Hemostatic and Fibrinolytic Indices in Neonatal Foals with Presumed Septicemia

Thirteen coagulation tests evaluating hemostatic and fibrinolytic indices and serum cytokine and plasma endotoxin concentrations were obtained in 34 foals with a positive sepsis score (septic group) and 46 age-matched healthy foals. Compared to healthy foals, the prothrombin, activated partial thromboplastin, and whole blood recalcification times were significantly longer in septic foals. The fibrinogen and fibrin degradation products concentrations, percent plasminogen, alpha-2 antiplasmin, and plasminogen activator inhibitor activities, and tumor necrosis factor and interleukin-6 activities were greater in septic foals. Protein C antigen and antithrombin III activity were significantly lower in septic foals. Blood cultures were positive for growth and endotoxin was detected in 19 of 29 and 15 of 30 septic foals, respectively. In septicemic foals with detectable endotoxin in the plasma, the prothrombin and activated partial thromboplastin times were significantly longer and the plasminogen and antithrombin III activities were significantly less than in septic foals in which endotoxin was not detected. Twenty-three of the 34 septic foals did not survive. Septic foals that did not survive were most likely to have a positive blood culture in which a gram-negative organism was isolated. Histopathologic evidence of hemorrhage was evident in 11 foals at postmortem examination and thrombosis was identified in 2 foals. The prothrombin time was significantly longer in foals that had multisite hemorrhage at postmortem examination. The results of this study indicate that clinically relevant alternations in hemostatic and fibrinolytic indices occur in neonatal foals with septicemia and that derangements can be correlated with the presence of endotoxin in plasma. Derangements in hemostatic or fibrinolytic indices were helpful in identification of septic foals with increased risk of coagulopathy, but were not helpful in predicting hemorrhage as compared to thrombus formation. Survival of septicemic foals was correlated with gram-negative bacteremia, but not with the presence of endotoxin or coagulopathy.     

Peritoneal d-Dimer Concentration for Assessing Peritoneal Fibrinolytic Activity in Horses with Colic

Background: Plasma d -dimer concentration is a useful marker to assess systemic coagulation and fibrinolytic activities in humans, dogs, and horses. Peritoneal fibrinolytic activity increases in horses with colic, especially in horses with endotoxin in the peritoneal fluid.
Hypothesis/Objectives: Peritoneal d -dimer concentration can be used to assess peritoneal fibrinolytic activity in horses with severe gastrointestinal (GI) disorders and altered peritoneal fluid.
Animals: Two hundred and twenty-one colic horses and 15 control horses.
Methods: Prospective observational clinical study. Blood and peritoneal fluid were collected on admission. Horses were grouped according to diagnosis, peritoneal fluid analysis, and outcome. Peritoneal d -dimer concentration was determined, together with peritoneal tissue-plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI-1) activities. Plasma d -dimer concentration also was measured.
Results: Peritoneal d -dimer concentration was significantly higher in all colic groups compared with controls, and in horses with enteritis, peritonitis, and ischemic disorders compared with horses with large intestinal obstructions. Peritoneal d -dimer concentration was significantly higher in horses with altered peritoneal fluid (modified transudate and exudate) compared with horses with normal peritoneal fluid analysis. Plasma d -dimer concentration also was significantly higher in the peritonitis group, and in horses with altered peritoneal fluid analysis. Peritoneal and plasma d -dimer concentrations also were significantly higher in nonsurvivors. Peritoneal d -dimer concentration was significantly correlated with decreased peritoneal t-PA activity and increased peritoneal PAI-1 activity.
Conclusions and Clinical Importance: Peritoneal d -dimer concentration is markedly higher in severe GI disorders, and it can be used to assess peritoneal fibrinolytic activity in horses with colic.     

Preoperative and postoperative hemostatic profiles of dogs undergoing ovariohysterectomy.

