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Aglepristone efficiency with and without the canine pyometra cloprostenol/Eficacia del aglepristone con y sin cloprostenol en el tratamiento del piometra canino.

INTROODUCTION

Pyometra is a uterine pathology of bacterial origin stimulated by progesterone during consecutive heat cycles, and by an exogenous estrogen and/ or progesterone treatment (1). It is reported principally in females over six years of age (2,3).

It is a pathological process that usually begins with cystic endometrial hyperplasia (CEH), and that permits the proliferation of vaginal bacteria, accumulating purulent material inside the uterus (3-5). It is considered one of the most frequent pathological alterations in canine reproduction (4, 6). It begins during the estrous phase of the reproductive cycle, by morphological changes induced by progesterone (P4) and estrogen (E2), along with an abnormal response in the uterus during the luteal phase, which combined with bacterial action results in pyometra (5,7). Two clinical forms are distinguished: closed pyometra, whose signs are very severe and open pyometra. Some of the common signs are: vomiting, polydipsia, polyuria and anorexia (2,3,5).

Treatment of pyometra should be urgent and aggressive, including the extraction of contents, which is generally surgical in 80% of cases (8- 10). None the less, pharmacological treatment is also possible (11-13). The effectiveness of the use of natural prostaglandin F2[alpha] has been traced in 55% of cases of open pyometra and 24% of closed pyometra, respectively (14-16). It was found least effective in cases of closed pyometra (24%), which brought about the use of progesterone antagonists like aglepristone (15,17), which improve efficacy when combined with prostaglandins, above all, in order to carry out therapies in bitches of high economic value and where surgery is not an option (18).

The principal cause of canine pyometra, in 90% of cases, is Escherichia coli in 90% of cases (2,6,19), which penetrates the uterus during estrus (5,19,20). For this reason treatment should always be accompanied by antibiotics or antimicrobials, especially with a spectrum against Gram-negative microorganisms such as gentamicin, amikacin, enrofloxacin, ciprofloxacin, among others (19).

Females treated jointly with progesterone antagonists and natural or synthetic prostaglandins F2[alpha] were 75% of the time cured (11,15,17), while patients that only received prostaglandins only reached 60% (13). This is due to the fact that the canines presented less uterine response to the use of prostaglandins (11, 160); other treatments have been mentioned as having similar results (8,12,18). Among these Corrada et al (14) describe the effectiveness of using dopamine agonists (Cabergoline) in treating canine pyometra.

Various studies demonstrated the cure of pyometra with only a single use of 10 mg/kg of antiprogestin aglepristone subcutaneously on days 1, 2 and 8 of the diestrus, combined with cloprostenol, which induces the opening of the cervix and the resulting drainage of the uterus (13-15). Other protocols with an efficacy of 95% are: 10 mg/kg of aglepristone subcutaneously on days 1, 3, 8, and 15 of the diagnosis, combined with cloprostenol 1 [micro]g/kg subcutaneously on days 3 and 8, or both combined on days 3, 5, 8, 10, 12 and 15 (13,18). Only Molina (18) describes using aglepristone as a singular therapy in a report on the case of a French Bull Dog with pyometra. However, the efficacy of aglepristone as a singular medicine for this treatment has not been determined in a comparative study.

The objective of the present study was to value the efficacy of the antiprogestin aglepristone with and without cloprostenol in treating pyometra in female canines.

MATERIAL AND METHODS

Study location. Veterinary Clinic of Antioquia, Medellin Colombia, from 2011 to 2013.

Animals. 10 female French Bulldogs, between 3-8 years of age, diagnosed with closed pyometra.

All animals used were of high breeding value because of which their owners sought alternative therapy to conventional ovariohysterectomy. All bitches had closed pyometra, with clinical signs of polydipsia, polyuria, vomiting, lack of energy and anorexia; as well as their last heat being 45-60 days prior.

Experimental design and treatments. The females were randomly assigned to one of the two treatment groups, one with a 10 mg/kg dose of aglepristone administered subcutaneously on days 1, 2, 8, 14 and 28; the other with a 10 mg/kg dose of aglepristone administered subcutaneously on days 1, 3, 8 and 15, and 1 [micro]g/kg of cloprostenol given subcutaneously on days 3 and 8. Both groups received a complementary therapy with 5 mg/kg of enrofloxacin given orally every 12 hours for 28 days.

The pyometra diagnosis in all patients was made by means of a clinical exam, blood profile, as cited later on, and confirmation by echography.

