Topic:Prostaglandins
Prostaglandins are lipid compounds derived from fatty acids that are present in various tissues of horses. They are involved in a wide range of physiological processes, including the regulation of inflammation, blood flow, and reproductive functions. In equine medicine, prostaglandins are often studied for their role in modulating inflammatory responses and their potential therapeutic applications. These compounds can influence pain perception and are involved in processes such as parturition and the estrous cycle in mares. This page collects peer-reviewed research studies and scholarly articles that explore the synthesis, function, and clinical applications of prostaglandins in equine health.
Role of progesterone in mobility, fixation, orientation, and survival of the equine embryonic vesicle. Luteal progesterone was removed by an injection of prostaglandin F2alpha or bilateral ovariectomy on Day 12 of pregnancy in pony mares. The embryonic vesicle remained mobile in the uterus until loss occurred on Days 13, 13, 15, or 19 in four prostaglandin-treated mares and Days 15, 17, 19, or 26 in four ovariectomized mares. Exogenous progesterone given daily, starting on Day 12, maintained pregnancy until Day 40 in five of five prostaglandin-treated and three of four ovariectomized mares. During two-hour mobility trials on Day 14, embryonic vesicles in mares without luteal or exogenous proges...
Effect of Salmonella typhimurium endotoxin on PGF-2 alpha release and fetal death in the mare. The infusion of Salmonella typhimurium endotoxin into pregnant mares resulted in a biphasic release pattern of PGF-2 alpha as determined by 15-keto-13,14-dihydro-PGF-2 alpha concentrations. The initial phase of 1 h duration was followed by accentuated release by 2 h after infusion; concentrations reached basal levels by 6 h. In 7 mares at 23, 26, 29, 33, 36, 53 and 55 days of gestation, fetal death occurred between 36 and 120 h after infusion; 12 mares at 46, 51, 56, 59, 65, 71, 73, 85, 103, 138, 283 and 318 days of gestation did not abort after endotoxin infusion. Luteal activity was compromi...
Endotoxin-induced hemodynamic and prostaglandin changes in ponies: effects of flunixin meglumine, dexamethasone, and prednisolone. Shock was induced in four groups of anesthetized ponies with an intravenous injection of Escherichia coli endotoxin [125 micrograms/kg]. Five minutes after endotoxin injection, the ponies were given no treatment (group A), flunixin meglumine (FM:1.1 mg/kg) (group B), dexamethasone (2 mg/kg) (group C), or prednisolone (10 mg/kg) (group D). Additionally, FM was given every 3 hours, and the steroids were given at 3, 9, and 24 hours following endotoxin. Hemodynamic measurements were made during the 4-hour anesthetic period. Blood samples were collected for the analysis of prostaglandins, blood che...
PGF-2 alpha release, progesterone secretion and conceptus growth associated with successful and unsuccessful transcervical embryo transfer and reinsertion in the mare. The outcome of 23 collections and reinsertions of conceptuses on Days 10.5-13.5, 4 transfers of Day-10.5, and 13 transfers of Day-6.5 embryos (ovulation = Day 0) was monitored in 30 mares. Blood samples were taken before and after each procedure to measure plasma 15-keto-13,14-dihydroprostaglandin F-2 alpha (PGFM), and then daily for progesterone determinations. Mares were also subjected to daily teasing for detection of oestrus, and to uterine ultrasonography for tracing the development of the conceptus. After the reinsertions, 12/23 conceptuses were detectable immediately after the procedure...
Induction of ovulation in cyclic mares by administration of a synthetic prostaglandin, fenprostalene, during oestrus. Fenprostalene (250 micrograms) or saline was given at 60 h after the onset of oestrus in alternate oestrous periods to 8 mares for 4 cycles. Onset of oestrus and stage of cycle were determined by daily teasing, palpation and ultrasonography until time of treatment when follicular development was monitored at 12-h intervals to confirm ovulation. Serum progesterone concentrations were monitored daily. The interval from treatment to ovulation was significantly decreased (41.25 vs 73.50 h; P = 0.001) as was the duration of oestrus (5.63 vs 6.88 days; P = 0.005). There was no significant difference...
Use of a novel non-steroidal anti-inflammatory drug in the horse. In a two-part cross-over experiment in six ponies, an acute inflammatory reaction was generated by injecting carrageenin solution into subcutaneously-implanted tissue-cages lined with fibrovascular granulation tissue. In each part of the cross-over, half of the ponies received a novel phenylpyrazoline anti-inflammatory agent (BW540C) orally and half received a placebo treatment. BW540C inhibited platelet cyclo-oxygenase for 24 h but the reductions in exudate eicosanoid concentrations were less pronounced. A significant suppression in the rise of surface skin temperature in BW540C-treated ponie...