Hemostatic profiles were evaluated in 15 healthy dogs immediately before and 24 hours after celiotomy for routine ovariohysterectomy. Prothrombin time, activated partial thromboplastin time, fibrinogen, fibrin degradation products, antithrombin III activity, platelet count, and hemogram were measured. There were no significant changes in prothrombin time, activated partial thromboplastin time, fibrin degradation products, antithrombin III activity, or platelet count. Fibrinogen concentration was significantly higher following surgery. Postoperative leukocyte differential counts were typical of stress leukograms, and were characterized by leukocytosis, neutrophilia, lymphopenia and eosinopenia. Mild decreases in packed cell volume, red blood cell count and hemoglobin concentration were consistent with minor blood loss during surgery or fluid retention and hemodilution postoperatively. It was concluded that celiotomy and routine ovariohysterectomy in healthy dogs did not alter hemostatic profiles 24 hours after surgery. Abnormal postoperative hemostatic profiles should not be attributed to surgery alone; other causes of abnormal hemostatic profiles should be investigated.     

Hemostatic response to surgical neutering via ovariectomy and ovariohysterectomy in dogs

Objective-To investigate the hemostatic response to surgery and compare the response for ovariohysterectomy with that for ovariectomy and to evaluate the usefulness of thromboelastography on plasma samples. Animals-42 female dogs. Procedures-Dogs were assigned to undergo ovariohysterectomy or ovariectomy. Blood samples were collected immediately before and 1, 6, and 24 hours after surgery and stored at -80°C for subsequent analysis. Plasma samples were subjected to thromboelastography after thawing. In addition, coagulation variables were measured, including concentrations of von Willebrand factor antigen, fibrinogen, antithrombin, and protein C; activity of factor VIII; activated partial thromboplastin time; prothrombin time; and thrombin time. The fibrinolytic response was assessed via concentrations of D-dimer, plasminogen, and α-2-antiplasmin (plasmin inhibitor). Results-Substantial hemostatic and fibrinolytic activation was evident after surgery in both groups, as characterized by significantly increased global clot strength and an overall hypercoagulable state at 4 hours after surgery in addition to decreases in von Willebrand factor antigen and factor VIII concentrations and shortened prothrombin and thrombin times. The dogs also typically had activation of the fibrinolytic system, as evidenced by increased postoperative concentrations of D-dimer, plasminogen, and plasmin inhibitor. Differences between the 2 groups could not be detected for any variables. Conclusions and Clinical Relevance-Elective surgery with limited tissue trauma induced hemostatic activation in dogs, which led to hypercoagulability after surgery. A difference between the ovariohysterectomy and ovariectomy groups was not detected. Thromboelastography can be used on plasma samples and may be useful for evaluating patterns over time.     

Fibrinolytic Responses of the Equine Peritoneum to Abdominal Surgery,Surgical Trauma,and Intraperitoneal Sodium Hyaluronate

Postoperative abdominal adhesions are known to present clinical challenges to the surgeon. Adhesion formation is a balance modulated by the fibrinolytic system. The key components involved are the tissue plasminogen activators (tPAs) and plasminogen activator inhibitors (PAI-1 and PAI-2). Sodium hyaluronate (HA) has been shown to reduce the incidence and severity of adhesions in horses. The objectives of this study were to measure tPA and PAI-1 activity in equine peritoneum and evaluate the effect of 0.4% HA solution on local tPA and PAI-1 activity. An exploratory laparotomy was performed and local serosal trauma was induced by using an established abrasion model. Our study involved two groups: in the first group (n = 6) 0.4% HA was used in all intestinal manipulations, whereas in the second group (n = 6) sterile saline was used. Parietal peritoneum, jejunal seromuscular biopsies at abraded sites (AJ) and nonabraded sites, and peritoneal fluid samples were taken at time 0- and at 30-minute intervals up to 120 minutes. Peritoneum tPA activity was significantly decreased at 60 and 90 minutes. Interestingly, AJ contained significantly higher tPA activity than nonabraded sites at 30-, 60-, 90-, and 120-minute intervals in control horses. The increase in tPA activity with AJ in treated (HA) horses was significantly attenuated as compared with the control (saline). Detectable levels of PAI-1 activity could not be identified in our samples. The results of our study indicate that exploratory celiotomy in horses is associated with a significant decrease in peritoneal tPA activity, and HA significantly decreases the fibrinolytic response of the jejunum to surgical trauma. Further characterization of these responses will hopefully lead to new pharmacologic strategies for adhesion prevention.     

