Pharmacokinetics of ceftiofur sodium in equine pregnancy.

Eleven pregnant pony mares (D270-326) were administered ceftiofur sodium intramuscularly at 2.2 mg/kg (n = 6) or 4.4 mg/kg (n = 5), once daily. Plasma was obtained prior to ceftiofur administration and at 0.5, 1, 2, 4, 8, 12, and 24 hr after administration. Eight pony mares were re-enrolled in the study at least 3 days from expected foaling to ensure steady-state concentrations of drug at the time of foaling. Mares were administered ceftiofur sodium (4.4 mg/kg, IM) daily until foaling. Parturition was induced using oxytocin 1 hr after ceftiofur sodium administration. Allantoic and amniotic fluid, plasma, and colostrum samples were collected at time of foaling. Serial foal plasma samples were obtained. Placental tissues were collected. Desfuroylceftiofur acetamide (DCA) concentrations were measured in samples by high-performance liquid chromatography (HPLC). Mean (±SD) peak serum concentrations of DCA were 3.97 ± 0.50 µg/ml (low dose) and 7.45 ± 1.05 µg/ml (high dose). Terminal half-life was significantly (p = .014) shorter after administration of the low dose (2.91 ± 0.59 hr) than after administration of the high dose (4.10 ± 0.72 hr). The mean serum concentration of DCA from mares at time of foaling was 7.96 ± 1.39 µg/ml. The mean DCA concentration in colostrum was 1.39 ± 0.70 µg/ml. DCA concentrations in allantoic fluid, amniotic fluid, placental tissues, and foal plasma were below the limit of quantification (<0.1 µg/ml) and below the minimum inhibitory concentration of ceftiofur against relevant pathogens. These results infer incomplete passage of DCA across fetal membranes after administration of ceftiofur sodium to normal pony mares.

Factors affecting live foal rates of Thoroughbred mares that undergo manual twin elimination.

REASONS FOR PERFORMING STUDY: Mares diagnosed with twin vesicles at 13-17 days after ovulation commonly have one of 2 vesicles manually reduced. It is not known whether vesicle location (adjacent vs. nonadjacent), mare age, mare reproductive status, parity, month of breeding or mare plasma progesterone concentration affects live foal rates. OBJECTIVES: To determine factors associated with a positive outcome (live foal) in mares undergoing manual twin reduction between 13 and 17 days post ovulation when performed by a single operator. STUDY DESIGN: Retrospective case-control study. METHODS: Breeding records and the Jockey Club records of registered Thoroughbreds were used to evaluate factors affecting the outcome of pregnancies in mares undergoing twin elimination and mares with singleton pregnancies. Thoroughbred mares with twin pregnancies (n = 129) were matched by age, parity, farm location and month bred with mares diagnosed with a singleton pregnancy (n = 127). The effects of location of embryonic vesicles, mare age, reproductive status, parity, month of breeding, vesicle size and plasma progesterone concentration at pregnancy diagnosis on live foal rate were examined. RESULTS: Position of embryonic vesicles at time of manual elimination, parity and month bred had no effect on live foal rate. Live foal rates in mares >9 years of age were lower (71.8%) than in all mares ≤9 years (87.1%; P<0.05). Mares >9 years of age that had a twin reduced lost more pregnancies (34.8%) than age-matched control mares (20.0%; P<0.005). Mean plasma progesterone concentration of twin-reduced mares was greater than in control mares when compared on the same day post ovulation. Plasma progesterone concentrations did not differ between mares that lost their pregnancy and those that delivered a live foal. CONCLUSIONS: Mare age of >9 years is associated with decreased pregnancy rate after twin reduction. POTENTIAL RELEVANCE: Furthering the understanding of factors that affect live foal outcome following manual twin elimination in mares.

Relationship between infection, inflammation and premature parturition in mares with experimentally induced placentitis.

