Clinical evaluation of the use of aglepristone, with or without cloprostenol, to treat cystic endometrial hyperplasia-pyometra complex in bitches

The aim of the study was to evaluate the efficacy of aglepristone (10 mg/kg on days 1, 2 and 8) for the treatment of metritis or pyometra in bitches (n = 67) either alone for cases of metritis (n = 15), or in cases of pyometra (n = 52) with (n = 32) or without (n = 20) the addition of low doses (1 microg/kg) of cloprostenol for 5 days (days 3-7). Examinations performed on day 90, in addition to days 8, 14 and 28, determined that treatments had been curative in the long term in 54/67 bitches (80.6%). Bitches in whom pyometra did not resolve, were given additional aglepristone on day 14 (n = 38) and day 28 (n = 20). Aglepristone alone was curative in 15/15 bitches with metritis. In 17/17 bitches with closed pyometra, cervical opening occurred within 48 h of aglepristone administration. Amongst the 52 bitches with open (n = 35) or closed (n = 17) pyometra, the additional treatment with cloprostenol from days 3 to 7, significantly improved the overall success rate at day 90, which was 27/32 (84.4%), compared to 12/20 (60.0%) in bitches without cloprostenol (P < 0.05). The leucocyte count and plasma progesterone concentrations significantly decreased over the course of treatment. Thirteen of 15 bitches in whom plasma progesterone concentrations were initially low (< 3.18 nmol/L) were cured. The recurrence rate after 12 and 24 months was 13.0% (3/23) and 19.0% (4/21), respectively.     

The induction of parturition in the bitch using sodium cloprostenol

The objectives of this studies were to determine a continuous low-dose treatment regimen for the administration of sodium cloprostenol to the bitch that did not cause polydipsia, and whether this treatment would induce normal and timed parturition in bitches during late pregnancy. Non-pregnant greyhound bitches (n=18) received sodium cloprostenol subcutaneously, via a miniosmotic pump, at dose rates of 0.875 to 4.5 microg/kg/24 h, for 7 days (Days 0 to 7). Daily water intake was measured from Day -2 to Day 9. Polydipsia was observed in bitches treated with the higher dose rates but not in bitches treated with the lowest dose rate of 0.875 microg/kg/24 h. In the second experiment, pregnant greyhound bitches received sodium cloprostenol at dose rates of 1 (n=4), 2 (n=1) and 3 microg/kg/24 h (n=1), on Day 57 of pregnancy. Polydipsia was observed in bitches treated at the higher dose rates of 2 and 3 microg/kg/24 h, but not in the bitches treated at the lower dose rate of 1 microg/kg/24 h. These treatments resulted in the successful induction of parturition. Parturition was associated with a decrease in plasma progesterone concentrations, a reduction in body temperature, and an increase in plasma concentrations of 13,14-dihydro-15-keto prostaglandin F2alpha. The first puppy was born 37.7 +/- 2.9 h after the start of treatment (range 28 to 46 h). The duration of whelping was approximately 15.7 +/- 2.2 h (range 10 to 24 h). The litter size was 9.2 +/- 0.8 pups (range 6 to 12 pups), and the puppy survival rate was 6.0 +/- 0.8 per litter (range 4 to 9 pups). This study demonstrated that the administration of sodium cloprostenol in continuous low dose for 24 h is an effective treatment for the induction of parturition in bitches during late pregnancy. This treatment resulted in the birth of healthy pups, with minimal or no side effects to the bitch.     

A model for cystic endometrial hyperplasia/pyometra complex in the bitch

The objective of this study was to develop a reliable model for the study of the cystic endometrial hyperplasia and pyometra complex (CEH/P) in the bitch. Greyhound bitches (n = 15) were ovariectomised and allocated into three groups (Group 1, n = 5; Group 2, n = 5; Group 3, n = 10, including 5 used from Group 1). Simulated proestrus, estrus and diestrus were induced by treatment with estradiol benzoate and megestrol acetate. The duration of cervical opening during estrus was determined by the intra-vaginal infusion of radio-opaque medium and subsequent radiography of the uterus (Group 1). One milliliter of a culture of Escherichia coli (with five uro-pathogenic virulence factors as identified by PCR: pap, sfa, hlyA, cnf1 and fim) was inoculated intra-vaginally daily throughout the simulated estrus (Group 2). One milliliter of the culture (n = 6) or sterile Luria-Bertani broth (n = 4) was introduced directly into the uterus on simulated diestrus Days 8 or 12 (Group 3). Necropsies were performed 12 and 7-14 days after the inoculation (Groups 2 and 3). The cervix remained open throughout the duration of simulated estrus (5-6 days) in four out of five bitches, and for a shorter duration (3 days of a 6-day estrus period) in one bitch (Group 1). CEH/P was induced by inoculation of bacteria into the uterus (10/10 bitches) but not into the vagina (0/5 bitches), (P = 0.003). A model for the study of CEH/P has been validated.     