Disseminated Intravascular Coagulation in Ponies with Surgically Induced Strangulation Obstruction of the Small Intestine

Total strangulation obstruction (S/O) of the jejuno-ileum was produced in a group of randomly selected ponies. Peripheral blood samples were collected prior to surgery and at 3-hour intervals following obstruction. A coagulation profile consisting of platelet count, fibrinogen titer (FT), prothrombin time (PT), activated partial thromboplastin time (APTT), and serial dilution protamine sulfate test (SDPS) for fibrin monomers (FM) and/or early fibrin degradation products (fdp) was evaluated. The packed cell volume (PCV) and total plasma protein (TPP) were also determined. Concurrent peritoneal fluid samples were assessed grossly. Sham-operated (sham) ponies were treated in a similar manner, excluding the production of a strangulation obstruction of the small intestine. Notable coagulopathies occurred in the S/O group. PT and APTT were increased significantly in samples collected within 6 hours of death. All S/O horses developed strongly positive SDPS reactions, while sham ponies, presurgical S/O ponies, and early S/O postsurgical samples were unremarkable. There were no significant shifts in the fibrinogen titer. Platelet counts were significantly decreased during the final 10% of sampling time in S/O horses. The coagulopathies observed in the S/O ponies appear to be secondary to the pathophysiologic changes produced by the S/O and not related to surgical trauma.     

Use of newly developed assays for protein C and plasminogen in horses with signs of colic

Protein C content and plasminogen activity were measured in plasma from 100 horses with signs of colic. Data were analyzed by grouping horses 4 ways. Each horse was allotted to 1 of 2 outcome groups (survivors and nonsurvivors), 1 of 3 broad-category diagnosis groups (inflammatory disorders, strangulating obstructions, and all other gastrointestinal disorders), and 1 of 2 clinical management groups (medical and surgical). In a fourth grouping, all horses (although numbers of horses included in each subgroup were small) were assigned either to specific diagnostic groups that had high expectation for activated hemostasis (intestinal ischemia, endotoxemia, jugular thrombosis, peritoneal adhesions, and laminitis) or to a control group, in which active hemostasis was unlikely. Within 2 to 24 hours after admission, nonsurvivors developed lower protein C content than did survivors. Protein C content and plasminogen activity became low during hospitalization in horses with strangulating obstructions and in horses having surgery. The results from the grouping by specific diagnosis must be considered pilot data because the numbers of horses in each subgroup were small. Although not statistically significant, trends were noticed in protein C and plasminogen: (1) horses with intestinal ischemia and endotoxemia developed low protein C content and plasminogen activity, (2) protein C content became low in horses that developed peritoneal adhesions or laminitis, and (3) plasminogen activity became low in horses that developed jugular thrombosis. Low protein C content or low plasminogen activity, or both, may be useful as predictors for outcome and for these specific complications of equine colic.(ABSTRACT TRUNCATED AT 250 WORDS)     

Fibrinolytic Activity in Plasma From Horses With Gastrointestinal Diseases: Changes Associated With Diagnosis, Surgery, and Outcome

