Intravaginal prostaglandin F2 alpha for the treatment of metritis and pyometra in the bitch

The purpose of this study was to determine whether intravaginal prostaglandin F2 alpha (PGF2 alpha) would be effective for the treatment of metritis or pyometra in the bitch. Seventeen bitches with metritis or pyometra were treated with PGF2 alpha. Prostaglandin F2 alpha (150 micrograms/kg body weight) was administered once or twice daily by infusing 0.3 ml per 10 kg body wt into the vaginal lumen. Bitches were also treated with amoxicillin (15 mg/kg body wt/48 h) and/or gentamicin (4 mg/kg body wt/day) administered as intramuscular (i.m.) injections. Fifteen bitches were treated successfully with intravaginally administered PGF2 alpha for 3 to 12 days and with intramuscularly administered antibiotics for 4 to 12 days. Success of treatment was judged by cessation of vaginal discharge, the absence of fluid in the uterus as determined by ultrasonography, and the overall health status of the animal. As two bitches with pyometra showed clinical deterioration in spite of medical treatment, ovariohysterectomy was performed after the first and the second treatment, respectively. No side effects (salivation, vomiting, diarrhoea, hyperpnoea, ataxia, urination, anxiety, pupillary dilatation followed by contraction) were observed after PGF2 alpha treatment. The disease did not recur during the subsequent oestrous cycles within 12 months after the initial treatment. The results demonstrate that intravaginal administration of PGF2 alpha was effective in 13 dogs (86.6%) with metritis or pyometra, and caused no side effects. Although the study was based on a relatively small number of cases, it is concluded that prostaglandin F2 alpha can be a useful means of treating bitches with metritis or pyometra. However, in severe cases of pyometra ovariohysterectomy is needed.     

Treatment of pyometra in cats, using prostaglandin F2 alpha: 21 cases (1982-1990).

Treatment with prostaglandin F2 alpha (PGF2 alpha) was evaluated in 21 queens with open-cervix pyometra. The PGF2 alpha was administered (0.1 or 0.25 mg/kg of body weight, sc, q 12 to 24 h) for 3 or 5 days. Transient postinjection reactions caused by PGF2 alpha administration included vocalization, panting, restlessness, grooming, tenesmus, salivation, diarrhea, kneading, mydriasis, emesis, urination, and lordosis. Reactions began as quickly as 30 seconds after PGF2 alpha administration and lasted as long as 60 minutes. All queens improved clinically after PGF2 alpha treatment. One month after completion of the initial series, 1 queen required a second series of PGF2 alpha injections before pyometra resolved. Of 21 queens, 20 (95%) resumed normal estrous cycles without further treatment and 17 (81%) delivered normal litter(s). Use of PGF2 alpha is an acceptable treatment for open-cervix pyometra in queens.     

Use of a low dose prostaglandin F2 alpha in bitches

The dosage of Prostaglandin F2 alpha used until the present (100, 250 and 1000 micrograms/kg bw), in order to treat pyometra in the bitch, was accompanied with side effects such as salivation, vomiting and diarrhea. In the present work, the efficiency of low dose Prostaglandin (20 micrograms/kg bw) was examined in two different groups of patients: Group 1: Included 9 bitches pregnant for a period of 5-7 weeks duration. Initially the bitches were treated 3 or 4 times per day with Prostaglandin F2 alpha. In these cases abortion took place within 4 to 11 days. Group 2: 12 dogs, suffering from pyometra, were treated 3 times per day with PGF2 alpha for 8 days. In 9 dogs the pyometra resolved and the bitches came in estrus 2-5 months after treatment. 7 bitches have been mated and 6 of these gave birth to healthy litters. During a follow-up period of at least 10 months there has not been a reoccurrence of pyometra. In 3 out of the 12 dogs the uteri were still enlarged after 8 days of treatment. These bitches underwent ovariohysterectomy and a cystic hyperplasia of the endometrium was diagnosed histologically. The low dose (20 micrograms/kg BW) Prostaglandin F2 alpha induced in all dogs the expulsion of the uterine contents. Side effects during the treatment were not observed.     