Concentrations of uterine luminal prostaglandins in mares with acute and persistent endometritis. Intrauterine infusion of 1 per cent oyster glycogen solution was used to induce acute endometritis in four genitally normal mares. Numbers of viable neutrophils recovered in uterine washings had increased by 1 h after infusion and remained elevated for at least 72 h. There was a significant correlation between numbers of viable neutrophils and total protein concentrations and between prostaglandin (PG)F and PGE2 concentrations in washings. There was also a significant relationship between concentrations of 15-keto-13, 14-dihydro PGF2 alpha in plasma and PGF in washings. Intrauterine concentrat...
Comparison of equine pituitary extract and follicle stimulating hormone for superovulating mares. Sixty light-horse, nonlactating mares were used to compare the efficacy of equine pituitary extract versus follicle stimulating hormone (FSH-P) for inducing multiple ovulations. On Day 12 of diestrus, mares were assigned to receive 1) no treatment, controls; 2) subcutaneous injections of 750 Fevold rat units of equine pituitary extract once daily; or 3) intramuscular injection of 150 mg of FSH-P twice daily. Ultrasound was used twice daily to visualize follicular changes and ovulation. For mares in Groups 2 and 3, treatment was initiated when two or more follicles > 20 mm were detected, and...
Effects of a phenylbutazone paste in ponies: model of acute nonimmune inflammation. In a 12-day treatment schedule, 5 ponies were given orally a paste formulation of phenylbutazone (PBZ) and 5 matched ponies were given equivalent doses of a placebo paste. On day 12, a mild, nonimmune inflammatory reaction was induced subcutaneously in the neck of each pony by inserting sterile, polyester sponge strips soaked in a 2% carrageenan solution. Exudate was collected at 4, 8, 12, and 24 hours by serial removal of sponges. There were no significant (P less than 0.05) differences in exudate protein concentration and leukocyte numbers between the treatment groups, but the group given PB...
Behavior and viability of the premature neonatal foal after induced parturition. Parturition was induced in 2 groups of mares, less than 300 (n = 49) and 300 to 320 days gestation (n = 31), by the administration of prostaglandin F2 alpha or fluprostenol and oxytocin. Foals were categorized into 4 groups according to their ability to adapt in, and survive, the neonatal period. Group A had no demonstrable coordinating reflexes, were weak from birth, and all died within 90 minutes. Group B had some righting reflexes, but had poor coordination and a weak suck reflex. They showed some improvement for about 2 hours, but all died within 9 hours. Group C foals had a good suck refl...
Role of conceptus secretory products in establishment of pregnancy. Conceptuses produce steroids, prostaglandins, proteins and possibly other unidentified agents which may play a role in the establishment and maintenance of pregnancy. A key event in this process is protection of the corpus luteum (CL) from the luteolytic activity of prostaglandin (PG) F-2 alpha of uterine origin. Oestrogens produced by the pig conceptuses between Days 11 and 16 appear to exert an antiluteolytic effect resulting in the sequestering of PGF-2 alpha within the uterine lumen. Failure of the pregnant uterus to release PGF-2 alpha in an endocrine fashion, therefore, allows for mainte...
Effects of flunixin meglumine, phenylbutazone and a selective thromboxane synthetase inhibitor (UK-38,485) on thromboxane and prostacyclin production in healthy horses. The efficacy of three agents which alter the metabolism of arachidonic acid was investigated in normal, conscious horses. A dose response evaluation was made of flunixin meglumine and phenylbutazone, two cyclo-oxygenase inhibitors, and of a selective thromboxane synthetase inhibitor, UK-38,485. Radioimmunoassay of thromboxane B2 (TxB2) and 6-keto prostaglandin F1 alpha (PGF1 alpha) was used to assess the concentrations of thromboxane A2 (TxA2) and prostacyclin (PGI2) respectively, in serum. Flunixin was the most potent inhibitor of serum TxB2 and 6-keto PGF1 alpha production. UK-38,485 also de...
Renal toxicity of non-steroidal anti-inflammatory drugs. Non-steroidal anti-inflammatory drugs represent the most heavily prescribed and used class of drugs in human medicine. Most are derivatives of either salicylates, propionic acid, indoleacetic acid, anthranilic acid, pyrazolone, or oxicams. They depress the synthesis of prostaglandins from arachidonic acid by reversible inhibition of the enzyme cyclooxygenase. In the kidney, prostaglandins PGE2 and PGI2 modulate the vasoconstrictor effects of angiotensin II, norepinephrine, and vasopressin. In the presence of volume contraction, anesthesia, or disease states associated with high levels of these...