REASONS FOR PERFORMING THE STUDY: Ascending placentitis results in premature birth and high foal mortality. By understanding how placentitis induces premature delivery, it may be possible to develop diagnostic markers and to delay premature delivery pharmacologically, thereby decreasing perinatal foal mortality. OBJECTIVE: To identify relationships between bacterial infection, inflammation and premature parturition in mares with experimentally induced placentitis. MATERIALS AND METHODS: Experiment 1: Concentrations of allantoic fluid prostaglandins (PGs) F2alpha and E2 were measured in 8 mares after intracervical inoculation with Streptococcus equi ssp. zooepidemicus (at Days 285-291 of gestation) until parturition and compared with controls (n = 4). Experiment 2: mRNA expression of interleukin (IL)-1beta, IL-6, tumour necrosis factor (TNF)-alpha and IL-8 in the chorioallantois from inoculated mares in Experiment 1 were compared with 7 mares that foaled normally. RESULTS: Bacterial inoculation resulted in 7 aborted fetuses and birth of one premature, viable foal. Infection was associated with inflammation of the chorioallantois in the region of the cervical star, isolation of bacteria and high concentrations of PGE2 and PGF2alpha in allantoic fluid obtained within 48 h of delivery (P = 0.04). Chorioallantois from all mares expressed mRNA for IL-8, TNF-alpha, IL-6 and IL-1beta. Experimentally infected mares expressed more mRNA for IL-6 (P = 0.003) and IL-8 (P = 0.009) in the cervical star region and more mRNA for IL-6 (P = 0.004) in tissues from placental horns than control mares. CONCLUSIONS AND CLINICAL RELEVANCE: Bacterial placentitis may result in liberation of cytokines from the chorioallantois and prostaglandin formation leading to abortion or birth of a precociously mature foal.

Advances in the diagnosis and treatment of chronic infectious and post-mating-induced endometritis in the mare.

CONTENTS: Rapid physical uterine clearance is paramount for fertility. Mares that are unable to clear the by-products of insemination or foaling quickly may develop post-mating-induced or acute endometritis. If endometritis is not promptly resolved, the infection can become chronic. Endometritis can be difficult to identify because clinical signs, ultrasonographic and laboratory findings can vary between uterine pathogens. Some micro-organisms are associated with an influx of neutrophils and fluid into the uterine lumen while others are associated with only heavy debris on cytological specimens. Identifying the inciting cause may require more than swabbing the endometrium. Culturing endometrial biopsy tissue or uterine fluids are more sensitive methods for identifying Escherichia coli than culture swab while endometrial cytology identifies twice as many mares with acute inflammation than uterine culture swab. While post-mating-induced endometritis is classically treated with uterine irrigation and ecbolics and acute endometritis is treated with either systemic or intra-uterine antibiotics, these therapies are not always effective in resolving chronic uterine inflammation or infections. Mucolytics can be used to break up mucus produced by an irritated endometrium, steroids can modulate the inflammatory response associated with insemination and buffered chelating agents can remove biofilm, a protective mechanism used primarily by gram-negative organisms and yeast to evade the host immune response.

Ascending placentitis in the mare: an update.

CONTENTS: Ascending placentitis is a common cause of premature birth, abortion and delivery of compromised, ill foals. Recent experimental models have investigated diagnostic procedures and treatment strategies in an attempt to improve live foal rate. Diagnostics such as transrectal and transabdominal ultrasonography are used to evaluate foetal well-being and placental separation, while measurement of plasma progestins or oestrogen identifies a stressed or hypoxic foetus. Treatment is directed at stopping spread of infection, maintaining uterine quiescence and blocking production of pro-inflammatory cytokines. It must be instituted early if a pregnancy is to be saved. Treatments include antibiotics, tocolytics and immunomodulators. Prompt, aggressive treatment with antibiotics has improved foal viability in experimental models of placentitis.

Treatment efficacy of trimethoprim sulfamethoxazole, pentoxifylline and altrenogest in experimentally induced equine placentitis.

The objective was to determine if long-term treatment with trimethoprim sulfamethoxazole (antimicrobial), pentoxifylline (anti-inflammatory/anti-cytokine) and altrenogest (synthetic progestin), would improve pregnancy outcome in mares with experimentally induced placentitis. Seventeen normal, pregnant pony mares were enrolled in the study at 280-295 d of pregnancy. Placentitis was induced in all mares by intra-cervical inoculation of Streptococcus equi subsp. zooepidemicus (10(7) CFU). Five mares served as infected, untreated control animals (Group UNTREAT). Twelve mares (Group TREAT) were infected and given trimethoprim sulfamethoxazole (30 mg/kg, PO, q 12h), pentoxifylline (8.5 mg/kg, PO, q 12h) and altrenogest (0.088 mg/kg, PO, q 24h) from the onset of clinical signs to delivery of a live foal or abortion. Blood samples were cultured from all foals at delivery and fetal stomach and thoracic contents were obtained for culture from dead fetuses. More mares in Group TREAT delivered viable foals (10/12; 83%; P < 0.05) than mares in Group UNTREAT (0/5; 0%). Ten of 12 foals (83%) in Group TREAT had negative blood cultures at birth. All foals in Group UNTREAT (5/5; 100%) had positive cultures from one or more samples (blood, stomach contents, and thoracic fluid). Bacteria were recovered from uterine culture samples in both groups. Streptococcus equi subsp. zooepidemicus was the predominant organism recovered from fetal/foal or mare culture samples. The authors inferred that administration of trimethoprim sulfamethoxazole, pentoxifylline and altrenogest may improve the viability of foals from mares with experimentally induced placentitis.

