Function of prostaglandins, thromboxane A2, and histamine in hypersensitivity reaction to experimental bluetongue disease in calves

Calves given 2 subcutaneous inoculations (4 ml, 4.5 weeks apart) of an inactivated bluetongue virus serotype 17 (BTV-17), aluminum hydroxide adjuvant, and cimetidine (600 mg) or levamisole (819 mg, 6 ml) combination were challenge exposed with virulent BTV-17 (2.5 x 10(5) embryo lethal dose) 9 weeks after the 1st inoculation and were monitored for 35 days. Plasma prostaglandins (PG) and thromboxane (Tx) B2 were measured by radioimmunoassay. Histamine was assayed spectrofluorometrically. During the inoculation period (9 weeks from the 1st inoculation to challenge exposure) PGE and histamine increased from base-line concentrations of 34 +/- 3 pg/ml and 1.2 +/- 0.1 ng/ml to 83 +/- 8 pg/ml and 2.0 +/- 0.1 ng/ml, respectively, whereas PGF2 alpha decreased from base-line values of 356 +/- 41 pg/ml to 226 +/- 16 pg/ml. Significant (P less than or equal to 0.05) changes from base-line TxB2 values (110 +/- 7 pg/ml) were not observed during the inoculation period. After challenge exposure, maximum increases were observed in TxB2 (157 +/- 10 pg/ml), PGF2 alpha (713 +/- 93 pg/ml), PGE (140 +/- 30 pg/ml), and histamine (3.6 +/- 0.2 ng/ml) concentrations at 4, 7, 7, and 14 days after challenge exposure, respectively. Concentrations of PGF2 alpha and TxB2 decreased from base-line values to 211 +/- 42 pg/ml and 75 +/- 11 pg/ml, respectively, 21 days after challenge exposure and then returned to base-line values. Significant changes were not observed in plasma concentrations of 6-keto-PGF1 alpha. Results indicate that PG, TxA2, and histamine may be involved in the hypersensitivity reaction to BTV in cattle.     

Endotoxin-induced bovine mastitis: arachidonic acid metabolites in milk and plasma and effect of flunixin meglumine

Arachidonic acid metabolites (AAM) were measured in milk and plasma during the course of acute endotoxin-induced mastitis in 12 lactating cows. Mastitis was induced by intramammary challenge exposure with 10 micrograms of Escherichia coli (026:B6) endotoxin. Endotoxin was injected into the teat cistern via the teat canal of a single randomly selected rear quarter of each cow. Concentrations of prostaglandin (PG) F2 alpha and thromboxane (Tx) B2 in fat-free unextracted milk and of 15-keto-13,14-dihydro-PGF2 alpha in plasma were measured by radioimmunoassay. Total production of AAM in milk was determined by measuring quarter milk production. The AAM were compared in 6 cows administered flunixin meglumine (1.1 mg/kg of body weight) and in 6 cows administered saline solution. Concentrations of TxB2 in milk were significantly (P less than 0.001) increased during the early course of acute mastitis in endotoxin-treated quarters of cows not administered flunixin meglumine. Peak concentrations of TxB2 in milk occurred at 8 hours after endotoxin inoculation. Flunixin meglumine treatment produced significant (P less than 0.05) reductions in milk TxB2 and plasma 15-keto-13,14-dihydro-PGF2 alpha concentrations. Concentrations of PGF2 alpha in milk and total PGF2 alpha and TxB2 production per quarter per milking were not significantly influenced by endotoxin challenge or by flunixin meglumine treatment.     

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) prevented most of the endotoxin-induced changes and correlated with a significant decrease in plasma TxB2 and 6-keto PGF1 alpha concentrations, compared with concentrations in nontreated horses (ie, pretreated with saline solution). Pretreatment with phenylbutazone (2 mg/kg) attenuated the effects of endotoxin and was associated with a brief, early, significant increase in plasma TxB2 concentrations, but not in plasma 6-keto PGF1 alpha concentrations. Pretreatment with the thromboxane synthetase inhibitor did not appear to clinically benefit the horses involved; however, arachidonic acid metabolism was redirected to prostacyclin production.     

