Therapeutic responses for recovery of pyometra was recorded better in T
1 group (100%), followed by T
2 (71.43%) and T
C (42.86%). The repeated administration of prostaglandin analogues significantly increased the success rate at day 8 of treatment. The uterotonic action of prostaglandin analogues (dinoprost and misoprostol) lead to a faster decrease in the diameter of uterine lumen and its luteolytic action caused a faster drop in mean plasma progesterone concentration as compared to effect of non-hormonal therapeutic medication in animals. Among both prostaglandins, dinoprost showed the better therapeutic response in canine pyometra as compared to misoprostol treated animals. However, side effects of prostaglandin F
2α viz. vomiting, salivation, loose faeces, urination, ataxia, hyperpnoea and constriction or dilatation of pupil were seen similar to the previous report of
Jena et al., (2013). As described before, side effects may be reduced and eliminated by walking the dog after the injection of PGF
2α (Lopate, 2017).
All the characteristic clinical signs of pyometra like vaginal discharge, polydipsia, polyuria, depression and anorexia disappeared by day 8
th of therapy indicating complete clinical recovery. Further, recovery was accompanied by a gradual decrease in the diameter of the uterine lumen which became non-detectable ultrasonographically (Plate 3 and 4). The mean decrease in the diameter of the uterine lumen decreased gradually depends on treatment used (Table 1) which was significantly greater among days 0, 7 and 14 in bitches receiving the combined mifepristone-dinoprost treatment than in those treated with mifepristone-misoprostol and non-hormonal (100% versus 71.43% and 42.86%).
Effect of different treatment regimens on total uterine diameter and endometrium thickness in dogs affected with pyometra
On ultrasonographic examination, the mean total uterine diameter (mm) on day 0 was measured as 27.25±2.63 in T
1, 28.13±2.78 in T
2 and 29.40±3.62 in T
C treatment groups. There was significantly decrease in mean values of total uterine diameter in all the groups over the period of time from day 0 to day 14 (Plate 3 and 4). However, it decreased significantly (p<0.01) faster (on day 7) in both the hormonal treated groups (T
1 and T
2) as compared to non-hormonal treatment (T
c) group. Similar results on uterine diameter were also reported using different treatment in canine pyometra by Renukaradhya (2011) and
Meher et al., (2018). The several studies supporting the procedure adopted in this study for the confirmation of pyometra as the diagnosis of pyometra is best made with the aid of ultrasonography
(Bigliardi et al., 2004) and findings typically include an enlarged uterus with convoluted, tubular horns filled with anechoic to hypoechoic fluid (Plate 1)
(Fayrer-Hosken et al., 1991 and
Voges et al., 1996). The luminal contents are usually homogenous but contents may also be echodense with slow, swirling patterns (Nyland and Matton 2002).
A thickened endometrium with cystic structures is diagnostic for CEH (Plate 2) with or without pyometra
(Voges et al., 1996).
The mean endometrium thickness of uterus of pyometric dogs was measured by ultrasonography on day 0, 7 and 14 as shown in Plate 2. The mean values of endometrium thickness (mm) was ranged 4.13±0.84 to 6.04±0.95 before start of treatment (day 0) in all the groups. Later on it gradually decreased over the period of treatment (day 7 and 14) in all groups. In recovered animals, it was difficult to detect uterus so endometrium thickness couldn’t be measurable (<1 mm) in ultrasonography. The ultrasonographic aspect of a pathologically altered uterus varies but luminal fluid is commonly found and ultrasound is of great use to detect mild accumulation of fluid, even if differentiation of the type of fluid is not feasible (Pollard and Hecht, 2015).
All hematological parameters like total leukocyte count, neutrophil count, BUN, creatinine, Alanine aminotransferase (ALT), Alkaline phosphatase (ALP) and serum progesterone concentration elevated before treatment were decreased to normal range in completely recovered animals of different treatment groups (Table 2).
The mean TLC values (10
3/µl) recorded before initiation of treatment (day 0) were 34.81±2.73, 30.90±3.47 and 32.75±3.69, respectively in T
1, T
2 and T
C groups. These values were highly elevated as compared to the normal physiological range (6-17´10
3/µl). However, decrease in the mean TLC values after completion of treatment (day 8) were significantly decreased in T
1 and T
2 however, difference was statistically non significant in control group. There is availability of ample literature for support of the study. The comparable results of mean TLC values in canine pyometra were reported by Renukaradhya (2011) and
Melih et al., (2012) i.e. 24.05±59 to 51.24±80´10
3 per cmm and 38.53±7.28´10
3 per cmm, respectively. However, comparatively low TLC was found in the study of
Fransson et al., (2007) and
Hagman et al., (2006) who reported mean values of 22.6±13.5´10
3 per cmm; 23.31±11.45´10
3 per cmm, 22.8±11.4´10
3 per cmm, respectively.
The systemic effects of pyometra are reflected in the hemato-biochemical parameters of the animals. A characteristic change in the leukogram of the animal is noticed with significant increase in total leucocyte count
(Bigliardi et al., 2004). A common pathologic clinical finding in bitches with pyometra is a peripheral leukocytosis which is more pronounced in closed-cervix pyometra
(Gandotra et al., 1994). The marked leucocytosis observed in cases of pyometra is suggested to be due to bone marrow inflammatory response
(Sevelius et al., 1990) and diffused suppurative inflammation of uterus to combat the infection.