Sodium cloprostenol administered at a continuous low dosage induces polydipsia and suppresses luteal function in early dioestrous bitches.

The aim of this study was to determine whether sodium cloprostenol administered at a continuous low dosage induced luteolysis and polydipsia in early dioestrous bitches. Sodium cloprostenol was administered subcutaneously to greyhounds at doses of 4.04-5.19 microg/kg/day (treated group, n=5) or 0 microg/kg/day (control group, n=5) delivered by mini-osmotic pumps for 7 days. The treated bitches and two of the control bitches were in early dioestrus (Days 5-14, and 6 and 10, respectively) when the mini-osmotic pump was inserted (Day 0). Concentrations of plasmatic progesterone were measured in dioestrous bitches each day from Day -2 to 7, and then weekly until Day 90. Daily intake of water was ascertained in all bitches from Day -2 until Day 10, and their weight was measured on Days -2, 6 and 13. Biochemical analyses on plasma for concentrations of urea and glucose, and urinalyses were performed on all bitches before (Day -1), during (Day 4) and after treatment (Day 10). Concentrations of plasmatic progesterone declined dramatically and rapidly in treated bitches after Day 0 to <2.9 ng/ml but were not similarly affected in the dioestrous control bitches. However, in three of five treated bitches, concentrations of plasmatic progesterone increased to >1 ng/ml in the period from Day 10 to 90 indicating that luteolysis was incomplete. All treated bitches were polydipsic (intake of water >100 ml/kg/day) for 2-6 days during the period of treatment, and for 0-2 days immediately after treatment (Days 7 and 8). One control bitch was polydipsic on Days -2, -1 and 0. The treated bitches were also polyuric since they were hyposthenuric (<1.007, n=4) or isothenuric (1.010, n=1) on Day 4, their weight did not increase and no gastrointestinal or respiratory effects were observed. The control bitches were always hypersthenuric when measured during and after treatment (>1.021). Biochemical analyses of plasma and other data obtained from urinalyses did not reveal any differences between groups. This study indicated that sodium cloprostenol administered at a continuous low dosage induced polydipsia and suppressed luteal function in early dioestrous bitches.     

Selective control of the estrous cycle of the dog through suppression of estrus and reduction of the length of anestrus

The objective of this study was to determine the effectiveness of testosterone in suppressing estrus in the bitch, and of cabergoline in shortening the length of the subsequent anestrous period. In Experiment 1, 12 diestrual Beagle bitches were randomly divided into two groups when plasma progesterone (P(4)) concentration was <1 ng/ml (Day 0). Starting on Day 0, bitches in Group 1 (n=6) were treated with testosterone cypionate every 14 days for a total of 239 days, and bitches in Group 2 served as untreated controls. On Day 274, bitches in both groups were treated with cabergoline for 40 days and blood samples were obtained on Days 274, 276 and 279 for determination of plasma prolactin (PRL) concentrations using RIA. All bitches were observed for proestrual bleeding during treatment with cabergoline. In Experiment 2, 12 Greyhound bitches previously treated with testosterone within the last 6 months were randomly divided into two groups. At the initiation of this experiment, P(4) concentration was determined to verify that all bitches had a concentration of <1 ng/ml (Day 0). Starting on Day 0, bitches in Group 1 (n=6) were treated with cabergoline for 36 days, and bitches in Group 2 (n=6) served as untreated controls. Blood samples were obtained on Days 0, 2 and 5 to determine PRL concentrations. All bitches were observed for proestrual bleeding during treatment with cabergoline. In Experiment 1, one bitch (Group 1) exhibited estrus after treatment with testosterone (1mg/kg body weight) for 43 days, and one bitch (Group 1) exhibited estrus after treatment with testosterone (2mg/kg body weight) for 113 days. None of the other four bitches in Group 1 exhibited estrus during the period of testosterone treatment (239 days). All bitches in Group 2 (control) exhibited estrus during the 239 days of the study. In addition, five of the six testosterone-treated bitches showed signs of proestrual bleeding within an average of 12.6 days (range of 5-25 days) after treatment with cabergoline; and, four of the six nontestosterone bitches showed signs of proestrual bleeding within an average of 28 days (range of 6-46 days). Prolactin concentrations in bitches in both Groups 1 and 2 significantly decreased after treatment with cabergoline. In Experiment 2, one of the six bitches showed signs of proestrual bleeding within 15 days after treatment with cabergoline. From the results of this study, it was concluded that exogenous testosterone was moderately effective (66%) in suppressing estrus in Beagle bitches, and cabergoline was effective in shortening the length of the anestrous period of Beagle bitches whose estrous cycle was previously suppressed with exogenous testosterone, but less effective in shortening the length of the anestrous period in Greyhound bitches previously treated with testosterone to suppress estrus.     