Prostaglandin and thromboxane concentrations in plasma and lung lavage fluids during sequential infection of vaccinated and nonvaccinated calves with bovine respiratory syncytial virus

The potential action of immunologic reactions and mediators released during the course of bovine respiratory syncytial virus infection in pathogenesis of the ensuing disease process was examined in an experimental infection study. Prostaglandin (PG) E2, PGF2 alpha 6-keto-PGF1 alpha, and thromboxane B2 (TxB2) concentrations were quantitated in plasma and lung lavage fluid by radioimmunoassay at 3- to 4-day intervals during a primary and secondary virus infection of vaccinated, nonvaccinated, and control (mock-infected) calves. A significant increase in the plasma PGE2 concentration for the nonvaccinated calves was noticed on day 3 after primary infection and on day 7 after secondary infection. The PGF2 alpha plasma concentrations increased significantly for the nonvaccinated groups on day 10 after primary infection. Plasma 6-keto-PGF1 alpha concentrations increased for nonvaccinated and vaccinated calves 3 days after the secondary infection. Plasma TxB2 concentrations during the primary exposure did not vary significantly. However, 14 days after the secondary exposure, both experimental groups had concentrations significantly greater than did the control group. Lung lavage fluid concentrations of TxB2 had peaks of activity 7 days after primary and secondary viral infections for the nonvaccinated group. Increases in plasma PG concentrations corresponded variably with disease expression, whereas plasma TxB2 concentrations did not have any correlation with disease expression. However, there was a significant correlation between TxB2 concentration in lung lavage fluid of the nonvaccinated group with disease expression 7 days after primary and secondary virus infection.(ABSTRACT TRUNCATED AT 250 WORDS)     

Role of eicosanoids, histamine, and serotonin in the pathogenesis of Klebsiella pneumoniae-induced bovine mastitis

By inoculating Klebsiella pneumoniae into the teat canals of mammary glands, coliform mastitis was induced experimentally in 6 lactating cows. Release of eicosanoids, histamine, and serotonin in plasma and milk was studied in response to 2 doses of K pneumoniae. A low dose (mean, 5,000 organisms/ml) was inoculated into cows 1 through 4, and a high dose (mean, 200,000 organisms/ml) was inoculated into cows 5 and 6. Milk and blood samples were collected before inoculation (0 hours), and hourly, from 3 to 24 hours after inoculation. Concentrations of prostaglandin F2 alpha (PGF2 alpha), prostaglandin E (PGE), thromboxane B2 (TxB2), histamine, and serotonin were measured in plasma and milk obtained from control (NaCl solution-inoculated) and infected quarters. Fluorometric analysis of milk from infected quarters revealed significantly increased histamine and serotonin concentrations regardless of the dose of K pneumoniae. The mean (+/- SEM) peak concentrations of histamine were significantly (P less than 0.01) increased from the preinoculation value of 44 (+/- 12) ng/ml to 312 (+/- 104) ng/ml in milk from infected quarters and 72 (+/- 24) ng/ml in milk from control quarters. The mean peak concentration of serotonin increased significantly from the preinoculation concentration of 436 (+/- 37) ng/ml to 1,754 (+/- 662) ng/ml and 4,867 (+/- 1,248) ng/ml in milk from control (P less than 0.02) and infected (P less than 0.001) quarters, respectively. However, serotonin concentration in milk from infected quarters was approximately 2.8 times greater than that in milk from control quarters. Concentrations of PGF2 alpha, PGE, and TxB2 in milk and plasma were evaluated by radioimmunoassay.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects on plasma endotoxin and eicosanoid concentrations and serum cytokine activities in horses competing in a 48-, 83-, or 159-km endurance ride under similar terrain and weather conditions

