Treatment of acute and chronic endometritis (Proceedings)
Correcting the defects in uterine defense, neutralizing virulent bacteria, and controlling post-breeding inflammation are the goals of successful therapy. This is accomplished by surgically correcting anatomical defects, improving physical drainage after insemination, reducing the length or modulating the inflammatory response to insemination and inhibiting bacterial growth. Post-breeding inflammation is most commonly treated by improving physical clearance of uterine fluid with uterine irrigation followed immediately by administration of either oxytocin (10-25 IU i.v. or i.m.) or cloprostenol (250 μg i.m.). In some cases, the uterus is infused with antibiotics post mating. Bacterial or fungal endometritis are routinely treated for 3 to 5 days during estrus with either intra-uterine or systemic antibiotics in combination with uterine irrigation. Emphasis here will be on the use of mucolytics, chelating agents and administration of steroids for modulating the inflammatory response.
Not all infections respond to uterine irrigation and antibiotic treatment. Treatment failure may be due to continual contamination of the uterus because of anatomical abnormalities in the caudal tract, degradation of antibiotic in uterine exudates, or biofilm production by the micro-organism. Previous work indicates that mucus secretion increases during experimental uterine inflammation, and in mares with delayed uterine clearance and bacterial endometritis. Mares with chronic endometritis have an increase in the thickness of the mucus ribbon overlying the endometrium, increased staining intensity of both intracellular and extracellular mucus, and epithelial cell loss. Excessive mucus or exudate can interfere with antibiotic penetration, can render aminoglycosides chemically inert or may interfere with sperm transport to the oviduct. Treatment with a mucolytic agent may help clear mucus and increase effectiveness of intra-uterine antibiotics. Solvents and mucolytic agents have been added to uterine irrigation fluids in an attempt to clear exudate, mucus or biofilm. Agents used include DMSO, kerosene and N-acetylcysteine. Each compound appears to have some beneficial effects. Barren mares (n = 16) infused with a 30% solution of DMSO after breeding tended to have higher pregnancy rates than mares infused with saline. Intrauterine DMSO therapy also resulted in a significant improvement in endometrial biopsy classification in 18 of 27 mares; whereas only 2 of 18 barren mares improved following intrauterine saline treatment. In contrast, intrauterine infusion of 50 ml of commercially available kerosene in 26 mares with varying degrees of endometrial pathology induced diffuse moderate to severe endometritis, severe diffuse edema and production of a serum-like exudates. Half of the mares exhibited mild to severe necrosis of luminal epithelium. Mares were subsequently bred on the next cycle and surprisingly, 50% of the mares with Category II or III biopsy scores carried foals until term. Although kerosene was associated with significant inflammatory changes, pregnancy may have been established because mucus and exudate were removed via destruction and necrosis of uterine epithelium.N-acetylcysteine (NAC) is a mucolytic agent that disrupts disulphide bonds between mucin polymers, thereby reducing the viscosity of mucus. In addition, NAC possesses antioxidant and possibly some antimicrobial properties. NAC has been used to treat respiratory diseases such as pneumonia, the pulmonary component of cystic fibrosis in humans, meconium impactions in both humans and equine neonates and meconium aspiration pneumonia in equine neonates. Multiple studies support its beneficial anti-oxidative properties especially in chronic inflammatory diseases. We have recently evaluated its effect on the endometrium and epithelium (Gores-Lindholm et al. 2009). Endometrial biopsies were obtained from 12 fertile and 10 barren mares before and after infusion of a 3.3% solution of N-acetylcysteine (day 1) and compared to biopsies obtained from mares infused with saline. The uterus of all mares was irrigated with 2 L of lactated Ringer's solution on days 2 and 3 and a second biopsy obtained. Endometrial biopsies were given a Kenney grade by a board certified veterinary pathologist and changes in epithelial architecture and mucus blanket were measured by image analysis. Data indicated that NAC was not harmful to the endometrium and that it may counteract the irritating effect of saline, as reflected through increased cell height in control mares. As further evidence that NAC does no harm and may be beneficial, 20 Thoroughbred mares each bred 2 to 5 times in 2007 or 2008 and with a history of endometritis were mated naturally to commercial stallions in Central Kentucky in late May and June 2008. Mares received a 0.6% solution of ACE either the treatment cycle before (n = 10) or in the 48 h before breeding (n = 10) in addition to conventional treatments. Infusion before breeding was associated with higher than expected pregnancy rates as 17 of 20 mares (85%) conceived and foaled in 2009. Before this study, the rationale for using NAC as a uterine infusion had been the removal of inspissated secretions, exudate and biofilm, (i.e. as a mucolytic). However, since increased vaginal mucus viscosity is documented to inhibit sperm forward progression in cows, it is also speculated that NAC may improve sperm-transport in mares with excessively viscous mucous secretions by breaking the cross-linking disulfide bridges between mucin polymers.