Evaluation of the bitches. The hematological evaluation was carried out starting with blood samples from the jugular vein, gathered in tubes with EDTA on days 1 and 28 of the diagnostic. The samples were processed on Abacus junior vet[R] (Diatron Ltda, Austria) equipment according to the following parameters: hematocrit (HCT), hemoglobin (HGB), mean corpuscular hemoglobin concentration (MCHC), erythrocytes, leukocytes, neutrophils (N), eosinophils (E), lymphocytes (L), lemniscus (B), monocytes (M), platelets (PL) and plasma proteins.

The evaluation of uterine contents was made with an abdominal echography using a Midray DP 3300 B/N[R] system every 8 days, during the 28 days of treatment. In addition, the follow- up included: time until the next proestrus (by vaginal smear and progesterone measurements above 8 mg/ml), the days of expulsion uterine content and the time of clinical recuperation of each patient, measured by the absence of clinical signs; among which were evaluated: absence of vomiting, absences of abdominal pain through palpation, measured according to the Universidad de Melbourne (UMPS) pain scale, return of appetite and normal activity. The evaluation of the patient was ambulatory until resolving the symptoms.

The females were paired and naturally mated on days 11, 14 and 16 from the initial day of proestrus. For this study only the presence or absence of gestation was evaluated by echography 23 days after copulation; no further monitoring was carried out on the non-pregnant females.

Statistical analysis. The variables were subject to ANOVA, with Tukey HSD and [Chi.sup.2] tests for qualitative variables and with a non-parametric test (Mann Whitney test).

Informed consent. All owners of the bitches signed a consent form, accepting the administration of medication as an alternative to ovariohysterectomy. The investigation was approved by the University Corporation of Sabanet (Unisabaneta) ethics committee, by means of resolution 001 on October 2013.

RESULTS

Ten female French Bulldogs were evaluated, of which there was not found a significant difference between groups and protocols (p>0.05). In the aglepristone group the average age was 4.2 [+ or -] 1.92 years and in the combined aglepristone and cloprostenol group 3.2 [+ or -] 1.30 years.

In the hemogram evaluation during the two periods, day 0 and 28, no variation in the red line was observed, neither before nor after the treatment (Table 1), there was no significant difference between inter or intra treatments (p [greater than or equal to] 0.05).

In the leukogram there was no statistical difference found between aglepristone and aglepristone in addition to cloprostenol (p [greater than or equal to] 0.05), but there a difference was found between the values on day 0 and 28. For this reason the information from both treatment groups was analyzed together for each variable and time measurement. In this analysis it was found that all variables analyzed by the leukogram showed lesser post treatment values (Table 2). These results show that both treatments decreased the number of white blood cells, neutrophils and lemniscus', compared with the values before treatment (p [less than or equal to] 0.05).

There was no significant difference (p [greater than or equal to] 0.05) between both protocols in regards to days of recuperation for the following clinical variables: days until the next proestrus (138 days), days until a normal echography (15 days), days until absence of vomiting (6.2 days) and days until an absence of polydipsia/polyuria (5.6 days) (Table 3). However, variables such as the days of absence of abdominal pain, days of vaginal secretion, days until normal appetite and days of normal activity, showed statistical differences (p [greater than or equal to] 0.05), being less for the combined aglepristone and cloprostenol group (Table 3).

All 5 females in each protocol paired during their first heat. Of them, 40% (3 out of 5) of the aglepristone group became pregnant, with a diagnostic echography on day 23 post mating, while only 20% (1 out of 5) of the aglepristone and cloprostenol group were impregnated. All pregnant females carried their pregnancy to full term. The present study did not evaluate the number of puppies or the vitality and malformation of the neonates. None of the bitches showed adverse clinical signs or local effects associated with the treatments.

DISCUSSION

The presence of the disease does not coincide with population data found by other authors, and there is no particular prevalence according to breed, thus, the French Bulldog was chosen in particular because of its high economic value. The table refers to females greater than four years of age, as mentioned by other authors (2,3), which does not coincide with the present work where the age was 4.2 years for the aglepristone group and 3.2 years for the aglepristone and cloprostenol group, indicating that they were young females, one cannot infer that the French Bulldog as a breed is the explanation, since pyometra has been found in young animals of different breeds (3).

The results indicate that treatments with aglepristone or aglepristone with cloprostenol probably have similar results as regards to the values of the full blood count. It is evident that the increase in the number of white blood cells, neutrophils and lemniscus' are characteristic to canine pyometra, as mentioned by many authors (15, 21). However, the aglepristone and the aglepristone with cloprostenol treatments, combined with antimicrobials, allowed the recuperation of the altered leukogram variables, which agrees with the results of other studies (19,21), where the use of both protocols mitigates leukocytosis and neutrophil by eliminating pyogenic material. Moreover, the use of enroflaxacin proved to be effective in the control of the infection, similar to those already mentioned for gentamicin in another study (19).