Prostaglandin F2 alpha treatment of canine pyometra

Immediate and long-term outcomes of prostaglandin F2 alpha treatment for canine pyometra were studied in 10 bitches. Examination of pretreatment uterine biopsy specimens, taken for histopathologic diagnosis and classification of disease severity, revealed either type III or IV pyometra. Dinoprost tromethamine (0.25 or 0.5 mg/kg of body weight, SC) was given once daily for 3 days. Bitches were bred at the first posttreatment estrus and monitored for a minimum of one year. When pure cultures of Escherichia coli (n = 3) or Staphylococcus aureus (n = 1) were obtained from the vagina, these bacteria also were found in the uterus. Pretreatment WBC counts often did not reflect the severity of histopathologic findings in the uterus, but posttreatment WBC counts were useful in monitoring response to treatment. Four bitches produced a litter within one year of treatment. Four bitches (40%) had recurrence of pyometra within one year of treatment, and these same bitches had another recurrence after an additional prostaglandin treatment. Three additional bitches had a recurrence by 27 months after therapy, establishing a total recurrence rate of 77% (7/9). Results suggested that subclinical disease may persist after treatment, with clinical recurrence during diestrus. Despite the high recurrence rate, it was concluded that this treatment is a practical treatment for canine pyometra when reproduction is desired.     

Use of low dose prostaglandin for the treatment of canine pyometra

Ten bitches with pyometra were treated with prostaglandin F_2α at a dose of 20 μg/kg bodyweight three times daily on consecutive days. Diagnosis was based on clinical signs and radiographic findings. Venous blood samples were collected for haematology and measurement of plasma progesterone levels. The response to treatment was monitored by repeated ultrasonic examinations. The treatment was continued for up to eight days. Seven out of 10 bitches responded well to treatment. The remaining three bitches underwent ovariohysterectomy and a cystic hyperplasia of the endometrium was diagnosed histologically. The results indicated that prostaglandin F_2α used at the low dose is sufficient for medical treatment of certain cases of pyometra. The treatment seems to be most effective in bitches without obvious hormonal imbalance. The aetiology of pyometra is discussed.     

Surgical uterine drainage and lavage as treatment for canine pyometra

Pyometra is a common post-oestral syndrome in bitches. Classical treatment consists of either ovariohystorectomy or medical intervention. Surgical uterine drainage and lavage via direct trans-cervical catheterisation using a 5% povidone-iodine in saline solution was performed successfully in 8 bitches with pyometra. All bitches conceived and whelped without complications subsequent to this treatment. It is concluded that this method offers an effective alternative treatment for canine pyometra with shorter recovery times as well as good clinical recovery and pregnancy rates in bitches destined for further breeding.     

Prevention of pregnancy in the dog with a combination of prostaglandin F2 alpha and bromocriptine

Fifteen mated bitches were given prostaglandin F2 alpha (PGF2 alpha) [250 micrograms/kg body weight] and bromocriptine (10 micrograms/kg BW) twice daily from days 6 to 10 of diestrus. Progesterone concentrations declined during treatment. None of the bitches whelped. Daily treatment with PGF2 alpha and bromocriptine for 5 d appears to induce luteolysis and prevent early pregnancy.     

Treatment of spontaneous pyometra in 22 bitches with a combination of cabergoline and cloprostenol

Twenty-two bitches with ultrasonographically diagnosed spontaneous pyometra were treated with a combination of 5 microg/kg cabergoline per day and 5 mug/kg cloprostenol every third day, and potentiated sulphonamide twice a day. Bitches with either open-cervix or closed-cervix pyometra showed a rapid clinical improvement, associated with a reduction in plasma progesterone concentration, increased vulval discharge and a reduction in the diameter of the uterus. The haematological profiles of 21 of the bitches returned to normal within six days of treatment, and their biochemical profiles returned to normal within nine days; 19 of the bitches were managed successfully by a 10-day period of treatment. Two bitches required a further three days of treatment, and in one bitch with a partial uterine torsion the treatment was not successful. Adverse effects of the treatment were limited to the 60 minutes immediately after the administration of prostaglandin, and included retching, vomiting, mild abdominal straining, diarrhoea and panting. The incidence of adverse effects was reduced after each successive dose of prostaglandin. Eleven of the 21 successfully treated bitches were mated at the next oestrus, and seven became pregnant; their litters were smaller than the published breed averages. In four of the bitches the pyometra recurred after the next oestrus.     

Uterine drainage in the bitch for treatment of pyometra refractory to prostaglandin F2α

Uterine drainage was performed in three bitches with pyometra which had been treated unsuccessfully with PGF_2α. All of the bitches became clinically normal and one of them was mated and gave birth to live puppies. The mode of action of uterine drainage is discussed. Possible advantages of a combination of drainage and prostaglandin treatment are also considered.     

