Therapeutic efficacy of natural prostaglandin in the treatment of pyometra in bitches
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1 Therapeutic efficacy of natural prostaglandin in e treatment of pyometra in bitches Basanti Jena, K. Sadasiva Rao, K. C. S. Reddy and K. B. P. Raghavender College of Veterinary Science, Sri Venkateshwara Veterinary University, Rajendranagar, Hyderabad, Andhra Pradesh, India Corresponding auor: Basanti Jena, drbasantijena@gmail.com Received: , Accepted: , Published online: How to cite is article: Jena B, Rao KS, Reddy KCS and Raghavender KBP (013) Therapeutic efficacy of natural prostaglandin in e treatment of pyometra in bitches, Vet. World 6(6):95-99, doi: /vetworld Abstract Aim: The current study was done to study e erapeutic effect of natural prostaglandin in treatment of canine pyometra. Materials and Meods: Seven bitches were treated wi natural PGFα i.e. dinoprost tromeamine at e dose rate of 100 µg/kg body weight subcutaneously once daily for 7 days wi supportive erapies. The physiological, haematological and biochemical parameters were studied before (0 day) and after treatment (8 day). Therapeutic efficacy was assessed in terms of return of abnormal parameters to eier normal or near normal value as compared to e untreated control group, intensity of side effects and post treatment reproductive status. Results: All physiological, haematological and biochemical parameters in e seven treated bitches returned to normal range at e end of treatment. The intensity of side effects was quite severe in e treatment group. Six bitches came to estrus wiin mons of treatment and out of em four conceived on subsequent mating. In rest ree bitches ere was recurrence of pyometra wiin 4 mons of treatment. Conclusion: Though conception rate of recovered bitches is decreased when compared wi at of normal healy bitches still is treatment protocol can be used successfully in treatment of canine pyometra to conserve e breeding capability of bitches. Keywords: bitch, prostaglandin, pyometra, erapeutic efficacy Introduction dins, repeated doses are required to cause luteal regression. Administration of prostaglandins caused significant adverse effects including salivation, vomiting, straining, diarrhoea, pyrexia and occasionally respi- ratory distress [7]. Immediate breeding of e treated bitches during e estrus is recommended to prevent e recurrence [8]. Fertility of recovered bitches is decreased when compared wi at of normal, untreated bitches [9]. Though several literatures are available on use of natural prostaglandin in treatment of pyometra but e previous researches depict controversial findings. So e current study was done to study e erapeutic effect of natural prostaglandin in treatment of canine pyometra. Pyometra is e accumulation of purulent material occurred wiin e lumen of e uterus in intact bitches [1] which was reported to induce high mortality in bitches if not treated []. It is recognized as one of e main causes of disease and dea in e bitch [3]. It is a common disease in countries where routine spaying of young dogs is not common practice [4]. In most cases, e treatment of choice is ovariohysterectomy, but surgery is a radical form of treatment at prevents any furer reproduction. In order to conserve e breeding capability of valuable females, medical treatment can be attempted which usually involved e repeated administration of prostaglandins [5, 6] which causes lysis of e corpora lutea and a reduction in plasma progesterone concentration. Low progesterone level, furer causes relaxation (opening) of e cervix, allow expulsion of e uterine content resulting in reduction in uterine secretions and increased uterine contractions. In addition, prostaglandins have a uterine spasmogenic action which results in e expulsion of uterine fluid. As corpora lutea of bitches are relatively insensitive to e effects of administered prostaglan- This article is an open access article licensed under e terms of e Creative Commons Attribution License ( org/licenses/by/.0) which permits unrestricted use, distribution and reproduction in any medium, provided e work is properly cited. Materials and Meods The present work was carried out at Department of Animal Reproduction, Gynaecology and Obstetrics, College of Veterinary Science, Rajendranagar, Hyderabad. Fourteen clinical cases of different breeds in e age group of one to twelve years at were brought to e Animal Reproduction, Gynaecology and Obstetrics Unit, Teaching Veterinary Clinical Complex, Bhoiguda and Campus Hospital, College of Veterinary Science, Rajendranagar, Hyderabad wi known breeding history or having clinical symptoms 95