Modulation of arachidonic acid metabolism in endotoxic horses: comparison of flunixin meglumine, phenylbutazone, and a selective thromboxane synthetase inhibitor. Two cyclooxygenase inhibitors (flunixin meglumine and phenylbutazone) and a selective thromboxane synthetase inhibitor were assessed in the management of experimental equine endotoxemia. Drugs or saline solution were administered to 16 horses 15 minutes before administration of a sublethal dose of endotoxin (Escherichia coli 055:B5). Plasma concentrations of thromboxane B2 (TxB2), prostacyclin (6-keto PGF1 alpha), plasma lactate, and hematologic values and clinical appearance were monitored for 3 hours after endotoxin administration. Pretreatment with flunixin meglumine (1 mg/kg of body weight...
Interrelationships between uterus and conceptus to maintain corpus luteum function in early pregnancy: sheep, cattle, pigs and horses. Processes associated with "Maternal Recognition of Pregnancy" are reviewed extensively from the ovine, bovine, porcine and equine species. Comparisons among these species indicate that CL maintenance is achieved primarily by a predominant antiluteolytic-anti PGF effect, and there is strong evidence for antiluteolytic-luteoprotective and luteotropic controls that complement this basic system. The nature of the chemical signals (steroids, prostaglandins and proteins) to regulate these processes among the species are described. Common to all of the species reviewed is a change in vascular dynamic...
Flunixin meglumine given in small doses: pharmacokinetics and prostaglandin inhibition in healthy horses. The pharmacokinetics and inhibition of prostaglandin synthesis in conscious horses given various dosages of flunixin meglumine were studied. Plasma concentrations of flunixin were measured by high-performance liquid chromatography, and serum thromboxane B2 and 6-keto prostaglandin F1 alpha were quantitated by radioimmunoassay. Within the dosage range studied, linear pharmacokinetics were achieved. After IV administration of flunixin (1.1 mg/kg, 0.25 mg/kg, 0.1 mg/kg), significant suppression of serum thromboxane generation persisted for 12, 4, and 3 hours, respectively. Repeated administration...
Experimentally induced phenylbutazone toxicosis in ponies: description of the syndrome and its prevention with synthetic prostaglandin E2. Phenylbutazone (PBZ) toxicosis was induced in 9 ponies to further define the clinical and pathologic changes occurring with this syndrome. Six additional ponies were treated with PBZ and a synthetic prostaglandin E2 to determine the role of prostaglandins in the pathogenesis of PBZ toxicosis. Ponies given only PBZ exhibited CNS depression, anorexia, weight loss, diarrhea, cyanotic mucous membranes, and oral ulcers. Total serum protein concentration gradually decreased during the 10-day treatment period. Marked mucosal atrophy, focal erosions, and ulcers characterized the lesions in the aliment...
Embryonic loss in mares: Nature of loss after experimental induction by ovariectomy or prostaglandin F(2alpha). Twenty-one pregnant pony mares were assigned to one of the following groups: 1) controls, 2) ovariectomy at Day 12, 3) ovariectomy at Day 12 plus daily progesterone treatment on Days 12 to 40, 4) PGF(2alpha) on Day 12, 5) PGF(2alpha) on Day 21, and 6) PGF(2alpha) on Day 30. Based on daily examinations by ultrasound, the embryonic vesicle was maintained to Day 40 in all control mares and in mares that were ovariectomized on Day 12 and given progesterone. The embryonic vesicle was lost in all mares of the other four groups. Administration of progesterone prevented the embryonic loss associated w...
Enhanced prostacyclin biosynthesis and decreased thromboxane formation by 3-dimethylamino 5-(2′,6′-dichlorobenzylidene) 6-methyl (4H)-pyridazine (PC 89). The effects of 3-dimethylamino 5-(2',6'-dichlorobenzylidene) 6-methyl (4H)-pyridazine (PC 89) on the biosynthesis of PG I2 and TX A2 using horse aorta and horse platelet microsomes as sources of enzymes and arachidonic acid as substrate, were investigated. PC 89 (1.10(-6) M- 1.10(-3) M) dose-dependently - enhanced the biosynthesis of PG I2: the AD50 was 6.8 X 10(-6) M +/- 1.2 X 10(-9) M, the Vmax did not vary significantly with concentrations: PC 89 increased the affinity of enzyme for substrate - but inhibited TX A2 biosynthesis (ID50 = 3.31 X 10(-3) M +/- 4.8 X 10(-7) M): this inhibiting act...