OBJECTIVE: To determine plasma endotoxin concentration in horses competing in a 48-, 83-, or 159-km endurance race and its importance with regard to physical, hematologic, or serum and plasma biochemical variables. ANIMAL: 3 horses. PROCEDURE: Weight and rectal temperature measurements and blood samples were obtained before, during, and after exercise. Blood samples were analyzed for plasma endotoxin concentration; serum antiendotoxin antibody titers; thromboxane B2 (TxB2) and 6-keto-prostaglandin F1alpha (PGF1alpha) concentrations; tumor necrosis factor alpha (TNFalpha) and interleukin-6 (IL-6) activities; WBC, plasma protein, lactate, serum electrolyte, and calcium concentrations; PCV; and creatine kinase activity. RESULTS: Detection of plasma endotoxin increased during exercise for horses competing at all distances but occurred more frequently in the 48- and 83-km groups. Plasma lactate concentration was significantly greater when endotoxin was concurrently detected. Endotoxin in plasma was not significantly associated with success of race completion. Plasma TxB2 and PGF1alpha concentrations and serum IL-6 activity significantly increased with exercise. Horses that had an excellent fitness level (as perceived by their owners) had greater decreases in serum antiendotoxin antibody titers during exercise than did horses perceived as less fit. In horses with better finish times, TxB2 and PGF1alpha concentrations were significantly greater and TNFalpha activity was significantly less than that of slower horses. CONCLUSIONS AND CLINICAL RELEVANCE: Endotoxemia developed during endurance racing, but was significantly correlated with increased plasma lactate concentration and not with other variables indicative of endotoxemia. Plasma TxB2 and PGF1alpha concentrations and serum TNFalpha activity may be associated with performance success.     

Role of prostaglandins in pathogenesis of bovine mastitis induced by Escherichia coli endotoxin

Four doses (5 to 100 micrograms, 1 dose/quarter) of Escherichia coli endotoxin were introduced into lactating mammary glands of 2 cows. There was no effect on milk prostaglandin (PG) E2 concentration, except that the concentration was increased from 200 pg/ml of milk to 1,060 pg/ml at post-treatment hour (PTH) 8 in cow 1 and from 75 to 420 pg/ml at PTH 4 in cow 2 after the highest dose 100 micrograms. Endotoxin caused a dose-dependent increase in milk PGF2 alpha concentrations in both cows. After the highest dose, PGF2 alpha was maximally increased from 200 to 3,500 pg/ml at PTH 4 in cow 1 and from 250 to 2,000 pg/ml in cow 2 at PTH 8. The instillation of 50 micrograms of endotoxin in all 8 quarters of 2 more lactating cows caused no significant (P greater than 0.05) changes in milk PGE2 and thromboxane B2 concentrations, whereas milk PGF2 alpha was significantly increased from the base-line value of 642 to 2,683, 1,189, and 2,281 pg/ml at PTH 4, 8, and 12, respectively. The 6-keto-PGF1 alpha was also significantly increased from the base-line value of 305 to 871, 631, and 600 pg/ml at the corresponding times, respectively. A marked increase in vascular permeability, as judged by high concentrations of serum albumin in the whey, was observed as early as PTH 4 and peaked at PTH 12 followed by a gradual decline, although it remained significantly increased over the control for 48 hours after treatment.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of administration of a phospholipid emulsion on the initial response of horses administered endotoxin

OBJECTIVE: To evaluate the effect of a phospholipid emulsion (PLE) on the initial response of horses to administration of endotoxin. ANIMALS: 12 healthy adult horses. PROCEDURES: Horses were assigned to 2 treatment groups (6 horses/group). The control group was administered 1 L of saline (0.9% NaCl) solution, and the treated group was administered PLE (200 mg/kg, IV); treatments were administered during a period of 120 minutes. An infusion of endotoxin was initiated in both groups starting 1 hour after initiation of the saline or PLE solutions. Physical examination and hemodynamic variables were recorded, and blood samples were analyzed for concentrations of tumor necrosis factor (TNF)-alpha, interleukin-6, thromboxane B2 (TxB2), 6 keto-prostaglandin F (PGF)1alpha, total leukocyte count, and PLE concentrations. An ANOVA was used to detect significant differences. RESULTS: Administration of PLE resulted in significantly lower rectal temperature, heart rate, cardiac output, right atrial pressure, and pulmonary artery pressure and higher total leukocyte counts in treated horses, compared with values for control horses. The TNF-alpha concentration was significantly less in treated horses than in control horses. The TxB2 and 6 keto-PGFF1alpha concentrations were significantly different between treated and control horses at 30 minutes (TxB2) and at 30 and 60 minutes (6 keto-PGF1alpha). CONCLUSIONS AND CLINICAL RELEVANCE: Prior infusion of PLE in horses administered a low dose of endotoxin decreased rectal temperature, heart rate, pulmonary artery pressure, and TNF-alpha concentrations. Results of this study support further evaluation of PLE for use in the treatment of horses with endotoxemia.     

