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INFLAMMATION, INFECTION, OR BOTH? ROOT CAUSES OF ENDOMETRITIS


inflammatory mediators. The dose of firocoxib used in this studywas 0.2mg/kg as compared to themore com- monly used dose of 0.1mg/kg, once daily (after a single loading dose of 0.3mg/kg).28 Bacterial cell wall extracts have been investi-


gated regarding their effects on uterine immune system and enhancement of pregnancy rates. While the majority of work is focused on clearance and treatment of infectious endometritis, a study in 2012 evaluatedtheimmuneresponsetosperma- tozoa. Mares were treated with 1.5mg Settle IVa 24hours prior to insemination. Overall, a downreg- ulation of IL-1 messenger RNA was found in this population of susceptible mares 6hours after AI.22 Large-scale clinical trials showing alterations in pregnancy rates using bacterial cell wall extracts are limited in the treatment ofPMIE.


Mucolytics and Chemical Curettage


Not uncommonly, the lavage effluent from mares with PMIE contains excessive quantities of mucus.29 Chronic uterine inflammation often results in produc- tion of exuberant production ofmucus,whichmanifests as a thick mucus layer overlying the endometrium. Mucolytic agents such as N-acetylcysteine, or other agents focusing on stoppingmucous production, includ- ing dimethyl sulfoxide or kerosene, can be used with beneficial effects in some mares. N-acetylcysteine dis- rupts disulfide bonds in mucus, making it less viscous. Infusion of 3.3%N-acetylcysteine (30mL of a 20% solu- tion diluted in 150mL saline solution) has been associ- ated with an increase in pregnancy rates inmares that have excessivemucus accumulation.30 Infusion of a 30%solution of dimethyl sulfoxide into


the uterus results in improvement of biopsy grade, and treated mares tend to have an increased preg- nancy rate.31 Although intrauterine infusion of kero- sene is associated with a severe endometritis and necrosis of the luminal epithelium, 50% of treated mares with a category II or III biopsy score became pregnant on the subsequent cycle and carried foals to term.32 It is thought that the severe inflammation and necrosis results in removal of mucus and exudate from the uterine epithelium.32 Kerosene treatment typically consists of infusion of 50 to 500 mL of kero- sene undiluted into the uterus. Typically, lower vol- umes are used during diestrus and larger volumes during estrus to account for an open vs closed cervix. Uterine lavage and ecbolics are used 12 to 18hours later to remove residual kerosene and debris from the uterus.


3. Platelet-Rich Plasma


Platelet-rich plasma (PRP) is a filtrate of whole blood plasma with a high concentration of platelets. PRP contains various growth factors and cytokines that act in an anti-inflammatory manner throughout the body. This therapy has become common to reduce PMIE inflammation and fluid accumulation post- breeding.33–38 Common time points to use PRP are


48 and 24hours prior to breeding and 6 and 24hours postbreeding.


4. Summary


Multiple treatments have been utilized to treat PMIE in the horse. The clinician is faced with the challenge of how to select these treatment options in clinical practice. Overall, as the severity of PMIE increases, the treatments required to manage fluid retention and uterine inflammation are increased. The best approach to treating mares with PMIE is to obtain a thorough history, perform serial examinations, and optimize the treatment regimen for each, individual mare.


Acknowledgments


Declaration of Ethics The Author has adhered to the Principles of VeterinaryMedical Ethics of the AVMA.


Conflict of Interest The Author has no conflicts of interest.


References and Footnote


1. Traub-Dargatz JL, Salman MD, Voss JL. Medical problems of adult horses, as ranked by equine practitioners. J Am Vet Med Assoc 1991;198:1745–1747.


2. Troedsson MH, Loset K, Alghamdi AM, et al. Interaction between equine semen and the endometrium: The inflam- matory response to semen. Anim Reprod Sci 2001;68:273– 278.


4. Causey RC. Making sense of equine uterine infections: The many faces of physical clearance. Vet J 2006;172:405–421.


5. Samper J. Uterine edema in the mare. In: Samper J, ed. Equine Breeding Management and Artificial Insemination. St Louis, MO: Elsevier; 2009;133–138.


6. Betteridge K, Eaglesome M, Mitchell D, et al. Development of horse embryos up to twenty two days after ovulation: Observations on fresh specimens. J Anat 1982;135:191–209.


7. Neely DP, Kindahl H, Stabenfeldt GH, et al. Prostaglandin release patterns in the mare: Physiological, pathophysio- logical, and therapeutic responses. J Reprod Fert Supp 1979;27:181–189.


8. Scoggin CF. Not just a number: Effect of age on fertility, pregnancy and offspring vigour in Thoroughbred brood- mares. Reprod Fertil Dev 2015;27:872–879.


9. Woodward EM, Christoffersen M, Campos J, et al. Susceptibility to persistent breeding-induced endometri- tis in the mare: Relationship to endometrial biopsy score and age, and variations between seasons. Theriogenology 2012;78:495–501.


10. Canisso IF, Segabinazzi LGTM, Fedorka CE. Persistent breeding-induced endometritis in mares—a multifaceted challenge: From clinical aspects to immunopathogenesis and pathobiology. Int J Mol Sci 2020;21:1432.


11. Cadario ME, Thatcher WW, Klapstein E, et al. Dynamics of prostaglandin secretion, intrauterine fluid and uterine clear- ance in reproductively normal mares and mares with delayed uterine clearance. Theriogenology 1999;52:1181–1192.


12. Madill S, Troedsson MHT, Santschi EM, et al. Dose response effect of intramuscular oxytocin treatment on


AAEP PROCEEDINGS / Vol. 68 / 2022 39


3. Allen WE, Pycock JF. Cyclical accumulation of uterine fluid in mares with lowered resistance to endometritis. Vet Rec 1988;122:489–490.


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