All bitches in this study presented uterine contents in the ultrasound evaluation, from 15 days on average which coincide with the results of other authors (13,15,18). Also, both treatments showed a similar behavior in regards to days of recuperation of the clinical variables: days of proestrus, days until absence of vomiting and days until absence of polydipsia/polyuria (15, 16). Treatment with a combination of aglepristone and cloprostenol showed an advantage in regards to days of secretion, with an average of 7.2 days compared with 10 days for treatment with only aglepristone. This coincides with other studies where the greater effect of this combination is confirmed (22); none the less, this data differ from the 3 days of secretion reported by those who used at least one protocol of aglepristone with cloprostenol similar to that of this study (17). In vitro studies have demonstrated that the progesterone antagonist induced by aglepristone improves contractile activity of the myometrium induced by prostaglandins (16), which clinically implies assistance in the elimination of pyogenic material in less time, facilitating recuperation.

In this study the lowest average number of days until absence of pain, and days to normal activity and appetite associated with the combined treatment of aglepristone with cloprostenol, is related to the lowest number of days of uterine discharge and improvement of clinical evaluation, which can be related to studies that indicate a higher contractile capacity of the myometrium from the combination of aglepristone with cloprostenol than only aglepristone (15,18). However, the present study did not determine values according to the UMPS scale, it was only used to determine presence or absence of pain and this was observed when values decreased, indicating improvement.

None of the bitches in this study had a recurrence of the disease, at least not in the estrous cycle subsequent to this study, which does not rule out the occurrence of the disease in the rest of the subsequent estrous cycles, because they could not be evaluated in this study. The group of bitches in this study were young, none of which passed 7 years of age, which coincides with previous studies where there was no recurrence of the disease in the following cycle in animals less than 5 years of age and from which it is concluded that better results in preserving female fertility is obtained in young animals (23).

In the present study no side effects associated with the use of prostaglandins was found, such as: vomiting, sialorrhea, nausea, diarrhea, hypotension, tachycardia, shock and death, as is described in handling doses of 2.5 [micro]g/kg (16). Similar circumstances were reported by other canine studies (13). This could be due to the use of low doses of cloprostenol in this study. Further, neither the aglepristone treatment reported side effects, which compares with the results of previous studies (24).

These results should continue to be analyzed, even though there is clinical evidence that the combination of aglepristone with cloprostenol can generate better results, as are describes by Gobello et al (13), Fieni (15) and Jena et al (21), in curing patients. The present study demonstrates that only using aglepristone is sufficient for guaranteeing the recuperation of the patient, similar to what is described by Molina (18). The analysis should be guided toward not only guaranteeing future fertility, but also to avoid side effects and risk to the life of the female, through the use of synthetic prostaglandin (16,25).

In addition, to dispute the concept that pyometra is a reproductive disease in female canines that requires surgical treatment (3,5,26), due to the pathogenicity of its etiologic agent and its death rate (2,3,21), it is known that procedures like the ovariohysterectomy, which eliminates possible recurrence (11), leave breeding females without the possibility of progeny. None the less, surgical treatments have their limits when the surgical risk increases or the owner refuses OVH because they are patients of high breeding value, in which the possibility of sterilization is considered expensive (20).

It is at this point where progesterone antagonists play an important role, especially the use of aglepristone, which due to its medical advantage in facilitating the contractibility of the myometrium, permits the elimination of pyogenic material (12,15,26), relaxing the uterine neck, due to its competitive effect against progesterone (17). Compared to the use of prostaglandin, which smooth the corpus luteum (16), giving the doctor a new possibility of high effectiveness in treating both open and closed pyometra. Reports are found where the use of aglepristone as the sole medication achieved beneficial curative effects greater than 75% (11); similar to those mentioned by Molina (18), where the patient was completely cured, while the complementary use of aglepristone with prostaglandin F2[alpha] was 90% effective (7,15). Achieving recuperation within the first 3 weeks after initiating the treatment; with a short-term successful healing rate of 92.3%, the use of aglepristone as the only tool is certainly justifiable.

The therapeutic response to the use of aglepristone was excellent with no side effects. In addition, the presence of two treatment protocols allows the veterinarian the opportunity to manage medication depending on the severity of the case.

In conclusion, treatments with aglepristone and a combination of aglepristone with cloprostenol, along with enrofloxacin, permit the recuperation of the animal with pyometra in the variables of the full blood count on day 28; nonetheless, the combination of aglepristone with cloprostenol obtained better results in the recuperation of the treated females.