The intravaginal application of misoprostol improves induction of abortion with aglepristone

The aim of the present study was to compare the clinical and endocrinological effects of four different treatments for the induction of abortion in bitches. For this purpose, 28 pregnant bitches between days 25 and 35 of gestation, were randomly assigned to four groups. In group I (n = 7), only aglepristone (AGL, 10mg/kg bw, two injections 24 h apart, s.c.) was administered. In group II (n = 7), AGL (as in group I), cabergolin (CAB, 5 μg/kg, daily p.o., until completion of abortion) and misoprostol (MIS, 200 μg for bitches with ≤ 20 kg bw, 400 μg for bitches with > 20 kg bw, daily intravaginally, until completion of abortion) were administered. In group III (n = 7), AGL (as in group I) and MIS (as in group II) were administered. In group IV (n = 7) AGL, (as in group I) and cloprostenol (CLO, 1μg/kg bw, s.c., two injections 24 h apart with the AGL injections) were combined. In all groups, bitches were examined daily, clinically and ultrasonographically to monitor resorptions/abortions. To measure serum progesterone (P4) and total estrogen (TE) concentrations, blood samples were collected in all groups immediately after the first AGL administration and every other day until completion of abortion. No statistical differences were found between groups concerning the duration until completion of abortion following treatment (n.s.); however, in Group III, 6 d after the start of treatment all pregnancies were terminated whereas in Group I, II and IV, only 57.1% (4/7), 85.7 % (6/7) and 42.8 % (3/7) of pregnancies were terminated. In the latter groups, all pregnancies were terminated between days 8 and 10 after the start of treatment. In Group IV, P4 concentrations on days two and one before the beginning of abortion and the day the abortion started was significantly lower than in the other groups (P < 0.01). No statistical differences were found between groups for TE concentrations (P > 0.05). In Groups I, II and III, no severe side effects occurred. Severe vomiting after each treatment and until the end of abortion was observed in Group IV only. In conclusion, only when a combination of AGL and MIS was used abortion was completed within 6 d in all bitches whereas the additional use of CAB did not improve the treatment.     

Reproductive performance of dairy cows following treatment with cloprostenol 26 and/or 40 days postpartum: a field trial

One hundred and seventy Holstein Friesian cows were randomly assigned to receive either 500 ug cloprostenol or saline placebo on Day 26 postpartum followed by 500 ug cloprostenol or saline on Day 40 postpartum. Four treatment groups were formed: Group 1 - saline (Day 26)/saline (Day 40); Group 2 - cloprostenol/(Day 26) saline (Day 40); Group 3 - saline (Day 26)/cloprostenol (Day 40); Group 4 - cloprostenol (Day 26)/cloprostenol (Day 40). Double blind techniques were used in administering treatments and in assessing the response to treatment. Palpation of the reproductive tract per tectum and uterine biopsies were performed on 92 cows prior to each treatment at Day 26 and Day 40 postpartum. Progesterone concentrations were determined on milk samples collected prior to treatment. There were no significant differences among treatment groups with respect to services per conception, number of heats detected before first service and culling for infertility. Cloprostenol treatment at Day 26 appeared to delay the first estrus, but it reduced the number of days to conception after the first service. Cows receiving cloprostenol at Days 26 and/or 40 had a decreased calving-to-conception interval compared to controls (P = 0.01). Sequential therapy with two doses of cloprostenol resulted in slightly better reproductive performance than either treatment on Day 26 or 40 alone. Treatment with cloprostenol resulted in a decrease in the subsequent incidence of pyometra (P < 0.05). It is concluded that in the herd studied, cloprostenol therapy at Day 26 and/or 40 postpartum was beneficial to reproductive performance. Although it was anticipated that cloprostenol would be more effective in cows with elevated progesterone levels, the opposite was observed at the Day 26 cloprostenol treatment. Uterine biopsy at Days 26 and/or 40 had a detrimental effect on subsequent reproductive performance.     