Uterine motility during the estrous cycle: studies in healthy bitches

Natural and drug-induced uterine motilities (UM) were recorded via uterine-implanted catheter-tip pressure transducers in 5 bitches during proestrus and estrus and in 6 bitches during early (30 days) and late (60 days) diestrus. The UM was monitored in unanesthetized bitches for 2 days after the estrous-cycle stage had been determined by vaginal cytologic findings. Natural UM, expressed as Alexandria units (pressure X frequency X duration of contractions), was greatest during estrus, moderate during proestrus, and appreciably decreased or lacking during early and late diestrus. During proestrus and estrus, prostaglandin F2 alpha (5 micrograms/kg of body weight, IV) induced intrauterine pressures of 107 and 115 mm of Hg, respectively, and oxytocin (0.05 USP units/kg, IV) induced pressures of 106 and 116 mm of Hg, respectively. In contrast, the intrauterine pressure values induced by prostaglandin F2 alpha given IV during early and late diestrus were 61 and 58 mm of Hg, respectively, and for oxytocin, were 61 and 51 mm of Hg, respectively. Prostaglandin F2 alpha given IM (50 micrograms/kg) also induced a greater intrauterine pressure during proestrus and estrus than during diestrus. We concluded that in the bitch, natural and drug-induced UM are decreased during early and late diestrus.     

Measurement of C‐reactive protein and Prostaglandin F2α Metabolite Concentrations in Differentiation of Canine Pyometra and Cystic Endometrial Hyperplasia/Mucometra

Canine pyometra is a dioestrus period disease in which systemic inflammatory response syndrome (SIRS) is a common outcome due to the response of the body to the bacterial infection. The purpose of this study was i) to differentiate canine pyometra and cystic endometrial hyperplasia (CEH)/mucometra by measuring serum C‐reactive protein (CRP) and prostaglandin F_2α metabolite (PGFM) concentrations in blood and ii) to compare serum concentrations of CRP and PGFM in bitches with a pathological uterus (pyometra or CEH/mucometra) to concentrations in bitches with a healthy uterus. Mean CRP concentrations were found significantly higher (p < 0.001) in dogs with pyometra compared to those with CEH/mucometra or healthy uterus. However, no statistical difference could be detected between the groups for mean PGFM concentrations. Mean white blood cell count (WBC), alkaline phosphatase (ALP) and total protein concentrations were found significantly higher (p < 0.001) in dogs with pyometra. Escherichia coli was the most frequently isolated microorganism from dogs with pyometra (64.3%). Edwardsiella spp. was detected in a single case of pyometra for the first time. In conclusion, our results demonstrate that serum CRP concentrations were increased in dogs with pyometra and thus we conclude that serum CRP concentration but not PGFM might be useful as a marker to differentiate a case of CEH/mucometra from pyometra in female dogs. To the authors' knowledge, this is the first report in which Edwardsiella spp. has been isolated in the canine uterus.     

Recording uterine motility in the nonanesthetized bitch

Spontaneous and drug-induced uterine motility (UM) was recorded in 5 nonanesthetized bitches for 2 to 4 days. Catheter-tip pressure transducers were surgically implanted in 1 uterine horn, tunneled subcutaneously to exit from the skin over the dorsal lumbar area, and protected by a bandage. On the day after implantation, spontaneous UM was recorded in the awake bitch. Effects of IV prostaglandin (PG) F2 alpha (5 micrograms/kg of body weight) and oxytocin (0.05 USP U/kg) and IM PGF2 alpha (25 micrograms/kg) were measured. Estradiol (1 to 25 micrograms/kg) was administered and the study was repeated 24 hours later. In awake bitches, spontaneous UM was 190% greater than UM in anesthetized bitches. Uterine motility was increased by more than 100% after IV PGF2 alpha or oxytocin and by 52% after IM PGF2 alpha. Estradiol abolished spontaneous UM, but did not affect drug-induced responses. Seemingly, spontaneous and drug-induced UM can be documented in the nonanesthetized bitch.     