Acknowledgements

To the Veterinary Clinic of Antioquia for allowing us to use their facilities and patients for the present study. To the Corporacion Universidad de Sabaneta and to Caequinos for providing the technical personnel for the present study.

INTRODUCCION

El piometra es una patologia uterina de origen bacteriano favorecida por accion de la progesterona durante ciclos de celos sucesivos, tambien por una terapia exogena con estrogenos y/o progestagenos (1). Se reporta principalmente en hembras mayores de 6 anos (2,3).

Es un proceso patologico que suele iniciar con hiperplasia endometrial quistica (HEQ), y que permite la proliferacion de bacterias provenientes de la vagina, llevando a la acumulacion de material purulento al interior del utero (3-5). Es considerada como una de las alteraciones patologicas mas frecuentes en reproduccion de caninos (4,6). Se inicia en la fase estral del ciclo reproductivo, por cambios morfologicos inducidos por la progesterona (P4) y los estrogenos (E2), con una respuesta anormal del utero en la fase lutea, que unido a la accion bacteriana ocasiona el piometra (5,7). Se distinguen dos formas clinicas: piometra de cuello cerrado, cuyos signos son mas severos y el piometra de cuello abierto. Algunos de los signos comunes son: vomito, polidipsia, poliuria y anorexia (2,3,5).

El tratamiento del piometra debe ser urgente y agresivo, con la extraccion del contenido, que por lo general es quirurgico en el 80% de los casos (8- 10). Sin embargo, el tratamiento farmacologico tambien es posible (11-13). La efectividad en el uso de prostaglandina natural F2[alpha] se ha descrito en el 55% de casos de piometra abierto y 24% en piometra cerrado, respectivamente (14-16). La menor efectividad encontrada en los casos de piometra cerrado (24%), llevo al uso de antagonistas de

la progesterona como aglepristone (15,17), los cuales mejoraron la efectividad al unirse con las prostaglandinas, sobre todo para realizar terapias en perras de alto valor economico y donde la cirugia no es una opcion (18).

El principal agente causante del piometra canino es Escherichia coli en el 90% de los casos (2,6,19), el cual penetra al utero durante el estro (5,19,20). Por ello el tratamiento debe ir siempre acompanado de antibioticos o antimicrobianos, en especial con espectro contra microorganismos Gram negativos como lo son la gentamicina, amikacina, enrofloxacina, ciprofloxacina, entre otros (19).

Las hembras tratadas conjuntamente con antagonistas de la progesterona y prostaglandinas F2[alpha] natural o sinteticas curan en un 75% (11,15,17), mientras que pacientes que solo reciben prostaglandinas lo hacen hasta en el 60% (13). Lo cual se debe a que los caninos presentan menor respuesta uterina al solo uso de prostaglandina (11,16); otros tratamientos se han descrito con resultados similares (8,12,18). Dentro de los cuales Corrada et al (14), describen la efectividad del uso de agonistas de la dopamina (Cabergolina) en el tratamiento del piometra canino.

Varios estudios demostraron resolucion del piometra con el solo uso del antiprogestageno aglepristone a dosis de 10 mg/kg subcutaneo, los dias 1,2 y 8 del diestro, unido a cloprostenol, el cual induce la apertura del cervix y el consiguiente drenaje uterino (13-15). Otros protocolos con eficacia del 95%, son: aglepristone 10 mg/kg subcutaneo a los dias 1, 3, 8, y 15 del diagnostico, combinado con cloprostenol 1 [micro]g/kg subcutaneo los dias 3 y 8, o bien ambos combinados los dias 3, 5, 8 10, 12 y 15 (13,18). Pero solo Molina (18) describe el uso de aglepristone como unica terapia en un reporte de un caso de una Bulldog frances con piometra. Pero no se ha determinado la efectividad del aglepristone como unico medicamento para este tratamiento, en un estudio comparativo.

El objetivo del presente estudio fue valorar la eficacia del antiprogestageno aglepristone con y sin el cloprostenol en el tratamiento del piometra en hembras caninas.

MATERIALES Y METODOS

Sitio de estudio. Clinica Veterinaria de Antioquia, Medellin Colombia, entre los anos 2011 a 2013.

Animales. 10 hembras caninas de la raza Bulldog Frances, entre 3-8 anos de edad, con diagnostico de piometra cerrado.

Todas las hembras utilizadas eran animales de alto valor reproductor por lo que el propietario buscaba otra alternativa terapeutica diferente a la ovariohisterectomia convencional. Todas las perras presentaron piometra cerrado, con los signos clinicos de polidipsia, poliuria, vomito, decaimiento y anorexia; Asi como historia de celo hace 45-60 dias.