Clinical evaluation of different applications of misoprostol and aglepristone for induction of abortion in bitches

The aim of the present study was to compare the clinical and endocrinological effects of different applications of misoprostol (MIS) and aglepristone (AGL) for the induction of abortion in bitches. For this purpose, 28 healthy pregnant bitches from different breeds, ages, body weights (Body weigt, BWs, 10–40 kg), and between Days 25 to 35 of gestation were used. Bitches were randomly assigned to four groups. In group 1 (GI, n = 7), AGL (10 mg/kg BW, s.c. on 2 consecutive days); in group 2 (GII, n = 7), AGL (as in GI), intravaginal MIS (IVag, 200 μg for bitches with ≤20 kg BW, 400 μg for bitches with >20 kg BW, daily intravaginally until completion of abortion); in group 3 (GIII, n = 7), AGL (as in GI), ICVag (as in GII), per os MIS (400 μg for bitches with ≤20 kg BW, 800 μg for bitches with >20 kg BW, daily orally, until completion of abortion); in group 4 (GIV, n = 7), AGL (as in GI), per os MIS (as GIII) were used. Clinical, vaginal, and ultrasonographic examinations were performed daily until abortion was completed. For measurement of serum progesterone, blood samples were collected in all groups immediately after the first AGL administration and every other day until completion of abortion. No statistical differences were found between groups concerning the duration until completion of abortion after treatment (nonsignificant); however, in GII, one bitch completed abortion 2 days after the start of treatment.     

Ovulation induction in anestrous bitches by pulsatile administration of gonadotropin-releasing hormone

Preliminary studies in anestrous Beagle bitches demonstrated that a single injection of gonadotropin-releasing hormone (150 micrograms) produced a rapid, physiological rise in serum estradiol lasting 1-3 days while progesterone remained below 1 ng/ml, whereas serial injections of FSH rapidly produced greater elevations in estradiol and a rapid rise in progesterone over 2 ng/ml. Consequently, attempts to induce fertile ovulation by means of pulsatile intravenous administration of GnRH (1 pulse/1.5 hours for 6-12 days; 0.04-0.43 micrograms/kg body weight/pulse) were conducted in eight anestrous bitches. Willingness to mate, serum progesterone levels and results of mating were monitored. In six of the eight bitches, vulval and vaginal signs of proestrus occurred by Day 2-4 after initiation of treatment (Day 0); but, two bitches showed negligible responses. In five of the six bitches in which proestrus was induced, behavioral (n = 4) and vaginal (n = 5) correlates of early estrus occurred by Day 5-7 of treatment and breedings occurred over a period of 4-12 days. Following onset of estrus, four of the five bitches had increases in serum progesterone levels between Days 14 and 18 after initiation of treatment (and 4-11 days after cessation of treatment); three of them became pregnant and whelped normal litters (ranging from 9 to 11 pups). The fifth bitch did not have elevated progesterone during the induced estrus, and upon return to estrus one month later was successfully bred and whelped a normal litter of 10 pups.(ABSTRACT TRUNCATED AT 250 WORDS)     

Combination dopamine agonist and prostaglandin agonist treatment of cystic endometrial hyperplasia-pyometra complex in the bitch