Plasma fibrinolytic activity was evaluated over 5 consecutive days in 59 horses admitted to the Large Animal Teaching Hospital with acute gastrointestinal diseases. Only horses hospitalized for at least 5 days were included in the study. Tissue plasminogen activator (tPA) and plasminogen activator inhibitor type-1 (PAI-1) were quantitated using standard chromogenic activity assays. Statistical analyses were performed using analysis of variance; differences were considered significant when P < .05. Activity of PAI-1, the primary endogenous inhibitor of fibrinolysis, was significantly increased on hospital days 2, 4, and 5 in horses that died, when compared with those that were discharged from the hospital. Plasma PAI-1 activity was not different at admission, but was significantly increased on hospital days 2 and 3 in horses that underwent surgery, when compared with those that did not, suggesting an acute phase response to surgical intervention. Horses with strangulating intestinal lesions had significantly increased PAI-1 activity on day 3, while PAI-1 activity was significantly greater in horses with inflammatory conditions at the time of admission, when compared with horses with strangulating or nonstrangulating/noninflammatory lesions. Among all horses, PAI-1 activity was significantly higher and tPA activity was significantly lower on day 2 when compared with other hospital days. These results suggest that fibrinolysis is inhibited early in the course of inflammatory gastrointestinal diseases and in response to surgery. In addition, among all horses, the prognosis for survival was poor for those with persistently increased PAI-1 activity, reflecting treatment failure and the loss of hemostatic regulation.     

Clinicopathologic evidence of disseminated intravascular coagulation in horses with acute colitis

OBJECTIVE: To detect subclinical disseminated intravascular coagulation (DIC) in horses with colitis and to determine any association between the diagnosis of subclinical DIC and outcome or occurrence of complications in horses with colitis. DESIGN: Prospective study. ANIMALS: 37 horses admitted to a veterinary teaching hospital for treatment of acute colitis. PROCEDURE: Coagulation profiles were obtained on each horse 0, 24, and 48 hours after admission. Six tests were performed: platelet count, plasma fibrinogen concentration, prothrombin time, activated partial thromboplastin time, antithrombin activity, and serum fibrin degradation products concentration. RESULTS: A clinicopathologic diagnosis of subclinical DIC was made if 3 of the 6 tests had abnormal results at any 1 sample period. No horse had clinical signs of DIC at the time of sampling. Twelve of 37 (32%) horses met the criteria for diagnosis of subclinical DIC within a 1-year period. Outcome was defined as survival or nonsurvival. Five of 12 horses with subclinical DIC and 2 of 25 horses without subclinical DIC did not survive. Crude odds ratio analysis revealed a horse with acute colitis was 8 times as likely to die or be euthanatized if a diagnosis of subclinical DIC was made. CONCLUSIONS AND CLINICAL RELEVANCE: Clinicopathologic evidence of DIC is common and is significantly associated with a poor outcome in horses with acute colitis. Treatment of subclinical DIC may influence outcome in horses with acute colitis.     

Hemostatic abnormalities in equine colic

Hemostatic profiles were determined in 30 horses with clinical colic. Blood samples were obtained at the time of the animal's admission, and the following hemostatic tests were done: blood platelet count, plasma fibrinogen, plasma antithrombin, prothrombin time, partial thromboplastin time, thrombin time, protamine sulfate test for soluble fibrin monomer, and fibrin-fibrinogen degradation products. The patients were categorized in retrospect, according to the cause of the colic: group 1--colic associated with colitis and/or severe diarrhea, group 2--colic associated with torsion or obstruction of the intestine, and group 3--colic associated with impaction of the intestine or the presence of enteroliths. Of the 30 horses with colic, 28 had at least 1 abnormality in their coagulogram--the most frequent abnormalities being high plasma fibrinogen concentration, high circulating soluble fibrin monomer, or a long partial thromboplastin time or thrombin time. The horses in group 1 seemed to have the most severe coagulopathies, as indicated by the average number of demonstrable abnormalities. The horses in group 3 showed the fewest abnormalities--usually a high plasma concentrations of fibrinogen and/or soluble fibrin monomer. The results indicated that hemostatic abnormalities are not uncommon in horses with gastrointestinal disease and colic--the degree of severity depending to some extent on the cause of the colic.     