Proadifen-induced production of prostacyclin by equine peritoneal macrophages

A study was performed to determine the effect of proadifen hydrochloride on prostacyclin (prostaglandin I2 [PGI2]) and thromboxane A2 (TxA2) synthesis by equine peritoneal macrophages and the effect of proadifen on endotoxin-induced synthesis of PGI2 and TxA2 by equine macrophages. Peritoneal macrophages (2.5 x 10(6)/ml) were incubated for 6 hours in tissue culture media containing 1) nothing (nontreated control), 2) proadifen hydrochloride (20, 100, 250, and 500 mumol/L, 3) endotoxin (5 ng/ml), or 4) the calcium ionophore A23187 (0.95 mumol/L). In a second series of experiments, peritoneal macrophages were incubated with endotoxin (5 ng/ml) and proadifen (250 umol/L), for 6 hours. Concentrations of 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) and thromboxane B2, the stable metabolites of PGI2 and TxA2, were determined in the incubation media by radioimmunoassay. Proadifen caused increased synthesis of PGI2 by equine macrophages, without affecting TxA2 production. The increased PGI2 production was similar to that induced by endotoxin and calcium ionophore; however, the latter 2 agents significantly stimulated TxA2 production as well (P less than 0.05). There were no significant differences among mean concentrations of 6-keto-PGF1 alpha in media from macrophages treated with 100, 250, or 500 mumol/L proadifen, but there was a significant curvilinear regression between their concentrations. The ratio of thromboxane B2 to 6-keto-PGF1 alpha was significantly lower than baseline in incubation media from macrophages exposed to proadifen, endotoxin, and calcium ionophore. Proadifen hydrochloride did not significantly change equine peritoneal macrophage production of PGI2 or TxA2 in response to endotoxin.     

Hemodynamics, plasma eicosanoid concentrations, and plasma biochemical changes in calves given multiple injections of Escherichia coli endotoxin

Twelve male neonatal calves (39 to 50 kg) were allotted to 3 groups of 4 calves each. All calves were anesthetized with halothane, and then Escherichia coli endotoxin was given intravenously (3 times) and intraperitoneally (3 times) during a 6-hour period. Group-1 calves were untreated, group-2 calves were pretreated with a low dose of flunixin meglumine (1.1 mg/kg of body weight), and group-3 calves were pretreated with a high dose of flunixin meglumine (4.4 mg/kg). In calves of group 1, the mean systemic arterial blood pressure (MABP) and cardiac output (CO) decreased, but pulmonary arterial pressure increased after the initial intravenous and intraperitoneal injections of endotoxin. In calves of this group, these changes were accompanied by increased plasma thromboxane B2 (TxB2) concentration. During this period, increased plasma TxB2 concentration or hemodynamic changes were not detected in calves of groups 2 and 3. Only calves of group 1 had altered hemodynamics early in the experiment; however, after 6 hours, calves of all 3 groups had similarly decreased CO and MABP. In calves of the untreated group, plasma 6-keto-prostaglandin (PG)F1 alpha concentration increased steadily from the beginning of the experiment until 3 hours later. The CO and MABP were low at the time when serum 6-keto-PGF1 alpha concentration was high; however, these 2 measurements also were low in treated calves who did not have correspondingly high plasma 6-keto-PGF1 alpha concentration. Regional blood flow analysis did not reveal correlations between prostanoid concentrations and altered blood flow to selected tissues.(ABSTRACT TRUNCATED AT 250 WORDS)     