The trianvil test apparatus: measurement of shear strength under pressure.

An experimental apparatus has been developed for performing shear tests on specimens held under moderately high hydrostatic pressures (up to the order of 10 GPa). This testing procedure experimentally determines the pressure dependent shear strength of thin foil specimens. This information is necessary for models of materials subjected to extreme pressures and can assist in model validation for models such as discrete dislocation dynamics simulations, among others. This paper reports the development of the experimental procedures and the results of initial experiments on thin foils of polycrystalline Ta performed under hydrostatic pressures ranging from 2 to 4 GPa. Subsequent characterization of the samples held under pressure established that the procedure described herein represents a reliable method to impose nearly uniform hydrostatic pressure on thin foil specimens. Both yielding and hardening behavior of Ta are observed to be sensitive to the imposed pressure.

Clinical and subclinical endometritis in the mare: both threats to fertility.

Endometritis, a major cause of mare infertility arising from failure to remove bacteria, spermatozoa and inflammatory exudate post-breeding, is often undiagnosed. Defects in genital anatomy, myometrial contractions, lymphatic drainage, mucociliary clearance, cervical function, plus vascular degeneration and inflamm-ageing underlie susceptibility to endometritis. Diagnosis is made through detecting uterine fluid, vaginitis, vaginal discharge, short inter-oestrous intervals, inflammatory uterine cytology and positive uterine culture. However, these signs may be absent in subclinical cases. Hypersecretion of an irritating, watery, neutrophilic exudate underlies classic, easy-to-detect streptococcal endometritis. In contrast, biofilm production, tenacious exudate and focal infection may characterize subclinical endometritis, commonly caused by Gram-negative organisms, fungi and staphylococci. Signs of subclinical endometritis include excessive oedema post-mating and a white line between endometrial folds on ultrasound. In addition, cultures of uterine biopsy tissue or of small volume uterine lavage are twice as sensitive as guarded swabs in detecting Gram-negative organisms, while uterine cytology is twice as sensitive as culture in detecting endometritis. Uterine biopsy may detect deep inflammatory and degenerative changes, such as disruption of the elastic fibres of uterine vessels (elastosis), while endoscopy reveals focal lesions invisible on ultrasound. Mares with subclinical endometritis require careful monitoring by ultrasound post-breeding. Treatments that may be added to traditional therapies, such as post-breeding uterine lavage, oxytocin and intrauterine antibiotics, include lavage 1-h before mating, carbetocin, cloprostenol, cervical dilators, systemic antibiotics, intrauterine chelators (EDTA-Tris), mucolytics (DMSO, kerosene, N-acetylcysteine), corticosteroids (prednisolone, dexamethasone) and immunomodulators (cell wall extracts of Mycobacterium phlei and Propionibacterium acnes).

Polishing of pretreated dye wastewater using novel sequencing batch reactors.

Novel, aerobic sequencing batch reactor technology was tested as a polishing step for anaerobically treated textile wastewater containing dye. Operation cycle times of 6, 8 and 12 hours were studied using discrete phase periods. The SBRs were able to further remove influent dye concentration of as little as 5 mg/L, and remove highly variable loadings of COD and SS to effluent levels of 100 and 20 mg/L respectively.

When to refer an infertile mare to a theriogenologist.