子宫蓄脓犬与健康犬子宫内膜基质细胞的分离比较

通过分离子宫蓄脓犬与健康犬子宫内膜基质细胞,观察其生长特性并对其进行细胞免疫荧光鉴定,分析比较该细胞在病犬中是否异常。结果显示,轻度子宫蓄脓犬和健康犬的子宫内膜基质细胞形态和特性基本一致,前者的细胞活性更强,增殖速度较快,可在接种后4 d融合成片,细胞多数呈梭形,少数呈多角状。经细胞免疫荧光鉴定,该细胞表达波形蛋白,阳性率98%以上。结果表明本试验所分离的细胞为犬子宫内膜基质细胞,该细胞在轻度子宫蓄脓犬和健康犬中无明显变化。     

Quantity of IL‐2, IL‐4, IL‐10, INF‐γ, TNF‐α and KC‐Like Cytokines in Serum of Bitches With Pyometra in Different Stages of Oestrous Cycle and Pregnancy

The occurrence of the pyometra is most common in the first half of the dioestrus when there is decreased cellular immunity associated with increased serum concentration of progesterone in females. The aim of this study was to determine the immunological profile of bitches with pyometra, studying serum levels of IL‐2, IL‐4, IL‐10, IFN‐γ, KC‐like and TNF‐α and comparing them with those of healthy bitches in anoestrus, dioestrus and pregnant. Forty females were divided into four experimental groups: group 1 (G1): with pyometra (n = 10); group 2 (G2): bitches in the second week of gestation (n = 10); group 3 (G3): in anoestrus (n = 10); and group 4 (G4): in dioestrus (n = 10). The serum levels for IL‐2, KC‐like, INF‐γ and TNF‐α were similar for all experimental groups. The values obtained for IL‐10 were found increased (p < 0.001) in animals in dioestrus and pyometra compared with females in anoestrus and pregnant, and the levels of IL‐4 observed were significantly greater (p < 0.001) in bitches with pyometra when compared with others. The cytokine profile in animals with pyometra is similar to bitches in dioestrus for IL‐10 and had increase in IL‐4 for bitches with pyometra, which represents an anti‐inflammatory these cases. This suggests the presence of an immunosuppressive state in both cases, which may explain the propensity of bitches in dioestrus to be affected by pyometra and the severity of the disease on these animals.     

Lactoferrin in Canine Sera: A Pyometra Study

The concentration of lactoferrin was measured in canine sera from groups of healthy male dogs as well as pregnant and non-pregnant female dogs and was compared with that of bitches with pyometra. Lactoferrin concentrations were higher in bitches with pyometra. The role of elevated lactoferrin concentrations in the suppression of lymphocyte activity was examined in sera from bitches with pyometra in a series of investigations. Although the sera from bitches with pyometra were capable of suppressing lymphocyte activity, lactoferrin was not found to be involved in this action.     

Follow-up examinations of bitches after conservative treatment of pyometra with the antigestagen aglepristone

The aim of this study was to determine the therapeutic success of the medical treatment of canine pyometra with the antigestagen aglepristone and to document the recurrence rate in relation to the time interval after treatment with antigestagens. In 48 (92.8%) of the 52 treated bitches, healing could be achieved within the first 3 weeks after the treatment had been started. One bitch died as a result of renal insufficiency; in three bitches there was no emptying of the uterus, so ovariohysterectomy became necessary. In these three patients, ovarian and endometrial cysts were present. Forty-one bitches could be followed up for 3 months. Four animals developed a recurrence (9.8%). In three bitches ovarian cysts and cystic endometrial hyperlasia could be found intra operationem. The development of 37 bitches could be followed for at least 1 year. Seven animals developed a pyometra again (18.9%). Two received a repeated treatment with aglepristone and have been free from recurrence for over 12 months. In 37 animals data on the subsequent sex cycles are available. In 22 bitches next heat started at the expected time, in seven animals heat started too early. In eight bitches the period of anoestrus was prolonged. Five of the six bred bitches delivered at least one litter. The presented data show that treatment of pyometra by aglepristone results in a high healing rate. The recurrence rate can be minimized by the selection of bitches without ovarian cysts and cystic endometrial hyperplasia.     

Age‐Related Pregnancy Results and Further Examination of Bitches after Aglepristone Treatment of Pyometra