A cooperative action of endothelin-1 with prostaglandin F(2alpha) on luteal function in the cow

Prostaglandin F(2alpha) (PGF(2alpha)) is the primary luteolysin in the cow, and luteal endothelin-1 (ET-1) interacts with PGF(2alpha) during the process of luteolysis. In contrast, a developing corpus luteum (CL) is refractory to exogenous administration of PGF(2alpha). Thus, the present study was aimed to investigate the functional relationship between ET-1 and PGF(2alpha) in the mid-CL (PGF(2alpha)-sensitive) and early-CL (PGF(2alpha)-refractory). In the mid-CL model, cows (n = 6/treatment) were assigned to receive one of five types of treatments on day 10 of the estrous cycle: (1) an injection of saline; control, (2) a 500 microg of PGF(2alpha) analogue (sufficient dose to induce luteolytis); full-PG, (3) an intraluteal injection of 0.25 mg ET-1; ET-1, (4) a 125 micro g of PGF(2alpha) (insufficient dose to induce luteolytis); 1/4PG or (5) an intraluteal injection of 0.25 mg ET-1 after administration of a insufficient dose of PGF(2alpha) analogue; 1/4PG/ET. In the early-CL model, cows were assigned to receive one of two types of treatments on day 5 of the estrous cycle: (1) a sufficient dose of PGF(2alpha) analogue; PG (n = 5) or (2) an intraluteal injection ET-1 after a sufficient dose of PGF(2alpha); PG/ET (n = 7). In the mid-CL model, 1/4PG/ET resulted in a rapid reduction of progesterone (P) concentrations similar to that in full-PG from the next day. However, the levels of P in 1/4PG/ET (1.5-2.5 ng/ml) kept significantly higher than that in full-PG (< 0.5 ng/ml). ET-1 or 1/4PG did not decrease plasma P concentrations (4-6 ng/ml). The plasma ET-1 levels increased with the full-PG administration. In the early-CL model, both treatments had no effect on plasma P increase and ET-1 levels. The overall results indicate that the intraluteal ET-1 injection after administration of insufficient dose of PGF(2alpha) induces the depression of P secretion in vivo during the mid luteal phase in the cow, supporting the concept that ET-1 is one of a local mediator of functional luteolysis in the cow. The result further indicates that the early-CL is not only PG-refractory but also ET-1-refractory.     

Effect of ACTH and CRH on plasma levels of cortisol and prostaglandin F2alpha metabolite in cycling gilts and castrated boars

The present study was designed to evaluate the effects of synthetic ACTH (1-24, tetracosactid) and porcine CRH on the plasma levels of cortisol and PGF2alpha metabolite in cycling gilts (n = 3) and castrated boars (n = 3). The experiments were designed as crossover studies for each gender separately. Each animal received, during three consecutive days; 1) ACTH (Synacthen Depot) at a dose of 10 microg/kg body weight in 5 ml physiological saline, 2) porcine CRH at a dose 0.6 microg/kg body weight in 5 ml physiological saline or 3) physiological saline (5 ml). The test substances were administered via an indwelling jugular cannula in randomized order according to a Latin square. The administration of ACTH to cycling gilts resulted in concomitant elevations of cortisol and PGF2alpha metabolite with peak levels reached at 70.0 +/- 10.0 and 33.3 +/- 6.7 min, respectively. Similarly, the administration of ACTH to castrated boars resulted in concomitant elevation of cortisol and PGF2alpha metabolite with peak levels reached at 60.0 +/- 0.0 and 20.0 +/- 0.0 min, respectively. Cortisol peaked at 20 min after administration of CRH in both cycling gilts and castrated boars with maximum levels of 149.3 +/- 16.5 nmol/l and 138.3 +/- 10.1 nmol/l, respectively. It can be concluded that administration of synthetic ACTH (tetracosactid) to pigs caused a concomitant elevation of cortisol and PGF2alpha metabolite levels in both cycling gilts as well as castrated boars. The administration of CRH to pigs resulted in an elevation of cortisol levels in both cycling gilts and castrated boars. Conversely, PGF2alpha metabolite levels were not influenced by the administration of CRH either in cycling gilts or in castrated boars.     