The mean neutrophils (%) on day 0 was recorded 80.17±1.59 in T
1, 76.96±1.40 in T
2 and 77.10±1.46 in T
C groups. The results are similar to previous reports of
Hoffmann et al., (2000), Trasch et al., (2003) and Fieni (2006). After treatment the mean values of neutrophils returned to normal physiological values in all treated groups
i.e., 67.86±0.96 in T
1, 69.76±0.73 in T
2 and 71.76±1.45 in T
C groups. The leucocytosis which is a predominant finding in the study is due to neutrophilia exhibited by most of the animals. Neutrophilia has also been reporded in several studies
(Hagman et al., 2006; Renukaradhya, 2011 and Arunima, 2013). It might be due to retention of purulent exudates in the uterus which exerts a chemotactic effect on neutrophils resulting into accelerated granulopoiesis
(Meher et al., 2018). The neutrophilia recorded in the present investigation may be attributed to the defense mechanism of the uterus in response to the invading microorganisms.
In present study BUN (15.93±2.33 mg/dl) in Dinoprost treated animals on day 8 was similar to the findings of
Shah et al., (2016) on day 14. The mean BUN value of control group (T
C) on day 8 was similar to that of
Jena et al., (2013). Renukaradhya (2011) and
Jena et al., (2013) reported comparatively low mean values of BUN (12.88±0.89 to 26.38±7.44 mg/dl) on day 0. In other study
Shah et al., (2016) had reported slight elevated mean values of BUN (46.01±3.29 to 46.69±1.43 mg/dl) on day 0. This variation may be due to individual variation in severity of case, age group and physio-pathological condition of multiple organs especially kidney.
Wheaton et al., (1989) concluded that elevated blood urea nitrogen level seen in some cases in their study was most often a result of pre renal uremia. The pre renal factors are those which lead to the lowering of glomerular filtration rate and impair the efficiency of kidneys. A gradual decrease in elevated blood urea nitrogen level during the course of treatment is indicative of positive response of the animal to the treatment and elimination of toxaemia in the affected bitches. This reversal of toxemia was consistent with other studies
(Verstegen et_al2008).
The mean creatinine value in this study decreased significantly on day 8 in hormonal treated groups. However, difference in control (T
C) group was statistically not significant. Similar results were also reported by Renukaradhya (2011). The present findings are in agreement with the findings of Lopate (2017) who also reported a slight increase in the creatinine level above the normal range in few animals in different treatment groups. It could be attributed to reduced renal perfusion relating to toxemia. The impairment of renal function along with other multiple organ dysfunctions is a frequent complication of pyometra
(Hiene et al., 2001 and Lopate, 2017). However, in some studies no significant variation in mean creatinine values in animals with pyometra in different treatment groups on day 0 and 8 was recorded and it remains in the normal physiological range (1-2 mg/dl) for clinically healthy dogs (Benjamin,1985).
The mean ALT value (IU/L) in pyometric animals before initiation of treatment in this study was recorded 69.53± 6.25, 60.50±7.07 and 52.20±8.23 respectively in T
1, T
2 and T
c groups. After completion of treatment on day 8, the mean ALT values was decreased in all groups. This indicates better recovery of cases. Similar range of ALT values after ovariohysterectomy in dogs was also recorded by
Patil et al., (2013). Lopate (2017) also reported that mild to moderate increase in serum alanine amino transaminase concentrations in animals occasionally encountered may be due to the hepato-cellular damage caused by septicemia and/or due to diminished hepatic circulation and cellular hypoxia in the dehydrated bitch which supports the findings of this study.
There is significantly decrease in mean values of ALP (IU/L) from day 0 to day 8 in T
1 and T
2 groups
i.e., 117.91±2.31 to 60.52±3.67 IU/L in T
1 group, 125.50±12.4 to 93.25±9.09 IU/L in T
2 group. The mean values of ALP in the present study before initiation of treatment were similar to that of study of
Shah et al., (2016) in pyometra affected dogs. Mifepristone and dinoprost treated animals showed similar findings (60.52±3.67 IU/L) of ALP after the treatment on day 8 and comparable to the findings of
Shah et al., (2016) using similar treatment protocol in canine pyometra. Non hormonal treated animals in the present study showed similar mean values of ALP on day 8 (after treatment) similar to finding of
Jena et al., (2013). There was a common tendency for decline in the serum ALP activity with initiation of different treatment regimens in canine pyometra. Sodikoff (1995) have stated that major causes of increased serum ALP activity in dogs are cholestatic liver diseases. These higher findings of ALP reflect hepato-cellular damage in response to toxemia or diminished hepatic circulation due to dehydration induced by pyometra
(Verstegen et al., 2008) as in the present study.
In the present study there was significantly decrease in mean serum progesterone in both the hormone treated (T
1 and T
2) groups. The higher pre-treatment mean values of serum progesterone concentration in the present study indicating presence of corpus luteum similar to reports of
Gupta et al., (2013). They also found higher serum progesterone in close pyometra than the open ones (19.97±2.88 vs 6.81±2.59 ng/ml) which was associated with presence of multiple cysts and 1-3 CLs simultaneously on the ovaries in bitches with close pyometra and only 1-2 CLs in open pyometra, since CL is the primary source of progesterone in circulation. In this study significantly decrease in serum progesterone post-treatment in antiprogestin and prostaglandin treated (T
1 and T
2) groups may be due to regression of corpus luteum. It reflects the results of the better recovery with low recurrence of cases after treatment in both the groups.
