratory function, considering factors such as sex, age and usage are not available. Studies on the influence of these factors on pulmonary function in healthy horses are required for interpretation of measurements made in those with respiratory disease. The study was performed with 63 warmblood horses and the status of their pulmonary health was evaluated by clinical examination. The functional aspect of pulmonary health was assessed by indices derived from the single-breath diagram for CO₂ (SBD-CO₂). Differences in pulmonary functional indices between the sexes, age groups and usage groups adjusted for pulmonary health were analysed with hierarchical linear models. It was shown that the effects on pulmonary function of age, sex and usage of a horse were significant and have to be considered when establishing the true pulmonary functional status of a horse suffering from RAO. The multivariate statistical model used included the covariates age, sex and sporting discipline of the horses and accounted for the complex, non-linear interactions between the different covariates.     

Presence of a Temperature Gradient Among Genital Tract Portions and the Thermal Changes Within These Portions Over the Estrous Cycle in Beef Cows

The aim of the present study was to describe the temperature of the different portions of the female genital tract and their relation to rectal temperature and to investigate the effect of steroid hormones profiles on these variables over the estrous cycle in cattle. Four nonpregnant Japanese Black cows were investigated daily over two successive estrous cycles using a digital thermometer with a long probe and rounded-end sensor to record the temperature of the rectum (RT), vagina (VT), cervix (CT), uterine body (UBT) and uterine horns (UHT). Blood samples were collected immediately before temperature recording to assay peripheral levels of progesterone (P₄) and estradiol-17β (E₂). Moreover, transrectal ultrasonography was carried out after temperature recording to monitor the ovulatory follicle and track ovulation. During the experiment, the ambient temperature and relative humidity were recorded for further calculation of the temperature humidity index (THI). The temperature within the genital tracts in these cows progressively increased towards the uterine horns from the vagina. The VT, CT, UBT and UHTs were significantly higher in association with peripheral P₄ concentrations greater than 4 ng/ml (mid-luteal phase) when compared with lower peripheral P₄ concentrations. The VT was more significantly (P<0.01) correlated to the CT, UBT and UHTs than RT. In conclusion, a temperature gradient was present among the vagina, cervix and uterus over the estrous cycle, and changes in peripheral P₄ concentrations were associated with the thermal variations within these portions. The VT could be more beneficial than RT in monitoring temperature of deeper portions of the female genital tract in bovine.     

In vitro evaluation of the effect of the opioid antagonist N-methylnaltrexone on motility of the equine jejunum and pelvic flexure

REASONS FOR PERFORMING STUDY: Although potent analgesics, opioids decrease intestinal activity, leading to ileus in many species. N-methylnaltrexone (MNTX), an opioid antagonist which does not cross the blood-brain barrier and antagonises the morphine effect on the intestine, directly stimulates motility and restores function without affecting analgesic properties. While its use has been reported in human subjects, there is no information with regard to its usage in the horse. OBJECTIVES: To determine whether MNTX has an effect on contractile activity of the equine jejunum and pelvic flexure. METHODS: Using circular smooth muscle strips obtained from 8 mature horses, increasing concentrations of MNTX were added to tissue baths in the range of 1 x 10(-9) to 1 x 10(-5) mol/l, and contractile responses were recorded for 3 mins. Data were analysed using a repeated measures ANOVA to determine whether there was a significant drug effect compared to baseline activity. Data were analysed between the jejunum and pelvic flexure using a Mann-Whitney U test. Statistical significance was established as P < 0.05. RESULTS: The administration of MNTX significantly increased the contractile frequency and amplitude at all concentrations relative to baseline (P < 0.0001) for the jejunum. The response was greatest at 1 x 10(-7) mol/l (P = 0.0005), with a mean difference from baseline of 115.12 g/cm2. The highest concentration evaluated (1 x 10(-5) mol/l) had a mean contractile strength of 69.76 g/cm2, which was significantly greater than baseline activity (P = 0.04). A significant increase in contractile activity for the colon was detected at 3 x 10(-7) mol/l and all subsequent concentrations (P < 0.04). Unlike the jejunum, the contractile activity of the pelvic flexure increased progressively with the addition of each subsequent concentration. CONCLUSIONS: N-methylnaltrexone has a direct effect on circular smooth muscle of the equine jejunum and pelvic flexure resulting in an increase in contractile activity. POTENTIAL RELEVANCE: N-methylnaltrexone could potentially be used in conjunction with morphine to provide potent and effective analgesia without compromising intestinal function. Further in vivo investigations are required to determine whether this agent antagonises morphine's effect on motility.