Cystic endometrial hyperplasia-pyometra (CEH-P) complex is a progesterone-dependent disease that requires medical treatment in bitches intended for breeding. To test the efficacy and safety of a combined protocol and to assess the effect of age, stage of cycle, previous steroid hormone administration and parity on treatment, 29 bitches diagnosed with CEH-P complex were treated daily with cabergoline 5 microg/kg PO and cloprostenol 1 microg/kg SC for 7-14 days, along with supportive antibiotic and hydration therapies. Before treatment, and on Days 3, 7 and 14, all bitches were evaluated clinically and uterine horn diameter measured during trans-abdominal ultrasonography. Twenty-four of 29 bitches were cured by either Day 7 or 14. Nine bitches had mild digestive side effects. Clinical signs related to pyometra began to improve markedly as early as Day 2 of treatment. Uterine diameters decreased (P < 0.05) by Day 3 of treatment, and continued to gradually decrease, reaching normal size by Day 14. Relapses occurred in 6 of 29 cases. Pregnancy was achieved in one of the two young bitches bred after treatment. No significant relationships were found between success rate and age, stage of the estrous cycle, previous hormone administration or parity. Although no variables affecting treatment results could be identified, this combination of compounds was found to be an efficient and safe for treatment of CEH-P.     

Reproductive performance of dairy cows following treatment with fenprostalene, dinoprost, or cloprostenol between 24 and 31 Days post partum: a field trial

Three hundred and one Holstein cows (n=301), calving at a commercial free-stall dairy farm, were randomly assigned to 1 of 3 prostaglandin treatment groups or a placebo group. The placebos were packaged 3 ways to mimic the 3 commercial prostaglandin preparations. Group 1 received 1 mg fenprostalene and 1.6 mg oxytetracycline; Group 2 received the fenprostalene placebo (2 ml polyethylene glycol and 1.6 mg oxytetracycline); while Group 3 was given 25 mg dinoprost. Group 4, the dinoprost placebo received 5 ml saline; Group 5 received 500 ug cloprostenol; and Group 6 the cloprostenol placebo received 2 ml saline. The treatments were administered between Days 24 and 31 post partum. Double blind techniques were used in administering treatments and in assessing the response to treatment. There were no significant differences among treatment groups with respect to incidence of retained fetal membranes, endometritis, pyometra, anestrus, number of services per pregnancy, calving-to-first estrus interval, services per conception, number of prostaglandin treatments other than those administered between Days 24 and 31 post partum, the percentage culled for reproductive reasons and all factors combined. Cows receiving fenprostalene, dinoprost or cloprostenol had a decreased calving-to-conception interval compared with that of the controls (P = 0.05). It is concluded that, in the herd studied, treatment with any of the 3 commercially available prostaglandin products between Days 24 and 31 post partum was beneficial for reproductive performance.     

In vitro comparison of myometrial contractility induced by aglepristone-oxytocin and aglepristone-PGF2alpha combinations at different stages of the estrus cycle in the bitch

The aim of this in vitro study was to compare the uterokinetic activity of oxytocin and dinoprost, the natural PGF2α, with or without aglepristone, in canine myometrial fibers. Thirty-three bitches were allocated into one of four groups, depending on their estrous stage and whether or not they had received a treatment with aglepristone (metestrus aglepristone, n = 5; metestrus without treatment, n = 9; anestrus aglepristone, n = 9; anestrus without treatment, n = 10). After hysterectomy, longitudinal and circular uterine strips were mounted in organ baths. Oxytocin or PGF2α (10 nmol/l to 10 micromol/l) were applied non-cumulatively. A linear mixed effects models theory was used to compare the fiber effect, the aglepristone effect, and the treatment effect, from the area under the curves calculated from the contractile effect/concentration curves for each drug.Oxytocin and PGF2α induced concentration-dependent myometrial contractions in longitudinal (LF) and circular myometrial fibers (CF), indicating the presence of functional contractile oxytocin- and PGF2α-receptors in metestrus and anestrus.The contractile response to oxytocin was greater in LF than in CF in all of the groups; the response to PGF2α was greater in LF than in CF in non-treated bitches in anestrus and in treated bitches in metestrus. These results suggest that there is a difference in sensitivity or a heterogeneous distribution of oxytocin and PGF2α-receptors in the myometrial layers, which is independent of hormonal impregnation.The contractile response to oxytocin and PGF2α was significantly increased after aglepristone treatment in LF during metestrus, suggesting that the progesterone withdrawal induced by aglepristone has a role to play. The longitudinal myometrial layer also appeared to be the target for the two drugs at this stage.This study provides new information about canine uterine contractile activity, notably the differing behavior of myometrial CF and LF; in vivo studies are required to test the use of a combination of aglepristone and oxytocin in the treatment of canine pyometra.     