2 Table-1. Physiological, haematological and biochemical parameters Parameters Group I Group II Before treatment After treatment P value Before treatment After treatment P value (0 day) (8 day) (0 day) (8 day) Physiological parameters 0 Rectal temperature ( F) 10.83± ± ± ± Heart rate (per minute) 11.00± ± ± ± Respiration rate (per minute) 9.57± ± ± ± * Haematological parameters Haemoglobin (gram %) 11.0± ± ± ± PCV (%) 33.83± ± ± ± TEC ( 10 /µl) 5.48± ± ± ± MCV (fl) 66.88± ± ± ± MCH (pg) 1.44± ± ± ± MCHC (%) 31.48± ± ± ± TLC ( 10 /µl) 33.7± ± ± ± Neutrophil (%) 76.86± ± ± ± * * Lymphocyte (%) 11.14± ± ± ± Monocyte (%) 9.86± ± ± ± Eosinophil (%).14± ± ± ± Biochemical parameters BUN (mg/dl) 6.8± ± ± ± Creatinine (mg/dl).10± ± ± ± * * AST (U/L) 49.14± ± ± ± ALT (U/L) 8.8± ± ± ± ALP (U/L) ± ± ± ± TP (g/dl) 7.94± ± ± ± Albumin (g/dl).91± ± ± ± Globulin (g/dl) 5.03± ± ± ± * Total Bilirubin (mg/dl) 0.46± ± ± ± NS; - Not significant, *; - Significant (P<0.05), **; - Significant (P<0.01) suspected for open type of pyometra which was furer confirmed by using diagnostic meods like abdominal palpation, radiography and ultrasound examination were taken for e study. Bitches were divided into two groups each consisting of seven bitches and subjected to different treatment protocols. Group I bitches were treated only wi supportive erapies (control group). Bitches in Group II, were treated wi natural PGFα i.e. dinoprost tromeamine at e dose rate of 100 µg/kg body weight subcutaneously once daily for 7 days wi supportive erapies. The physiological, haematological and biochemical parameters were studied before (0 day) and after treatment (8 day). Attempts were made to contact e owners of e bitches at recovered after various treatments to obtain e follow up data. All e data pertaining to post treatment return to estrus, breeding, conception and recurrence were made. Therapeutic efficacy was assessed in terms of return of abnormal parameters to eier normal or near normal value as compared to e untreated control group, intensity of side effects and post treatment reproductive status. All bitches of control group and recurred bitches had undergone ovariohysterectomy. The results of e study were recorded and statistically analyzed as per e meods suggested by Snedecor and Cochran [10]. Analysis of variance was done to find out e significant difference between e physiological, haematological and biochemical parameters before and after treatment in different groups. Results Treatment response: All e seven bitches were successfully treated by using natural PGFα (Dinoprost tromeamine) at e dose rate of 100 µg/kg body weight once daily for 7 days subcutaneously along wi supportive erapy (100 per cent recovery rate) which resulted in disappearance of externally visible clinical signs of pyometra. Bitches became active and alert by 8 day of treatment. There was total ceasation of vaginal discharge wi little or no palpable evidence of enlargement of uterus which was confirmed by abdominal radiography and ultrasonography. Normal rectal temperature, respiration rate wi an improved appetite were observed at end of treatment at is presented in Table-1. The recovery rate was 100 per cent in e treated group. There was significant increase in mean haemoglobin, packed cell volume and total eryrocyte count level (P<0.05) indicating resolution of anaemia on day 8 as compared to control group bitches. There was significant decrease in mean total leucocyte count (P<0.05), neutrophil count and monocyte count level (P<0.01) wi increase in lymphocyte count as compared to control group bitches resulting in normal blood picture in all e treated bitches on 8 day of observation which is reported in Table-1. There was significant decrease in blood urea nitrogen (P<0.05), creatinine (P<0.01), aspartate transaminase (P<0.01), alkaline phosphatase (P< 0.05), mean total protein (P<0.05) and globulin level in serum (P<0.01) on 8 day of observation as compared to control group bitches. There was significant increase in mean alanine transaminase level (P<0.05) as compared to control group bitches resulting in normal serum biochemistry in all e treated bitches on 8 day of observation which is represented in Table-1. Oer physiological, haematological and biochemical parameters did not show any significant change following treatment wi PGFα as compared to control 96