Most equine infertility cases can be solved with a methodical, thorough physical and reproductive examination and appropriate diagnostic laboratory aids. Repeated examinations may be needed in some cases to identify subtle anatomical abnormalities or irregularities between hormonal and physiological relationships of the reproductive tract. For pregnancy to occur, hormonal signaling must be exquisitely synchronized with physical changes of the reproductive tract and deposition of fertile semen in the uterus. Asynchrony of these events, infection, inflammation, previous trauma to the reproductive tract or "stress" can interfere with conception or maintenance of pregnancy. Infertile mares are presented for three common problems: (1) accumulation of intra-uterine fluid during or immediately after estrus; (2) long standing infection and/or chronic inflammation; or (3) irregular or no estrous cycles. By defining the problem, diagnostics can be chosen to determine the cause. Treatment protocols should be designed around the diagnosis and antibiotics, ecbolics or steroids should not be used indiscriminately. In all cases of mare infertility, semen quality needs to be determined to be satisfactory as a subfertile stallion bred to a subfertile mare greatly decreases the likelihood of pregnancy.

eFSH in clinical equine practice.

Equine follicle stimulating hormone (eFSH) has been used to induce follicular development in transitional mares and problem acyclic mares, as well as superovulate cycling mares. The most efficacious protocol is to administer 12.5 mg eFSH, intramuscularly, twice daily beginning 5 to 7 days after ovulation when the diameter of the largest follicle is 20 to 25 mm. Prostaglandins are to be administered on the second day of eFSH therapy. Treatment with eFSH is continued for 3 to 5 days until follicle(s) are >or=35 mm in diameter. The mare is subsequently allowed to 'coast' for 36 h, after which human chorionic gonadotropin is administered to induce ovulation.

Relationships between uterine culture, cytology and pregnancy rates in a Thoroughbred practice.

Endometrial cytology and culture specimens (n=2123) were collected concurrently with a guarded uterine culture instrument from 970 mares (738 barren, 1230 foaling and 155 maiden mares) during three breeding seasons (2001-2004). Results were compared to the 28-d pregnancy rate for the cycle from which the samples were taken. Cytological smears were evaluated for inflammation at x100 and graded as: not inflammatory (0-2 neutrophils/field), moderate inflammation (2-5 neutrophils/field), severe inflammation (>5 neutrophils/field), or hypocellular (scant epithelial cells and no neutrophils). Uterine culture swabs were plated within 6h, incubated for 72 h and results determined at 24, 48, and 72 h. Approximately, 20% (n=423) cytology samples were positive for inflammation (>2 neutrophils), whereas approximately 11% (n=231) of cultures had microorganisms recovered. A majority (64%) of the positive cultures (147/231) had inflammation on cytology smears. Streptococcus equi subsp. zooepidemicus was associated with more positive cytology results than coliforms (P<0.01). Mares with positive cytology or culture had lower pregnancy rates than mares with normal findings (P<0.01). Lowest pregnancy rates were recorded for mares with severe endometrial inflammation (21%, versus moderate inflammation 48%). Isolation of a microorganism from mares with endometrial inflammation was not associated with a further reduction in pregnancy rates. In barren, foaling and maiden mares, cytology was positive in 28, 17, and 5%, respectively, and culture was positive in 12.2, 11.1, and 3.2%. Foaling and maiden mares had higher pregnancy rates than barren mares (62, 69, and 44%, respectively, P<0.001). In conclusion, a positive cytology was twice as common as a positive culture, and isolation of microorganisms was associated with reduced pregnancy rates, even in the apparent absence of inflammation.

The effect of uterine torsion on mare and foal survival: a retrospective study, 1985--2005.

REASONS FOR PERFORMING STUDY: Anecdotal speculation suggests that prognosis for survival of mares and foals following correction of uterine torsion has improved over the past 30 years. OBJECTIVES: To determine statistically the outcome of uterine torsion according to duration of clinical signs, stage of gestation, parity, physical examination findings, method of correction, prognosis for survival and reproductive health of the mare, and prospects for the foal within the neonatal period. METHODS: This retrospective study combined cases from 4 equine referral hospitals. RESULTS: The stage of gestation at which uterine torsion occurred was a risk factor for survival of mare and foal. Overall mare survival was 53/63 (84%); when uterine torsion occurred at < 320 days gestation, 36/37 (97%) of mares survived compared to 17/26 (65%) survival rate when uterine torsion occurred at > or = 320 days gestation. Overall foal survival was 54% (29/54). When uterine torsion occurred at < 320 days gestation, 21/29 (72%) foals survived compared to 8/25 (32%) when uterine torsion occurred at > or = 320 days gestation. Thirty mares were discharged from the hospital carrying a viable fetus following uterine torsion correction and 25/30 (83%) of these mares delivered live foals that survived beyond the neonatal period. CONCLUSIONS: Prognosis for survival for mares and foals following uterine torsion is good and improves if torsion occurs < 320 days compared to > or = 320 days gestation. CLINICAL RELEVANCE: Gestational timing of uterine torsion should be considered when advising clients about the prognosis for survival of the mare and foal. The prognosis for a mare delivering a live foal is good if the mare is discharged from the hospital following uterine torsion correction with a viable fetus.