Diseno experimental y tratamientos. Las hembras fueron asignadas de manera aleatoria a uno de los dos grupos de tratamiento, un grupo con aglepristone a dosis de 10 mg/kg subcutaneo los dias 1, 2, 8, 14 y 28; el otro con aglepristone a dosis de 10 mg/kg subcutaneo los dias 1, 3, 8 y 15, mas cloprostenol 1 [micro]g/kg subcutaneo el dia 3 y 8. Ambos grupos recibieron una terapia complementaria con enrofloxacino 5 mg/kg via oral cada 12 horas por 28 dias.

El diagnostico de piometra en todas las pacientes fue realizado mediante el examen clinico, perfil sanguineo como se cita a continuacion y confirmados por ecografia.

Evaluacion de las perras. La evaluacion hematologica fue realizada a partir de muestras de sangre de la vena yugular, recolectada en tubos con EDTA los dias 1 y 28 del diagnostico. Las muestras fueron procesadas en equipo Abacus junior vet[R] (Diatron Ltda, Austria) para los siguientes parametros: hematocrito (Hto), hemoglobina (Hg), volumen corpuscular medio (VCM), hemoglobina corpuscular media (HgCM), concentracion de hemoglobina corpuscular media (CHgCM), eritrocitos, leucocitos, neutrofilos (n), eosinofilos (E), linfocitos (L), bandas (B), monocitos (M), plaquetas (PL) y proteinas plasmaticas.

La evaluacion del contenido uterino, se realizo mediante ecografia abdominal con un equipo Midray DP 3300 B/N[R] cada 8 dias, durante los 28 dias de tratamiento. Ademas, el seguimiento incluyo: tiempo de retorno al proestro (por citologia vaginal y mediciones de progesterona por encima de 8 mg/ml), los dias de expulsion del contenido uterino y el tiempo de recuperacion clinica de cada paciente, medido por la ausencia de signos clinicos; dentro de los cuales fueron evaluados: ausencia de vomito, ausencia de dolor abdominal por palpacion, medido segun escala de dolor Universidad de Melbourne (UMPS), retorno del apetito y retorno de actividad normal. La evaluacion del paciente fue realizada de manera ambulatoria hasta resolver los signos.

Las hembras fueron apareadas con monta natural los dias 11, 14 y 16 de iniciado el proestro. Para este estudio solo fue evaluada la presencia o ausencia de la gestacion por ecografia a los 23 dias de la copula; a las hembras no gestantes no se les realizo seguimiento posterior.

Analisis estadistico. Las variables fueron sometidos a ANOVA, con el test de HSD Tukey y [Chi.sup.2] para las variables cualitativas y con test no parametrico (Mann Whitney test).

Consentimiento informado. Todos los propietarios de las hembras firmaron un consentimiento informado, aceptando la realizacion de la medicacion como alternativa a la ovariohisterectomia. La investigacion fue aprobada por el comite de etica de la Corporacion Universitaria de Sabaneta (Unisabaneta), mediante resolucion numero 001 de octubre 2013.

RESULTADOS

Diez hembras Bulldog Frances fueron evaluadas, de las cuales para el grupo de aglepristone la edad promedio fue 4.2 [+ or -] 1.92 anos y de 3.2 [+ or -] 1.30 anos para el aglepristone mas cloprostenol, no se encontro diferencia significativa entre grupos y protocolos (p [greater than or equal to] 0.05).

En la evaluacion del hemograma durante los dos tiempos dia 0 y 28, no se observo variacion en la linea roja, ni antes ni despues del tratamiento (Tabla 1), no hubo diferencia significativa inter o intra tratamientos (p [greater than or equal to] 0.05).

En el leucograma no se encontro diferencia estadistica entre aglepristone y aglepristone mas cloprostenol (p [greater than or equal to] 0.05), pero si encontro una diferencia entre los valores del dia 0 y 28. Por esto se analizaron en conjunto los datos de los dos grupos de tratamiento por cada variable y momento de medicion. En este analisis se encontro que todas las variables analizadas del leucograma mostraron valores menores postratamiento (Tabla 2). Estos resultados muestran que ambos tratamientos disminuyeron los valores de los globulos blancos, neutrofilos y bandas, comparado con los valores antes del tratamiento (p [less than or equal to] 0.05).