3 eously. The side effects observed were vomition (6/7, 85.71%), panting (6/7, 85.71%), restlessness (7/7, 100%), hyperpnoea (7/7, 100%), defaecation (5/7, 71.43%) and urination (5/7, 71.43%). The reactions started wiin few minutes after PGFα administration and disappeared wiin 1 to 1.5 hours. doi: /vetworld group bitches. All data pertaining to physiological, observation. These findings were in agreement wi e haematological and biochemical parameters of control previous reports of treatment of pyometra using natural group and treatment group has been represented in e PGFα for at e dose rate of 50 µg/kg/day for 5 days Table-1. [16]. All e above effects might be due to effect of Side effects: In is present study several physical PGF reactions were observed in group II bitches which were α exerted on uterine myometrium, cervix and subjected to natural PGF α (Dinoprost tromeamine) corpora lutea. PGFα stimulated uterine motility. This at e dose rate of 100 µg/kg body weight subcutan- myotonic effect increased intrauterine pressure to cause movement of uterine contents towards e cervix. The contractile effect of PGFα on myometrium, gastrointestinal tract, tracheobronchial and bladder smoo musculature accounts for e clinical responses observed and reflects e physiologic effects of endogenous prostaglandins [13]. PGFα offers e advantage of a double action i.e. myocntractile and Recurrence: Though complete clinical recovery was luteolytic [17]. Clinical recovery after treatment wi observed in all e bitches after treatment, in ree natural PGFα might be due to its effect on uterine bitches ere was recurrence of pyometra wiin 4 myometrium, cervix and corpra lutea. It caused mons of treatment. Out of e ree bitches, one contraction of myometrium and relaxation of cervix recurred wiin one mon of treatment. Recurrence which resulted in expulsion of e exudates from e rate was 4.85 per cent in is group of bitches. uterus. Lysis of e corpora lutea (or) transitory In all e recurred bitches ere was presence of inhibition of luteal steroidogenesis also resulted from all classical clinical signs of pyometra like vaginal administration of PGFα. These actions were discharge, polydipsia, polyuria, leargy and anorexia. particularly dependent on e dosage, route and All physiological, haematological and biochemical frequency of administration and timing of PGFα parameters shifted towards an abnormal level erapy wiin e luteal phase. The resultant decreased simulating to e condition observed just before plasma progesterone concentration reduced e treatment. Abdominal palpation revealed palpable stimulus for endometrial grow and glandular uterus which was furer confirmed by radiography or secretions resulting in resolving e vaginal discharge ultrasonography revealing accumulation of purulent and oer clinical signs [8]. exudates in uterus. The intensity of side effects were quite severe in Post treatment reproductive status: After complete treatment group which might be due to higher dose of clinical recovery of all e bitches in dinoprost natural PGFα (Dinoprost tromeamine) used for e tromeamine treated group, six bitches (85.71%) treatment [8,13,18,19]. Side effects were dose- came to estrus wiin mons of treatment which dependent [17] and were known to diminish wi were subsequently mated. Out of em four bitches repetition of treatment [15]. Though all e above conceived as confirmed by ultrasonography resulting auors had reported salivation as e most common in per cent conception rate in e treated group. side effect observed after PGFα erapy, in e present study it was not observed might be due to e Discussion administration of Atropine sulphate minutes All e animals in e treated group recovered prior to administration of PGFα [0]. Attempts were after completion of treatment protocol which is similar made to minimise e side effects by wiholding food to e previous findings [11-13]. However, per and water supplied to e bitches 4-6 hours prior to cent recovery rate was reported by using Dinoprost