The influence of flunixin on the response to Salmonella typhimurium endotoxin in calves

The effects of intravenous injection of 0.5 microgram/kg body weight of Salmonella typhimurium endotoxin were studied in calves. The injection was followed by ruminal stasis and general dullness. The clinical signs disappeared within 24 hours. The injection was followed by a tremendous increase in the plasma level of 15-ketodihydro-PGF2 alpha, the main metabolite of PGF2 alpha. The injection was also associated with a profound leukopenia and significant decreases in the serum levels of iron, zinc and calcium. In order to study the role of prostaglandin (PG) for the development of endotoxin-induced changes a group of calves was pretreated with flunixin, a potent cyclo-oxygenase inhibitor, at a dose of 2.2 mg/kg body weight. Flunixin inhibited the PG release completely, but did not influence the other responses to endotoxin. The pyrogenic response to endotoxin was very moderate and it was suggested that fever is not the most suitable parameter for monitoring endotoxin effects in calves. The studied blood parameters (15-ketodihydro-PGF2 alpha, iron, zinc, calcium and the number of leukocytes) appeared to be much more sensitive.     

Endogenous prostaglandin F2 alpha release induced by physiologic saline solution infusion in utero in the mare: effect of temperature, osmolarity, and pH

Thirty mares with normal estrous cycles were allotted equally to 5 groups and infused with 250 ml of saline (NaCl) solution in utero on the seventh day after ovulation to test the effects of temperature, osmolarity, or pH of the saline solution on prostaglandin F2 alpha (PGF2 alpha) release and luteolysis. Intrauterine infusion of phosphate-buffered saline solution failed to alter the duration of the luteal phase, compared with the control group. Similarly, increasing the temperature of phosphate-buffered saline solution to 42 C or increasing (600 mosm) or decreasing osmolarity (less than 10 mosm) did not change the duration of the luteal phase. Decreasing the pH of saline solution to 3 caused significant (P less than 0.0001) releases of PGF2 alpha from the uterus within the first hour after infusion, and the luteal phase was shortened to 8.8 +/- 1.0 days (mean +/- SEM; control, 15 +/- 1.2 days). The results of this study showed that pH is the main factor in eliciting PGF2 alpha release by intrauterine infusion of a saline solution, whereas increased temperature and osmolarity have no effect on the release of PGF2 alpha. The intrauterine infusion of sterile water or physiologic saline (NaCl) solution has been used to induce estrus in mares for the past 50 years. Many investigators have reported that intrauterine infusion of physiologic saline solution or water at body temperature (37 C) or warmer up to 45 C) causes most "anestrous" mares to return to estrus in 1 to 8 days.(ABSTRACT TRUNCATED AT 250 WORDS)     

Serum concentrations of IGF-I in postpartum beef cows

Four experiments assessed changes in serum IGF-I under various physiologic conditions in postpartum cows. In Exp. 1, anestrous suckled cows (n = 25) were infused for 6 d with either saline or glucose at two different infusion rates. In Exp. 2, anestrous cows (n = 29) received either a saline (weaned and suckled controls) or 3 g/d phlorizin (weaned phlorizin) infusion for 3 d. Calves from the weaned groups were removed from 15 h before and throughout infusions. In Exp. 3, cycling suckled cows (n = 20) received prostaglandin F2 alpha (PGF2 alpha) when the 5-d saline or phlorizin infusion began. In Exp. 4, suckled cows (n = 20) had ad libitum access to feed or received 50% of control feed consumption from 30 to 40 d postpartum. Increasing glucose availability (Exp. 1) increased (P less than .05) serum IGF-I by 30 to 35%. IGF-I remained stable after weaning (Exp. 2) in phlorizin-infused cows (128.8 +/- 12.7 ng/ml), but increased (P less than .05) by 3 d after calf removal in weaned control cows (152.2 +/- 7.5 ng/ml). IGF-I also remained stable in phlorizin-infused cows following PGF2 alpha injection (Exp. 3), but increased in control cows by 2 d after PGF2 alpha (156.8 +/- 18.3 on d 2 vs. 133.7 +/- 9.8 ng/ml pre-injection; P less than .05) and remained elevated (P less than .05) during the periovulatory period. In cows receiving restricted feed intake (Exp. 4), IGF-I decreased by approximately 50% within 4 d of feed restriction (71.3 +/- 9.4 vs 137.4 +/- 16.6 ng/ml; P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Ovarian 3'5'-cyclic adenosine monophosphate and prostaglandins: a sequential comparison of gonadotropin-stimulated events in small and large ovine follicles