The cystic endometrial hyperplasia and pyometra complex is one of the most common uterine diseases in bitches. The appearance of pharmacological preparations containing anti‐progestagens created new possibilities for pyometra treatment. The aim of this study was to evaluate the curative effect of the anti‐progestagen aglepristone treatment of pyometra in bitches of different ages. Twenty four bitches of different breeds, aged from 0.8 to 9.5 years (21–48 kg) exhibiting clinical pyometra symptoms (two groups – I ≤ 5 years, n = 14 and II >5 years, n = 10) were evaluated. Information about the general reproductive health was collected up to 54 months after anti‐progestagen treatment. Remission of clinical symptoms and return of blood chemistry results and total leucocyte count to referential values were achieved in all cases within 14 days of treatment. Bitches were naturally mated at the first, and when unsuccessful, the second oestrus after treatment. In group I, no recurrence of pyometra symptoms was observed during following cycle(s). Eight bitches (57.1%) had a full‐term pregnancy and the number of newborn pups ranged from 1 to 12. None of the bitches from the group II became pregnant. In conclusion, the basic indication for conservative pharmacological treatment of pyometra is preserving female fertility and obtaining offspring. The important conditions for successful aglepristone treatment are: the young age (up to 5 years) and the lack of detectible ovarian cysts. It seems necessary to mate bitches in the first or second oestrus after finishing treatment. The efficacy of treatment can be measured by the after‐treatment pregnancy rate.     

Fenprostalene-induced abortion in bitches

A long-acting prostaglandin F(2alpha) analogue, fenprostalene, was subcutaneously administered singly at doses of 5, 10, 25, 50, 100 or 150 microg on day 25 after ovulation during pregnancy in bitches (n=4 for each dosage), and maintenance of pregnancy, changes in plasma progesterone concentration, interval between the treatment and subsequent estrus and conception rate at that estrus were studied. Abortion was associated with a decrease in the plasma progesterone concentration below about 2 ng/ml, and the abortifacient effect was dose-dependent. Administration of 50 microg or more of fenprostalene induced abortion in all dogs 3 to 13 days after the treatment. The interval between administration and subsequent estrus was markedly shorter in the aborted bitches than in the non-aborted ones (P<0.01). The conception rate at the estrus in the aborted dogs was 50%, whereas all of the bitches who had not aborted became pregnant. The results indicate that a single administration of fenprostalene could induce abortion during mid-pregnancy in bitches, and the subsequent estrus may come early with a low conception rate.     

Urinary gamma-glutamyl transferase and the degree of renal dysfunction in 75 bitches with pyometra

In 75 bitches with pyometra single urine samples were examined for gamma-glutamyl transferase (gamma-GT), protein, glucose, specific gravity, bacteria, red blood cells and white blood cells. Serum samples were examined for urea, creatinine, inorganic phosphate and gamma-GT. Biochemical findings were compared with the degree of illness (clinical signs). Twenty one bitches had no signs of renal disease. Seventeen showed only glomerular damage indicated by proteinuria without signs of proximal tubular damage. Thirty seven bitches had increased urinary gamma-GT levels, indicating proximal tubular lesions, which were associated with proteinuria in 35 and renal failure in 16 of them, and worse clinical findings. In all bitches with pyometra serum levels of gamma-GT were comparable to values in control bitches. Glomerular dysfunction seemed to precede proximal tubular lesions, so that gamma-GT-uria in bitches with pyometra was not an early but rather a late indication of a more profound degree of renal dysfunction, that is, proximal tubular renal damage developed after glomerular dysfunction and preceding renal failure.     

Laparoscopic sterilization of the bitch and queen by uterine horn occlusion

Laparoscopic sterilization techniques, originally developed for use in women, were evaluated in the bitch and queen. In the first study (study I), the uterine horns of 6 bitches and 3 queens were occluded by electrocoagulation or plastic clips. The sites of occlusion were midway along the length of 1 cornus and at the uterotubal junction on the contralateral side. Both procedures effectively occluded the uterine horns, as evidenced by a distinctly visible separation of the reproductive tract. Laparoscopic examination 1 year after surgery revealed an enlarged, thin-walled, and fluid-filled uterine segment cranial to the midcornus occlusion sites in all animals. The contralateral horn was normal in appearance, except for the separation from the ovarian bursa. Three of the bitches developed pyometra (confined to the distended uterine segment) at 24 months, at 53 months, and at 72 months after sterilization, respectively. In a subsequent study (study II), 1 adult and 5 prepubertal bitches were sterilized by laparoscopic electrocoagulation of both uterine horns at the uterotubal junction adjacent to the ovarian bursa. Upon reexamination 1, 2, and 4 years later, the uterine horns of these females were normal in appearance, but were separated from the adjacent ovarian bursae. These females continued to be clinically healthy. Laparoscopic sterilization offers a rapid and safe alternative to ovariohysterectomy and, because of its minor invasive nature, can be performed on young, prepubertal animals. Such a procedure may have particular value as a simple, practical means of sterilizing dogs and cats on a mass basis.