administration of PGFα, use of Atropine sulphate and tromeamine for treatment of canine pyometra in providing mild walk to bitches after PGFα injection in some study [14]. Natural prostaglandin is preferable to order to facilitate early metabolism and excretion of prostaglandin analogues, as it not only induced PGFα end product [5,1]. However, use of natural substantial luteolysis, but also resulted in more PGFα at a dose of 0 µg/kg body weight [11] and 30 substantial uterine contractions [15]. There was µg/kg body weight [1] in repeated doses daily for significant change in haematological parameters in e treatment of canine pyometra showed no adverse side treatment group as compared to control group bitches effects which might be due to e lower dose used. resulting in normal blood picture in all e treated In e present study recurrence rate was in bitches on 8 day of observation. These findings were accordance wi e previous reports of 40 per cent [5]. in accordance wi e previous reports [5,11,14]. At e time of relapse of e disease ere were again There was significant change in biochemical e typically raised AST, decreased ALT and increased parameters in e treatment group as compared to AST/ALT [16]. However, in contrary to e present control group bitches resulting in normal serum report, it has been reported at ere was no recurrence biochemistry in all e treated bitches on 8 day of of pyometra wiin 10 mons [11], 1 mons [14] and 97
4 6 mons [18] of observation period. Immediate first auor. All auors contributed equally in e breeding of e treated bitches during e estrus is whole research work as well as in e preparation of recommended to prevent e recurrence [8]. manuscript. All auors read and approved e final Prostaglandin treatment did not eliminate e disease, manuscript. but only reduced it to a subclinical level. Deep-seated Acknowledgements infection could remain until next diestrus, when e plasma progesterone concentration became high as in The auors are ankful to Sri Venkateswara pregnancy. Uterine defence mechanisms were Veterinary University, Tirupati for giving an inhibited by progesterone during diestrus in e bitches opportunity to do e research. We wish to extend our so at infection could become clinically apparent at anks to e Dean, College of Veterinary Science, is time. Hence recurrences were most common Rajendranagar, Hyderabad for providing all e during diestrus. As long term recurrence rate was high, facilities to complete e research successfully. prostaglandin treatment was not recommended for Competing interests bitches where pregnancy was undesirable or improbable. In such bitches it might be useful only in Auors declare at ey have no competing interest. temporarily decreasing severity of clinical signs. In References bitches wi a favourable short-term response to 1. Pretzer S. D. (008) Clinical presentation of canine treatment it would seem too prudent to breed at first pyometra and mucometra: A review, Theriogenology, 70 : post treatment estrus. Since pyometra might recur as late as 7 mons after treatment, it was unlikely at. Singh K. P., Singh B., Singh J. P., Singh S. V., Singh P. and Singh H. N. (010) Diagnostic and erapeutic postponement of breeding would be more successful management of pyometra in bitches, Intas Polivet, 11 : 86- [5]. Though several auors had reported use of second 87. series of PGFα erapy in e bitches affected wi 3. Coggan J. A., Melville P. A., Oliveira C. M., Faustino M., pyometra [13, ], but in e present study it was not Moreno A. M. and Benites N. R. (008) Microbiological and histopaological aspects of canine pyometra, Brazilian practised due to owners' concern. All e recurred Journal of Microbiology, 39 : bitches had undergone ovariohysterectomy. 