No hubo diferencias significativas (p [greater than or equal to] 0.05) entre ambos protocolos para los dias de recuperacion de las siguientes variables clinicas: dias de retorno al proestro (138 dias), dias para ecografia aparentemente normal (15 dias), dias para ausencia de vomito (6.2 dias) y dias para ausencia de polidipsia/poliuria (5.6 dias) (Tabla 3). Pero las variables dias de ausencia de dolor abdominal, dias de secrecion vaginal, dias a apetito normal y dias de actividad normal, mostraron diferencia estadistica (p<0.05), siendo menor para el grupo de Aglepristone cloprostenol (Tabla 3).

Las 5 hembras de cada protocolo se aparearon en el primer celo. De ellas, el 40% (3 de 5) del grupo de aglepristone quedo gestante, con diagnostico ecografico a los 23 dias pos monta, mientras que solo el 20% (1 de 5) del grupo aglepristone y cloprostenol quedo prenada. Todas las hembras gestantes presentaron una gestacion a termino. En el presente estudio, no se evaluo el numero de cachorros, vitalidad y malformacion de los neonatos. Ninguna de las perras mostro signos clinicos adversos o efectos locales asociados con los tratamientos.

DISCUSION

La presencia de la enfermedad no coincide con los datos poblacionales encontrados por otros autores, pero no hay prevalencia en particular segun la raza, debido a que se escoge una raza en particular Bulldog frances, por tratarse de animales de alto valor economico. La edad descrita por otros autores refiere el cuadro a hembras mayores de 4 anos (2,3), lo cual no coincide en el presente trabajo donde las edades estaban en 4.2 para el aglepristone y 3.2 anos para aglepristone mas cloprostenol respectivamente, lo cual indica que se trataba de hembras jovenes, no se puede inferir que por tratarse de la raza Bulldog frances esta sea la explicacion pues el piometra se ha descrito en animales jovenes de diferentes razas (3).

Los resultados indican que probablemente los tratamientos con aglepristone o aglepristone con cloprostenol, tienen resultados similares en cuanto a los valores del hemoleucograma. Es evidente que los valores aumentados de los globulos blancos, neutrofilos y bandas son caracteristicos del piometra canino, como los describen muchos autores (15,21). Pero el tratamiento con aglepristone y aglepristone con cloprostenol, combinados con antimicrobianos, permitieron la recuperacion de las variables del leucograma alteradas, lo que concuerda con resultados de otros estudios (19,21), donde la leucocitosis y neutrofilia sede al uso de ambos protocolos, debido a la eliminacion del contenido piogeno. Ademas, el uso de enrofloxacina, demostro ser eficaz, en el control de la infeccion, similar a los ya descritos para la gentamicina en otro estudio (19).

Todas las perras de este estudio a la evolucion ecografica presentaron contenido uterino, a partir del dia 15 en promedio y coincide con los resultados de otros autores (13,15,18). Ademas, ambos tratamientos mostraron un comportamiento similar en los dias de recuperacion de las variables clinicas dias de proestro, dias a ausencia de vomito y dias a ausencia de polidipsia/poliuria (15,16). En el tratamiento de aglepristone con cloprostenol se observa una ventaja en los dias de secrecion, con un promedio de 7.2 dias comparado con los 10 dias del tratamiento con aglepristone solo y coincide con otros estudios donde se ratifica el mejor efecto de esta combinacion (22); sin embargo, estos datos difieren de los 3 dias de secrecion reportados por quienes utilizaron al menos un protocolo de aglepristone y cloprostenol similar al de este estudio (17). Estudios in vitro han demostrado que el antagonismo de la progesterona inducido por el aglepristone mejora la actividad contractil del miometrio inducido por las prostaglandinas (16), lo que clinicamente implica que se favorece la eliminacion del contenido piogeno en menor tiempo, favoreciendo la recuperacion.

En este estudio el menor promedio de dias a ausencia de dolor, dias a actividad normal y dias a apetito normal asociadas a la adicion del tratamiento de aglepristone con cloprostenol, esta relacionado con el menor numero de dias de descargas uterinas y la mejora de la evolucion clinica puede estar relacionada con los estudios que indican una mayor capacidad contractil del miometrio de aglepristone con cloprostenol, que aglepristone solo (15,18). Pero el presente estudio no determina los valores segun la escala UMPS, solo se uso para determinar presencia o ausencia de dolor y esto se dio cuando los valores disminuyeron como indicativo de mejoria.

Ninguna de las perras de este estudio presentaron recidiva de la enfermedad al menos en un ciclo estral posterior a este estudio, lo que no descarta la presencia de esta enfermedad en los demas ciclos posteriores, que para este estudio no pudieron ser evaluado. El grupo de perras de este estudio fue joven pues ningun animal supero los 7 anos de edad y coincide con estudios previos en donde no hubo reincidencia de la enfermedad en el siguiente ciclo en animales menores de 5 anos y de donde se concluye que se obtienen mejores resultados en preservar la fertilidad de la hembras tratadas en animales jovenes (23).