Serum androstenedione and testosterone concentrations during pregnancy and nonpregnant cycles in dogs

Concentrations of testosterone and of androstenedione were determined by radioimmunoassay in serum samples collected every 2-5 days throughout the periovulatory and luteal phases of the ovarian cycles of pregnant and nonpregnant beagle bitches. Testosterone levels were consistently lower than those of androstenedione, reached peaks of 29 +/- 4 ng/dl near the time of the preovulatory luteinizing hormone peak, and were reduced to near the limits of detection (less than or equal to 5-10 ng/dl) throughout the luteal phase. Androstenedione levels reached preovulatory peaks of 73 +/- 13 ng/dl, were 54 +/- 7 ng/ml during early estrus, increased (P less than 0.05) to early luteal phase peaks of 76 +/- 8 ng/dl between Days 6 and 18, and then declined to 41 +/- 5 ng/dl by Day 35-40 in both pregnant (n = 8) and nonpregnant (n = 4) bitches. Subsequent protracted increases in androstenedione occurred in 4 of 8 pregnancies but in none of the nonpregnant bitches. From Days 42 to 64 the differences in mean levels between pregnant (45 +/- 2 ng/ml) and nonpregnant (32 +/- 3 ng/ml) bitches was not significant (P greater than 0.05). At parturition androstenedione levels fell (P less than 0.05) abruptly from 39 +/- 7 to 13 +/- 3 ng/dl. These results suggest that, in the bitch, androstenedione is the major circulating androgen during the follicular and luteal phases and that patterns of androstenedione levels during the luteal phase parallel those reported for progesterone in pregnant and nonpregnant bitches, including maintenance of elevated levels throughout gestation and an abrupt decline at parturition.     

A retrospective study of bitches with pyometra,medically treated with aglepristone

Pyometra is a common and life-threatening disease of intact bitches caused by hormonal influence of the uterus in combination with bacterial infection. The treatment of choice is ovariohysterectomy, but several purely medical options are available. Common drugs used for medical treatment in combination with antimicrobials are progesterone receptor blockers, prostaglandins, and dopamine agonists. The aim of this study was to evaluate long-term recovery and fertility after treatment with the progesterone receptor blocker aglepristone in bitches with pyometra. Data from 28 bitches with pyometra, admitted to the University Animal Hospital, Swedish University of Agricultural Sciences, during a 9-year period, were studied retrospectively and followed up by telephone interviews with the owners. The bitches had been treated with aglepristone at a dose of 10 mg/kg on a median of four occasions. All bitches had also been treated with antimicrobial drugs for a mean duration of 23 days, the most frequently used being enrofloxacin. Escherichia coli were the most commonly isolated bacteria from cranial vagina. The outcome was assessed for up to 6 years after treatment. The success rate, determined as restored clinically healthy status, was 75% (21/28 bitches), and the recurrence rate of disease was 48% (10/21 bitches). The mean time until recurrence was 10.5 months after the end of treatment. After treatment, 69% (9/13) of the mated bitches produced puppies. Of the seven bitches that did not have a successful treatment, six were ovariohysterectomized and one was euthanized. In conclusion, medical treatment with aglepristone in combination with antimicrobial therapy was successful in 75% of the bitches studied and the recurrence rate was 48%.     

Induction of canine pyometra by inoculation of Escherichia coli into the uterus and its relationship to reproductive features