4. Pelander L., Hagman R. and Häggström J. (008) The conception rate in e present study was in Concentrations of cardiac Troponin I before and after accordance wi e previous finding where it has been ovariohysterectomy in 46 female dogs wi pyometra, Acta reported at expected conception rate varied from Veterinaria Scandinavica, 50: Meyers-Wallen V. N., Goldschmidt M. H. and Flickinger G per cent depending on e age of e animal, L. (1986) Prostaglandin Fα treatment of canine pyometra, wi fertility generally being highest in younger Journal of American Veterinary Medical Association, 189 : animals [19]. After breeding all e bitches in first estrus after treatment wi dinoprost tromeamine, 6. Renton J. P., Boyd J. S. and Harvey M. J. A. (1993) Observations on e treatment and diagnosis of open four out of e 10 bitches (40%) reproduced wiin one pyometra in e bitch (Canis familiaris), Journal of year [5]. However, it has also been reported at e Reproduction and Fertility Supplement, 47 : conception rate of e bitches in which estrus had 7. Hubler M., Arnold S., Casal M., Fluckiger M., Hauser B., returned was 83.3 per cent [14] which was higher an Corboz L. and Rusch P. (1991) Use of a low dose e report of e present study. prostaglandin F alpha in bitches, Schweizer Archiv für Tierheilkunde, 133 : (Abst). Conclusion 8. Nelson R. W., Feldman E. C. and Stabenfeldt G. H. (198) Treatment of canine pyometra and endometritis wi All e seven bitches were successfully treated by prostaglandin Fα, Journal of American Veterinary Medical using natural PGFα (Dinoprost tromeamine) at e Association, 181 : dose rate of 100 µg/kg body weight once daily for 7 9. Gobello C., Castex G., Klima L., Rodrıguez R. and Corrada Y. (003) A study of two protocols combining aglepristone days subcutaneously along wi supportive erapy and cloprostenol to treat open cervix pyometra in e bitch, wi all physiological, haematological and biochemical Theriogenology, 60 : parameters returning to normal range. This was furer 10. Snedecor G. W. and Cochran W. G. (1994) Statistical confirmed by using ultrasonography which revealed Meods. 8 Edn. Iowa State University Press, USA. 11. Arnold S., Hubler M., Casal M., Fairburn A., Baumann D., uterus eier invisible or difficult to visualise. The Flueckiger M. and Ruesch P. (1988) Use of low dose intensity of side effects were quite severe might be due prostaglandin for treatment of canine pyometra, Journal of to higher dose of natural PGFα (Dinoprost Small Animal Practice, 9 : tromeamine) used for e treatment. Three bitches 1. Sridevi P., Balasubramanian S., Devanaan T. G. and Pattabiraman S. R. (000) Low dose prostaglandin F alpha showed recurrence of pyometra wiin 4 mons of erapy in treatment of canine pyometra, Indian Vet. J, 77 : treatment. As conception rate was at optimum level is protocol can be successfully tried in treatment of 13. Pande N., Prabhakar S., Gandotra V. K., Nanda A. S. and canine pyometra where e breeding capability of e Singla V. K. (004) Comparative efficacy of parenteral and animal is desired to be conserved. intravaginal administration of PGFα for treatment of pyometra in bitches, Indian Journal of Animal Reproduction, Auors contribution 5 : This article is e part of MVSc research work of e 14. 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5 pyometra by inoculation of Escherichia coli into e uterus canine pyometra complex, Indian Vet. J., 73 : and its relationship to reproductive features, Animal 19. Smi F. O. (006) Canine pyometra, Theriogenology, 66 : Reproduction Science, 87 : Verstegen J., Dhaliwal G., Onclin K. V. (008) Mucometra, 0. Lein D. H., Concannon P. W., Hornbuckle W. E., Gilbert R. cystic endometrial hyperplasia, and pyometra in e bitch: A., Glendening J. R. and Dunlap H. L. (1989) Termination Advances in treatment and assessment of future reproductive of pregnancy in bitches by administration of Prostaglandin success, Theriogenology, 70 : Fα, Journal of Reproduction and Fertility Supplement, 39 : 16. Schepper J. D., Stock J. V. D. and Capiau E. (1987) The characteristic pattern of Aspartate Amino Transferase and 1. Reddy K. R. C., Rao K. S., Raju K. G. S., Raghavender K. B. Alanine Amino Transferase in e bitch wi e cystic P. and Reddy A. G. (010) Therapeutic efficacy of hyperplasia pyometra Complex: effect of medical or surgical Mifepristone, cabergoline and cloprostenol for termination treatment, Veterinary research communications, 11 : of pregnanacy in bitches, Indian Journal of Animal 17. Romagnoli S. (008) Reproduction: How I treat pyometra, Reproduction, 31 : 19-. Proceedings of e Souern European Veterinary Congress. Feldman E. C. and Nelson R. W. (1996) Cystic Endometrial and Congreso Naciona AVEPA, Barcelona, Spain. Hyperplasia and Pyometra Complex, Canine and Feline 18. Pawde A. M. and Kumar H. (1996) Medical management of nd Endocrinology and Reproduction, Edn. pp ******** 99
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