Luteinizing hormone (LH) stimulates a cascade of ovarian hormonal events that culminate in ovulation. This study was designed to investigate, in sheep, sequential changes in prostaglandin (PG) E2, PGF2 alpha, 6-keto-PGF1 alpha, and cyclic adenosine monophosphate (cAMP) in the theca, granulosa and follicular fluid of large preovulatory follicles and small nonovulatory follicles in response to LH. On d 15 postestrus, preovulatory or nonovulatory follicles were injected intrafollicularly with saline or LH. Ewes were then ovariectomized at 0, 2, 4, or 8 h postinjection. Injected follicles were excised; theca, granulosa and fluid were separated, weighed and assayed for cAMP and PG. Contents of cAMP in the theca, granulosa and fluid of preovulatory follicles increased (P less than .01) 2 to 4 h after injection of LH. Increases (P less than .05) in contents of PGE2 and PGF2 alpha in the theca and fluid of preovulatory follicles were observed between 4 and 8 h after injection of LH. The time courses of LH-induced synthesis of PGE2 and PGF2 alpha in preovulatory follicles were parallel. Luteinizing hormone had no effect on PGE2, PGF2 alpha or cAMP in any compartment of small follicles. Contents of 6-keto-PGF1 alpha varied with time in both theca and granulosa of large and small, saline- and LH-injected follicles. Although specific increases in cAMP and PG followed an injection of LH only in large follicles, the parallel temporal relationship of PGE2 and PGF2 alpha did not explain the dichotomous functions ascribed to PGE2 and PGF2 alpha during the periovulatory period.     

Effect of hypertonic vs isotonic saline solution on responses to sublethal Escherichia coli endotoxemia in horses

Cardiovascular responses to sublethal endotoxin infusion (Escherichia coli, 50 micrograms/ml in lactated Ringer solution at 100 ml/h until pulmonary arterial pressure increased by 10 mm of Hg) were measured 2 times in 5 standing horses. In a 2-period crossover experimental design, horses were either administered hypertonic (2,400 mosm/kg of body weight, IV) or isotonic (300 mosm/kg, IV) NaCl solution after endotoxin challenges. Each solution was administered at a dose of 5 ml/kg (infusion rate, 80 ml/min). Complete data sets (mean arterial, central venous, and pulmonary arterial pressures, pulmonary arterial blood temperature, cardiac output, total peripheral vascular resistance, heart rate, plasma osmolality, plasma concentration of Na, K, Cl, and total protein, blood lactate concentration, and PCV) were collected at 0 (baseline, before endotoxin infusion), 0.25, 1, 1.5, 2, 2.5, 3, 3.5, 4, and 4.5 hours after initiation of the endotoxin infusion. Blood constituents alone were measured at 0.5 hour and cardiovascular variables alone were evaluated at 0.75 hour. By 0.25 hour, endotoxin infusion was completed, a data set was collected, and saline infusion was initiated. By 0.75 hour, saline solutions had been completely administered. Mean (+/- SEM) cardiac output decreased (99.76 +/- 3.66 to 72.7 +/- 2.35 ml/min/kg) and total peripheral resistance (1.0 +/- 0.047 to 1.37 +/- 0.049 mm of Hg/ml/min/kg) and pulmonary arterial pressure (33.4 +/- 0.86 to 58.3 +/- 1.18 mm of Hg) increased for both trials by 0.25 hour after initiation of the endotoxin infusion and prior to fluid administration. For the remainder of the protocol, cardiac output was increased and total peripheral resistance was decreased during the hypertonic, compared with the isotonic, saline trial.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of flunixin meglumine on endotoxin-induced prostaglandin F2 alpha secretion during early pregnancy in mares