The effect of prostaglandin E1 on motility of the equine gut. Prostaglandin E1 was infused intravenously (25, 50 and 75 ng/kg/min) in three ponies. Changes in gastrointestinal mechanical and electrical activity were recorded from chronically implanted strain-gauge force transducers and electrodes. Dose-dependent responses were obtained: there were significant decreases in electrical spiking activity in the stomach, left large colon and small colon, with a corresponding decrease of activity in the left dorsal colon mechanogram. The small intestine was also affected, showing a decrease in both contraction rate and amplitude, which was more marked in the pr...
Failure of superoxide dismutase to alter equine arachidonic acid-induced platelet aggregation, in vitro or ex vivo. Superoxide dismutase (SOD), a free radical scavenger with anti-inflammatory activity, was administered IM to horses. Ex vivo platelet aggregation in response to arachidonic acid was monitored to determine whether exogenous SOD altered equine platelet prostaglandin metabolism. Preparations of platelet-rich plasma obtained before SOD administration were incubated with different concentrations of SOD and were aggregated with arachidonic acid. Superoxide dismutase did not exert a demonstrable effect, either ex vivo or in vitro. Aspirin abolished arachidonic acid-induced platelet aggregation in vit...
Effect of repeated flushing and a prostaglandin analogue on the estrous cycle of pony mares. An experiment was conducted to test the effect of repeated transcervical (non-surgical) uterine flushing and a prostaglandin analogue (PG) on the estrous cycle of pony mares. Uteri in group A were trancervically flushed for embryos 7 to 9 days post ovulation. In addition, group B mares were given 5 ml of PG by intramuscular injection on the day of flushing. Group C served as controls and were not flushed or given PG but were allowed to cycle normally. All mares (except controls) were bred A.I. every other day during estrus. There was no effect on embryo recovery rate from repeated flushing or ...
Induction of oestrus and ovulation by means of prostaglandin and gonadoliberin (GnRH) treatment in an old mare barren for two breeding seasons. A 17-year-old Nooitgedacht mare was presented in mid-summer after failing to conceive during the previous 2 breeding seasons. The mare conceived to service during a PG-induced oestrus when synthetic GnRH was used to induce ovulation.
Effects of repeated endotoxin injections on prostanoids, hemodynamics, endothelial cells, and survival in ponies. The objectives of this study were to determine the pathophysiological effects of increasing amounts of endotoxin administered intraperitoneally (IP) for 24 hr at which time an intravenous (IV) injection of endotoxin was given. The ability of flunixin meglumine (FM), a nonsteroidal antiinflammatory drug with antiprostaglandin activity, to provide protective effects was also determined. Eight ponies were divided into two groups of four ponies each; one group (untreated) received endotoxin only and the other group (treated) received endotoxin while being treated with flunixin. Hemodynamic and ser...
Endotoxin-induced eicosanoid production by equine vascular endothelial cells and neutrophils. Dispersed equine vascular endothelial cells grown in tissue culture, and freshly isolated neutrophils were used to determine direct effects of endotoxin on cyclooxygenase and lipoxygenase products. Endothelial cells (10(7)/ml) or neutrophils (2 X 10(6)/ml) were incubated with (a) buffer, (b) endotoxin (10 micrograms/ml), (c) endotoxin + flunixin meglumine (10 micrograms/ml), or (d) calcium ionophore, A23187 (10 micrograms/ml). Thromboxane (TxB2), prostacyclin (6-keto-PGF1 alpha), and leukotriene C4 (LTC4) were determined in the incubation fluid by radioimmunoassay. Thromboxane and prostacyclin...
Flunixin inhibits prostaglandin E2 production in equine inflammation. A model of acute inflammation was used in a cross-over study in Welsh mountain ponies to assess the actions of flunixin meglumine on selected components of a localised inflammatory reaction induced by injecting 0.5 ml of a 2 per cent carrageenin solution into subcutaneously implanted tissue cages. Samples of exudate were harvested at predetermined times between three and 48 hours. Increases in leucocyte numbers and protein concentration were not prevented by flunixin treatment. Prostaglandin E2-like activity was present in exudates from untreated ponies with the highest mean concentration occu...
Concentrations of 15-keto-13, 14-dihydro-prostaglandin F2 alpha in the mare during spontaneous and oxytocin induced foaling. Changes in plasma 15-keto-13, 14-dihydro-prostaglandin F2 alpha were monitored at frequent intervals before, during and after spontaneous deliveries (three mares) and foalings induced by oxytocin (eight mares). No evidence of increased concentrations of the prostaglandin metabolite was observed in the final 10 days of gestation. In spontaneously delivering mares, there was a marked increase from 3 ng/ml at -125 mins to 18 ng/ml at -65 mins to the highest observed value of 182 ng/ml at 20 mins pre-partum. Following delivery, concentrations declined rapidly to around 0.2 ng/ml. Further release o...