En el presente estudio no se encontraron efectos colaterales asociados con el uso de prostaglandinas, como: vomito, sialorrea, nauseas, diarrea, hipotension, taquicardia, choque y muerte, como se describen con el manejo de dosis de 2.5 [micro]g/kg (16). Similares circunstancias fueron de reportadas por otros estudios en caninos (13), esto se puede deber al uso de bajas dosis de cloprostenol utilizadas en este estudio, ademas, el tratamiento con aglepristone tampoco reporto efectos colaterales comparado con los resultados de estudios previos (24).

Estos resultados deben seguir siendo analizados, pues aunque hay evidencia clinica de que la combinacion aglepristone con cloprostenol, puede generar mejores resultados, como los descritos por Gobello et al (13), Fieni (15) y Jena et al (21), en la curacion del paciente. El presente estudio demostro que solo el uso de Aglepristone es suficiente para garantizar la recuperacion del paciente, similar a los descrito por Molina (18). El analisis debe ser encaminado no solo a garantizar la fertilidad futura, sino de evitar los efectos colaterales y el riesgo para la supervivencia de la hembra, tras el uso de la prostaglandina sintetica (16,25).

Ademas, controvertir el concepto de que el piometra como enfermedad reproductiva de la hembra canina, es una enfermedad de tratamiento quirurgico (3,5,26), debido a la patogenicidad de su agente etiologico y su mortalidad (2,3,21), pues se sabe que los procedimientos como la ovario histerectomia, que elimina la posible recurrencia (11). Pero dejan a las hembras reproductoras sin la posibilidad de progenie. Sin embargo, los tratamientos quirurgicos tienen sus limites donde el riesgo de cirugia se incrementa o existe el caso donde el dueno reproche la OVH porque son pacientes de alto costo reproductivo, en el que la posibilidad de esterilizaciones se considera onerosa (20).

Es en este punto donde los antagonistas de la progesterona juegan un papel importante, en especial el uso del aglepristone, que debido a su ventaja farmacologica al facilitar la contractibilidad del miometrio, permite la eliminacion del contendido piogeno (12,15,26), relajando el cuello uterino, debido a su efecto competitivo frente a la progesterona (17). Comparado con el uso de prostaglandina, que lisa el cuerpo luteo (16), este permite al clinico una nueva posibilidad de alta efectividad en el tratamiento del piometra tanto abierto como cerrado, se encontro reportes donde solo el uso del aglepristone como unico medicamento logro efectos beneficos curativos por encima del 75% (11); similar a lo descrito por Molina (18), donde encontro una recuperacion total del paciente. Mientras que el uso complementario de aglepristone con prostaglandina F2[alpha], alcanzo el 90% de efectividad (7,15). Logrando la recuperacion dentro de las 3 primeras semanas despues de iniciado el tratamiento; con una tasa de curacion exitosa de corto plazo de 92.3%, el uso de aglepristone como unica herramienta es ciertamente justificable.

La respuesta terapeutica al uso de aglepristone fue excelente con efectos secundarios nulos, ademas, la presencia de dos protocolos de tratamiento permiten al medico veterinario tratante la oportunidad de manejar la medicacion dependiendo de la severidad del cuadro.

En conclusion los tratamientos con aglepristone y aglepristone con cloprostenol, mas combinacion con enrofloxacina, permitieron la recuperacion de los animales con piometra en las variables de hemoleucograma al dia 28 de evolucion; sin embargo, la combinacion aglepristone con cloprostenol obtuvo mejores resultados en la recuperacion de las hembras tratadas.

Agradecimientos

A la colaboracion de la Clinica Veterinaria de Antioquia, por facilitar las instalaciones y pacientes para la presente investigacion. A la Corporacion Universitaria de Sabaneta y a Caequinos por proveer el personal tecnico para el presente estudio.

REFERENCIAS

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(9.) Fossum TW. Cirugia en pequenos animales. Barcelona: Elsevier; 2009.

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(25.) Poci Palumbo MI, da Conceicao LC, de Araujo Machado LH, Gomes Lourenco ML, Almeida Moreira S, Legatti E, et al. Toxic acute hepatitis associated to the administration of prostaglandin in a dog. Cienc Rural 2011; 41(9):1578-81.

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Victor Molina D, [1] * M.Sc.