Continuous monitoring of penicillin G and gentamicin in allantoic fluid of pregnant pony mares by in vivo microdialysis.

REASONS FOR PERFORMING STUDY: Most current treatments for placentitis in mares are empirical with few control studies to evaluate their effectiveness. OBJECTIVE: To monitor drug concentrations in allantoic fluid of pregnant pony mares using in vivo microdialysis and establish if this method would be useful for determining allantoic concentrations of drugs in normal mares and those with placentitis. METHODS: Five late gestational pony mares had microdialysis probes inserted into the allantoic fluid using transabdominal ultrasound-guided allantocentesis. Single injections of penicillin G (22,000 u/kg), gentamicin (6.6 mg/kg bwt) and flunixin meglumine (1 mg/kg bwt) were administered i.v. and dialysate samples collected continuously for 24 h. In a separate study, drug concentrations were monitored in allantoic fluid of 2 mares with experimental placentitis induced by intracervical inoculation with Streptococcus equi ssp. zooepidemicus. Drug concentrations were measured by high performance liquid chromatography (penicillin G, flunixin meglumine) or enzyme-linked immunosorbent assay (gentamicin). RESULTS: Penicillin G and gentamicin achieved average peak concentrations of 9.8+/-2.2 and 8.5+/-3.1 microg/ml, respectively, in allantoic fluid of noninfected mares. Pharmacokinetic comparisons indicate that penicillin G persists much longer in allantoic fluid than blood, whereas gentamicin exhibited similar profiles in the 2 compartments. Flunixin meglumine was not detected in allantoic fluid. In infected mares, penicillin G achieved a similar peak concentration in allantoic fluid (11.2 microg/ml) whereas peak gentamicin concentration (3.9 microg/ml) appeared to be reduced relative to drug concentrations in noninfected mares. CONCLUSIONS: Microdialysis is a useful technique for continuous in vivo monitoring of drugs in equine allantoic fluid. Our results indicate that penicillin G and gentamicin undergo effective placental transfer in pregnant mares and in 2 mares that transplacental drug transfer may be altered selectively if active placental infection is present. POTENTIAL RELEVANCE: Further studies are needed to evaluate the feasibility of using increased dose intervals for penicillin G and an increased dose rate of gentamicin to effectively combat placental infections in mares.

Alteration in uterine contractility in mares with experimentally induced placentitis.

An experimental model of ascending placentitis was developed in the mare to characterize the uterine myoelectrical pattern in late gestation and determine how ascending placentitis altered this pattern. In experiment 1, myometrial electrical activity was analyzed during the early morning, late morning and evening hours in four mares in the last 15 days of gestation to identify patterns of activity. In experiment 2, nine mares received intra-cervical inoculations of Streptococcus equi subspecies zooepidemicus. Myoelectrical activity in the early morning and evening hours in these mares was compared with four control mares. In experiment 1, the number of spike burst clusters >30 s was greater in the evening than in the late morning hours (P < 0.04). Spike burst activity (number x duration) of mares in experiment 1 was similar during day and night recordings until the last 6 days of gestation when it gradually increased each evening until parturition (P < 0.05). In experiment 2, control mares experienced a gradual increase in the number of small spike burst clusters in the last 6 days (P = 0.008) and an increase in large and small spike burst clusters in the evening hours in the last 4 days of gestation (P = 0.03). Mares with experimentally induced placentitis never exhibited a rise in spike burst clusters but had an increase in the mean duration and activity index of large spike burst clusters in the 4 days before parturition (P < 0.04). In conclusion, control mares had a progressive, reversible rise in myoelectrical activity at night in the week preceding parturition. This was not observed in mares with experimentally induced placentitis. They exhibited an increase in the intensity and duration of large spike burst clusters possibly in response to local inflammation.