The role of prostaglandin F2 alpha (PGF2 alpha) in embryonic loss following induced endotoxemia was studied in mares that were 21 to 44 days pregnant. Thirteen pregnant mares were treated with a nonsteroidal anti-inflammatory drug, flunixin meglumine, to inhibit the synthesis of PGF2 alpha caused by Salmonella typhimurium endotoxin given IV. Flunixin meglumine was administered either before injection of the endotoxin (group 1, -10 min; n = 7), or after endotoxin injection into the mares (group 2, 1 hour, n = 3; group 3, 2 hours, n = 3); 12 pregnant mares (group 4) were given only S typhimurium endotoxin. In group 4, the secretion of PGF2 alpha, as determined by plasma 15-keto-13,14-dihydro-PGF2 alpha concentrations, was biphasic, initially peaking at 30 minutes followed by a second, larger peak approximately 105 minutes after the endotoxin was given IV. When flunixin meglumine was administered at -10 minutes, synthesis of PGF2 alpha was inhibited for several hours, after administration of flunixin meglumine at 1 hour, the second secretory surge of PGF2 alpha was blocked, and administration of the drug at 2 hours did not substantially modify the secretion of PGF2 alpha. Plasma progesterone concentrations were unchanged after endotoxin injections were given in group 1. In group 2, progesterone values decreased less than 2 ng/ml and remained low for several days. In group 3 and group 4, progesterone concentrations decreased to values less than 0.5 ng/ml by 48 hours after endotoxin injections were given.(ABSTRACT TRUNCATED AT 250 WORDS)     

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 decreased serum TxB2 generation while significantly increasing serum 6-keto PGF1 alpha levels, thus confirming its selectivity as a thromboxane synthetase inhibitor.     

Endocrine,metabolic and clinical effects of intravenous endotoxin injection after pre-treatment with meloxicam in heifers

Meloxicam (M), a non-steroid anti-inflammatory drug for use in animals, reduces prostaglandin (PG) synthesis by inhibiting cyclooxygenases-1 and -2. The aim of this study was to evaluate M's capability to prevent the inflammatory response elicited by endotoxin (ET). Furthermore, we wanted to evaluate a possible effect of M on delta13-reductase and 15-hydroxy prostanoate dehydrogenase, enzymes responsible for the initial metabolism of PGF2alpha. Four heifers acting as their own controls were used in the study. The heifers received an i.v. injection of either saline (S) or M (0.5 mg/kg) at 1.5 h before an i.v. injection of ET (50 ng/kg b.w. i.v.). The trial lasted 57 h after ET injection and blood samples were withdrawn for analyses of 15-ketodihydro-PGF2alpha (PG metabolite), cortisol, white blood cells (WBC), Fe, Zn and Ca. Clinical examinations were performed throughout the trial. In the S + ET trial, ET injection elicited a rapid increase of the PG metabolite, a prolonged cortisol release and reduced levels of WBC, Fe, Zn and Ca. General appearance and body temperature were affected. In the M + ET trial the PG release was totally abolished, the cortisol release was reduced and the clinical effect was milder, also effects on Fe, Zn and Ca were milder in the M + ET trial, but M did not prevent the pyrogenic effect of ET. In the next two trials, we injected PGF2alpha (500 ng/kg i.v.) with and without M pre-treatment. After PGF2alpha injection, plasma samples were collected for measurement of the PG metabolite. M had no effect on PGF2alpha metabolism. In conclusion, M effectively suppresses several of the inflammatory reactions seen after ET injections and has no major influence on the PGF2alpha metabolism.