To characterize oestrus-related factors affecting the induction of and recovery from pyometra in bitches, 60 clinically healthy beagle bitches were used for induction of pyometra by inoculation of Escherichia coli into the uterus during oestrous and metoestrous stages. The animals were classified into the following six groups according to inoculation time: Days 1-10, 11-20, 21-30, 31-40, 41-50 and 51-60 after LH surge. The incidence of pyometra during the periods Days 11-20 and 21-30 after LH surge was 90.9% and 78.9% respectively, while that during Days 1-10 and 51-60 after LH surge was less than 20%, and the patterns of the incidence of pyometra and the serum progesterone levels were similar. There was no difference in the incidence of pyometra induced in bitches less than 5 years old compared to bitches over 6 years old. Oestrus in all of the bitches with pyometra induced by E. coli returned with or without PGF 2alpha treatment, unlike in bitches with spontaneous pyometra. The duration of the oestrous cycle in the non-treated and PGF 2alpha-treated groups was 231.4+/-55.2 days and 162.1+/-40.6 days (P < 0.001), respectively, and there was no difference in the rate of return of oestrus between the two groups. The conception rate in all of the bitches in which oestrus had returned was 81.8%. The above findings indicate that the period during which severe pyometra could be induced was limited to the early stage in metoestrus.     

Mucometra, cystic endometrial hyperplasia, and pyometra in the bitch: advances in treatment and assessment of future reproductive success

Pyometra is a common reproductive disorder which affects nearly one fourth of all female dogs before they reach 10 y of age. An association between pyometra and the most common uterine disease of the bitch, cystic endometrial hyperplasia, has been established, as the latter allows commensal bacteria originating from the vagina to proliferate in the uterus at the end of estrus. The progressive degenerative process in the development of cystic endometrial hyperplasia is usually proposed as the initiating lesion for pyometra in bitches; this is mediated by progesterone and potentially aggravated by estrogens. However, a separate process caused by local uterine irritation to trophoblastic reaction and bacterial proliferation has been recently proposed as an alternate mechanism leading to the development of pyometra. Pyometra is clinically distinct in pathogenesis, signs, treatment and prognosis from postpartum metritis or mucometra. Treatment of pyometra has historically involved ovariohysterectomy, however, during the last 10 y, numerous effective treatments have been proposed to treat both open and closed cervix pyometra with good success and future fertility. Among the treatments available, the use of repeated low doses of prostaglandins alone or in association with either dopamine agonists or progesterone-receptor antagonists has been demonstrated to be a viable alternative for valuable breeding dogs.     

Prostaglandin F2α induced luteolysis,hypothermia, and abortions in beagle bitches

Luteal phase plasma progesterone was radioimmunoassayed in samples collected before, during, and after a 72 hr treatment period during which Beagle bitches received repeated i.m. injections of prostaglandin F₂α (n=17) or saline (n=3). PGF₂α (20 ug/kg every 8 hr or 30 ug/kg every 12 hr) was administered to 7 pregnant and 8 nonpregnant bitches during the mid or late luteal phase of the cycle (Day 25–58) and to 2 nonpregnant bitches during the early luteal phase (Days 5 and 20). Progesterone was depressed from pretreatment levels (3 – 40 ng/ml) in each of the 15 bitches given PGF₂α after Day 25 of the cycle. Mean progesterone (ng/ml plasma) at ?24, 0, 12, 24, 36, 48, 60, 72 and 96 hr from the initial PGF₂α injection were 16.6, 15.6, 9.3, 5.1, 2.1, 1.5, 1.4, 1.1 and 1.1 (±0.9, n=15). Thereafter, progesterone was nondetectable in the 8 nonpregnant bitches and in 4 pregnant bitches that aborted. Abortions occurred when progesterone was depressed to 0.6 – 1.4 ng/ml, 56–80 hr after starting PGF₂α treatment on Days 33–53 of the cycle. Three pregnant bitches did not abort when progesterone was depressed to a mean low value of 2.1 ng/ml during PGF₂α treatments begun on Day 31 – 40 of pregnancy. Progesterone in these bitches recovered to 5 – 10 ng/ml and was maintained until the normal prepartum decline. Since PGF₂α can induce complete luteolysis it may be of use as an abortifacient in the bitch.A transient fall in rectal temperature occurred in each of 12 luteal phase bitches injected with PGF₂α (20 ug/kg, i.m.). The hypothermia was detectable within 15 min, maximal at 45 – 60 min, and averaged 1.39° C. No temperature changes were noted in eight ovariectomized bitches similarly treated. In six luteal phase bitches, plasma progesterone fell 20–45% within the 15 min required to observe a consistent decline in rectal temperature following PGF₂α administration. The transient hypothermia following PGF₂α appears to be secondary to the luteolytic effect and dependent on a fall in progesterone.     