24-hour secretion patterns of plasma oestradiol 17beta in pony mares in late gestation.

The mare exhibits nocturnal uterine contractions in the last 6 days of gestation. It is hypothesized that estradiol 17beta (O17beta) may be associated with the nightly increase in uterine contractions. The 24-h secretion pattern of plasma O17beta was measured in 3 pony mares in late gestation to identify changes in release as the mare neared parturition. Blood was collected weekly at 08:00 hours beginning on day 240 and every third day from day 330 until delivery. Serial blood samples were collected from each mare every 30-min for 24-h beginning on gestation day 310 and every sixth day thereafter until parturition. Concentrations of O17beta were elevated at night with lowest concentrations occurring directly before sunset (p < 0.01). The natural log of the variance was increased at sunset (p < 0.01) and was decreased during the 6-h period immediately after sunrise. This pattern was especially evident in the 6 days that preceded parturition. The contrast between nocturnal and daytime concentrations of O17beta in the last 6 days of gestation may contribute to night-time delivery in the mare.

Mucus production by endometrium of reproductively healthy mares and mares with delayed uterine clearance.

The aims of this study were to compare various staining and fixation techniques for endometrial biopsy samples and, thus, to investigate the mucociliary apparatus in endometrium from reproductively healthy mares and mares with delayed uterine clearance. Endometrial samples were collected from the left and right uterine horns of reproductively healthy mares (n=5) and mares with delayed uterine clearance (n=4) during anoestrus, transition, oestrus and dioestrus. Each sample of endometrium was fixed in either Bouin's fixative or formalin, and stained with alcian blue (pH 1.0 or 2.5), periodic acid Schiff (alone and in combination with alcian blue) or mucicarmine. An extracellular mucus blanket was observed more frequently in tissue fixed in Bouin's fixative than in formalin-fixed tissue. Luminal epithelial cells and the extracellular mucus blanket were stained preferentially using alcian blue (pH 2.5). Ciliated cells were observed most readily in biopsy samples fixed with formalin and stained with either alcian blue (pH 2.5) or mucicarmine. Mucus production was increased in fibrotic nests and inflamed endometrial samples. According to image analysis, the amount of intracellular mucus increases during oestrus, but secretions become denser during dioestrus (P < 0.05). In the present study, mucus production in mares with delayed uterine clearance was greater than that of reproductively healthy mares (P < 0.05).

Interactions of xylazine and acepromazine with oxytocin and the effects of these interactions on intrauterine pressure in normal mares and mares with delayed uterine clearance.

The effects of the sedatives xylazine (predominantly alpha2 agonist) and acepromazine (predominantly alpha1 antagonist) and their influence on intrauterine pressure were measured in four reproductively normal mares and four mares with delayed uterine clearance. Intrauterine pressure was measured in each mare during oestrus for three 100 min periods using an 8-F catheter with three discrete pressure sensors. After 10 min of baseline recording, xylazine, acepromazine or saline was administered i.v. Oxytocin was administered i.v. after a further 30 min, and pressure recordings were continued for 60 min. The pressure changes analysed were: number of uterine contractions; time of onset and duration of the first contraction; and the time at which intrauterine pressure changed from baseline. Data were analysed using the mixed procedure of the Statistical Analysis System. ANOVA detected an effect of treatment (P < 0.0001) and a treatment by group interaction (P < 0.001). Xylazine administration caused a tetanic contraction in all mares. When mares with delayed uterine clearance were sedated with xylazine before administration of oxytocin, the duration of increased intrauterine pressure was longer than that of normal mares (24.87 +/- 2.52 and 15.81 +/- 2.46, respectively; P < 0.0001). Acepromazine administration had no effect on the oxytocin-induced contraction pattern in normal mares, but there was a decrease in the number of contractions in mares with delayed uterine clearance. The enhanced response to alpha-agonists and -antagonists observed in mares with delayed uterine clearance when the drugs were administered before oxytocin may be due to denervation supersensitivity. After mating, sedation of mares with xylazine is preferred to sedation with acepromazine, as xylazine increases uterine contraction time.

Dynamics of prostaglandin secretion, intrauterine fluid and uterine clearance in reproductively normal mares and mares with delayed uterine clearance.