[1] CAEQUINOS-Unisabaneta. Grupo de investigacion RICERCA, Calle 75 Sur N 34-120, Sabaneta, Colombia. * Correspondencia: dooncanmc@hotmail.com

Received: August 2014; Accepted: February 2015.
Table 1. Average values ([+ or -] D.S) of some hemogram
variables during the evaluation of the
pyometra treatment.

                               Hematocrit (%)

Treatment                 Day 0             Day 28

Aglepristone Group         43.2              42.6
                     [+ or -] 5.9 (a)   [+ or -] 3.8 (a)

Aglepristone               43.4              42.2
cloprostenol Group   [+ or -] 3.4 (a)   [+ or -] 2.6 (a)

                              Hemoglobin (g/dl)

Treatment                 Day 0              Day 28

Aglepristone Group         14.4               14.2
                     [+ or -] 1.9 (a)   [+ or -] 1.3 (a)
Aglepristone               14.5               14.0
cloprostenol Group   [+ or -] 1.2 (a)   [+ or -] 0.9 (a)

                              Red blood cells
                              (1 x [10.sup.6]/ml)

Treatment                 Day 0              Day 28

Aglepristone Group         4.0                4.4
                     [+ or -] 0.4 (a)   [+ or -] 0.3 (a)
Aglepristone               4.5                4.6
cloprostenol Group   [+ or -] 0.5 (a)   [+ or -] 0.5 (a)

(a) None of the variables had significant difference (p>0.05).

Table 2. Average values ([+ or -] DS) of the leukogram for French
Bulldog bitches with pyometra and treated with aglepristone alone
or combined with cloprostenol.

                               White blood cells
                              (1 x [10.sup.3]/ml)

Treatment                  Day 0              Day 28

Aglepristone Group          20.7               14.6
                      [+ or -] 0.9 (a)   [+ or -] 1.2 (b)

Aglepristone                20.1               13.7
cloprostenol Group    [+ or -] 2.3 (a)   [+ or -] 0.9 (b)

                                 Neutrophils
                              (1 x [10.sup.3]/ml)

Treatment                  Day 0              Day 28

Aglepristone Group          16.1               9.5
                      [+ or -] 0.6 (a)   [+ or -] 0.6 (b)

Aglepristone                14.7               8.8
cloprostenol Group    [+ or -] 1.2 (a)   [+ or -] 0.9 (b)

                                   Lemniscus'
                              (1 x [10.sup.3]/ml)

Treatment                  Day 0              Day 28

Aglepristone Group          0.7                0.2
                      [+ or -] 0.2 (a)   [+ or -] 0.2 (b)

Aglepristone                0.8                0.2
cloprostenol Group    [+ or -] 0.1 (a)   [+ or -] 0.2 (b)

(a,b) The numbers with a different superscript for each row imply
significant differences (p [less than or equal to] 0.05). There
was no significant difference between both groups for each
variable of the same day.

Table 3. Average values ([+ or -] DS) of days until the
normalization of the clinical variables during the
evaluation of the pyometra treatment.

Treatment                 DS                 DP

Aglepristone       10.0               139.8
Group              [+ or -] 1.6 (a)   [+ or -] 17.8 (a)

Aglepristone       7.2                137.0
cloprostenol       [+ or -] 1.3 (b)   [+ or -] 17.7 (a)
Group

Treatment                DNE                DAV

Aglepristone       16.0               6.8
Group              [+ or -] 2.0 (a)   [+ or -] 1.9 (a)

Aglepristone       13.8               5.6
cloprostenol       [+ or -] 1.5 (a)   [+ or -] 0.5 (a)
Group

Treatment                DAP                DNA

Aglepristone       10.2               10.4
Group              [+ or -] 1.5 (a)   [+ or -] 1.1 (a)

Aglepristone       7.0                7.0
cloprostenol       [+ or -] 1.6 (b)   [+ or -] 1.0 (b)
Group

Treatment                DNA                DAPP

Aglepristone       7.8                5.6
Group              [+ or -] 1.3 (a)   [+ or -] 1.5 (a)

Aglepristone       5.0                5.6
cloprostenol       [+ or -] 1.0 (b)   [+ or -] 1.1 (a)
Group

DS: Days of secretion; DP: Days of proestrus DNE: Days to normal
echography; DAV: Days until absence of vomiting; DAP: Days until
the absence of pain; DNA: Days to normal activity; DNA: Days to
normal appetite; DAPP: Days until the absence of polydipsia/
polyuria.

(a, b) The numbers with a different superscript for each column
implies a significant difference (p [less than or equal to]
0.05).
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Title Annotation:SHORT COMMUNICATION
Author:Molina, Victor D.
Publication:Revista MVZ (Medicina Veterinaria y Zootecnia)
Date:May 1, 2015
Words:6672
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