Recovery, morphological quality, and in vitro maturation of follicular oocytes from bitches with pyometra

The objective of this study was to collect oocytes from ovaries of bitches with pyometra and to characterize the quality of the oocytes recovered. In 10 of 12 cases of pyometra, follicles with a diameter of 500 microm to 1mm were observed in the ovaries. A total of 710 oocytes were collected from 10 bitches by puncturing individual follicles after slicing the ovarian tissues. Oocyte recovery was successful from a bitch with severe clinical signs of pyometra. Of the oocytes collected, 53.5% were surrounded by > or =2 layers of cumulus cells, and 55.0% of these cumulus-oocyte complexes (COCs) had a darkly pigmented ooplasm >110 microm in diameter (large-dark COCs). The number of large-dark COCs per bitch varied from 1 to 72. A germinal vesicle with fine filaments of chromatin (Type A) was observed in 51.8% (range 21.1-100%) of the oocytes of large-dark COCs. Out of 50 oocytes cultured for 72 h, 6.0% developed to Metaphase II. In conclusion, there were many follicles with a diameter of 500 microm to 1mm in ovaries of bitches with pyometra, and many oocytes recovered from these follicles underwent meiotic maturation in vitro. The number of oocytes and COCs, and the morphological quality of the germinal vesicles varied among individual bitches.     

Decrease of body temperature after aglepristone treatment in bitches

Body temperature responses and the timing of abortions were evaluated in pregnant bitches with the anti-progestin aglepristone. Fifteen purebred and crossbred, 25-45 days pregnant, were included in this study and seven untreated bitches at the same stage of pregnancy served as controls. Treated bitches were administered two applications of aglepristone (10 mg/kg SC) 24 h apart for pregnancy termination. Pregnancy termination was confirmed by ultrasonographic assessment. Body temperature was rectally measured three times a day for 6 days beginning 24 h before treatment or pregnancy diagnosis in the treated and control bitches, respectively. Additionally, serum progesterone concentrations were assessed at time points during the study in the treated bitches. Pregnancy was terminated in 14 treated bitches in a mean+/-S.E.M. of 4.3+/-0.7 days after treatment. Control bitches remained pregnant. In the treated bitches, but not in the controls, body temperature significantly decreased 24 h after the beginning of the treatments (P < 0.01) and then gradually returned to pre-treatment values. Correlation between the day of mean minimum body temperature and the day of pregnancy termination was low (0.07; > 0.05). Progesterone did not show significant change throughout the study. Body temperature does not seem to be a suitable variable to clinically monitor the aborting effect of aglepristone. Decrease of body temperature after aglepristone treatment could represent further evidence of its hypothalamic effects.     

Repeated induction of abortion in bitches and the effect on plasma concentrations of relaxin, progesterone and estradiol-17beta

The aim of the present study was to investigate the effects of two medications on two subsequent abortions and plasma hormone concentrations of dogs. For this purpose, two groups of bitches (n=5 each), received the antiprogesterone aglepristone (Alizine) at 10mg/kg body weight on two subsequent days around day 30 after mating. In group II, the antiprolactin cabergoline (Galastop) was additionally administered po at 5 microg/kg body weight until the start of abortion. The plasma concentrations of relaxin, progesterone (P4) and estradiol-17beta (E2) were measured before, during and after each abortion. During the next cycle after the abortion, the same bitches were mated again and in pregnant animals, induction of abortion was performed as before. During the third cycle, pregnant bitches were allowed to whelp. Termination of first pregnancy occurred significantly earlier after the combined treatment (6.8 versus 10.6 days, p<0.05). In both groups and during both abortions, relaxin varied between individuals; however, there was a continuous decrease after the abortions and no significant differences between groups (p>0.05). In one bitch with high relaxin concentrations before treatment (11.6 ng/ml), a cystic endometrial hyperplasia was diagnosed. In the aglepristone only group, P4 concentrations increased significantly after the first application (p<0.05), then decreased continuously until day 45 after the beginning of abortion. In the combined group, there was a continuous decrease until day 45 (p>0.05). At this time, P4 concentrations between 0.47 and 84.9 nmol/l were measured in both groups. The level of E2 over time was not influenced by any medication. We therefore note that the two medications mainly influenced plasma concentrations of P4 in different ways, probably due to specific treatment-hormone interactions. However, all measurements fell within the range considered normal.