Two experiments were performed to investigate relationships between oxytocin, prostaglandin release, uterine emptying and fluid accumulation in the uterus. In Experiment 1, the effect of oxytocin on the pattern of prostaglandin release during uterine clearance of radiocolloid was measured in 5 normal mares and 5 mares with delayed uterine clearance. Uterine clearance was measured during estrus by scintigraphy at 0, 60 and 120 min after colloid infusion. After the 120-min reading, 20 IU, i.v., oxytocin were given, and the amount of colloid cleared was measured at 135, 150 and 180 min. Plasma was obtained prior to and during scintigraphy at 5- and 15-min intervals to measure concentrations of 15-keto-13,14-dihydro-PGF2 alpha metabolite (PGFM) by RIA. In Experiment 2, plasma PGFM levels were compared after administration of oxytocin in 8 normal mares and 6 mares with delayed uterine clearance to determine if intrauterine fluid stimulated prostaglandin release. Mares received 2 treatments in a cross-over design. Treatment 1 consisted of 20 IU, i.v., oxytocin during estrus. Treatment 2 consisted of an infusion of 10 mL, i.u., saline 15 min prior to oxytocin administration. Treatments were performed 4 to 6 h apart. Blood was collected and PGFM was measured as in experiment 1. Data were analyzed by least squares analysis of variance. In Experiment 1, regression analysis of scintigraphy and PGFM profiles indicated that time response curves differed between groups (P < 0.01). At 120 min, normal mares retained 40.4 +/- 4.9% (mean +/- SEM) of the radiocolloid while mares with delayed clearance retained 88 +/- 5%. Fifteen minutes after oxytocin administration (135 min), all normal mares and 4 of 5 mares with delayed clearance retained only < 6% of the colloid. During the first 120 min, plasma PGFM concentrations did not differ between the 2 groups. After oxytocin was given, plasma PGFM concentrations increased in 4 of 5 mares with delayed uterine clearance (80 to 3,096 pg/mL) but not in normal mares (13 to 46 pg/mL). In Experiment 2, plasma PGFM concentrations did not rise in normal mares but rose in 3 of 6 mares with delayed clearance (135 to 483 pg/mL) independent of treatment or period. The results suggest that intrauterine clearance of radiocolloid after oxytocin administration appears to be independent of PGF2 alpha release in normal mares during estrus. The difference in prostaglandin release response after oxytocin administration between the 2 groups was unrelated to the presence of intrauterine fluid.

Changes in intrauterine pressure after oxytocin administration in reproductively normal mares and in those with a delay in uterine clearance.

Intrauterine pressure was measured in 4 reproductively normal mares and 4 mares with delay in uterine clearance after administration of oxytocin to determine if intrauterine pressure varied between dosage and group. Changes in intrauterine pressure were measured during estrus, when a follicle was > or =35 mm, using a Millar "Mikro-tip" catheter that had 3 discrete pressure sensors/channels. Mares received 4 different treatments of 10, 5, 2.5 or 0 IU (vehicle) of oxytocin. The protocol for each treatment consisted of a 10-min baseline recording, administration of treatment and measurement of changes in intrauterine pressure for 65 min. After administration of the first two treatments, mares were rested for 2 h and the protocol repeated for the remaining 2 treatments. Changes in intrauterine pressure were measured on a physiograph and stored in a computer. The results were analyzed by 4x4 Latin Square Design analysis of variance (ANOVA) using the GLM procedure of the Statistical Analysis System. The ANOVA detected a main effect of treatment (P<0.01) and mare (nested within group; P<0.01) but no effect of channels, group or treatment-by-group interaction. There was a dose-dependent increase in uterine activity in both normal mares and those with delayed uterine clearance. A dose of 10 IU of oxytocin induced a larger number of uterine contractions (5.67+/-0.06) for a longer time (24.09+/-1.18 min) than the 5 IU (4.16+/-0.06 contractions and 16.31+/-1.18; P<0.01 min) or 2.5 IU dose (4.08+/-0.06 contractions and 17.61+/-1.18 min). The first intrauterine wave occurred most often near the tip of the horn in 10 of 12 recordings in normal mares and in 8 of 12 recordings in mares with delayed uterine clearance. It was then propagated from the middle of the horn to the uterine body just cranial to the cervix. There was no pattern of propagation for subsequent intrauterine pressure waves. We conclude that the difference in spontaneous clearance of the uterus between the 2 groups is not reflected in their response to exogenous oxytocin as determined by changes in intrauterine pressure.