Effects of enterocentesis on peritoneal fluid constituents in the horse

Peritoneal fluid was collected from 15 clinically normal horses and was analyzed for nucleated cell (NC) counts and specific gravity. Six horses (controls, group 1) were subjected to abdominocentesis only, with a teat cannula, every 24 hours for 5 days. There were no marked changes in the peritoneal fluid of these horses over the 5-day period. Peritoneal fluid was collected from 6 other horses (group 2) with an 8.89-cm 18-gauge needle. The needle was then advanced until intestinal fluid was obtained. Peritoneal fluid was then collected with teat cannulas at 24-hour intervals for an additional 4 days. Peritoneal fluid NC counts from group 2 horses were significantly increased (P less than 0.05) at peak values 2 days after enterocentesis. Specific gravities of peritoneal fluid from group 2 horses were increased on days 1 and 2 after enterocentesis (P greater than 0.05). Peritoneal fluid from 3 other horses (group 3) was collected before enterocentesis (base line) and again at 4-hour intervals after enterocentesis. Peritoneal fluid NC counts of group 3 horses were markedly increased above base-line values 4 hours after enterocentesis and continued to increase for up to 12 hours after enterocentesis when the experiment was terminated. All horses that underwent enterocentesis remained clinically normal except 1 group 3 horse that had a fever (39.6 C) 24 hours after enterocentesis.     

实验性传染性法氏囊病凝血功能动态研究

９０只健康白来航雏鸡于５０日龄 种传染性法氏囊病理毒强化株。分别于攻毒前（即攻毒０ｈ），攻毒后２４ｈ，４８ｈ和７２ｈ随机抽承５只鸡，心脏采血，对其６项凝血指标进行动态测定。结果表明，攻毒后２４ｈ血浆再钙化时间和凝血酶原时间显著延长；４８ｈ不凝；７２ｈ逐渐恢复。     

Pharmacokinetics of fluconazole following intravenous and oral administration and body fluid concentrations of fluconazole following repeated oral dosing in horses

OBJECTIVE: To determine the pharmacokinetics of fluconazole in horses. ANIMALS: 6 clinically normal adult horses. PROCEDURE: Fluconazole (10 mg/kg of body weight) was administered intravenously or orally with 2 weeks between treatments. Plasma fluconazole concentrations were determined prior to and 10, 20, 30, 40, and 60 minutes and 2, 4, 6, 8, 10, 12, 24, 36, 48, 60, and 72 hours after administration. A long-term oral dosing regimen was designed in which all horses received a loading dose of fluconazole (14 mg/kg) followed by 5 mg/kg every 24 hours for 10 days. Fluconazole concentrations were determined in aqueous humor, plasma, CSF, synovial fluid, and urine after administration of the final dose. RESULTS: Mean (+/- SD) apparent volume of distribution of fluconazole at steady state was 1.21+/-0.01 L/kg. Systemic availability and time to maximum plasma concentration following oral administration were 101.24+/-27.50% and 1.97+/-1.68 hours, respectively. Maximum plasma concentrations and terminal half-lives after IV and oral administration were similar. Plasma, CSF, synovial fluid, aqueous humor, and urine concentrations of fluconazole after long-term oral administration of fluconazole were 30.50+/-23.88, 14.99+/-1.86, 14.19+/-5.07, 11.39+/-2.83, and 56.99+/-32.87 microg/ml, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Bioavailability of fluconazole was high after oral administration to horses. Long-term oral administration maintained plasma and body fluid concentrations of fluconazole above the mean inhibitory concentration (8.0 mg/ml) reported for fungal pathogens in horses. Fluconazole may be an appropriate agent for treatment of fungal infections in horses.     

Kinetics of Plasma Cell‐Free DNA and Creatine Kinase in a Canine Model of Tissue Injury

Background

Cell‐free DNA (cfDNA) comprises short, double‐stranded circulating DNA sequences released from damaged cells. In people, cfDNA concentrations correlate well with disease severity and tissue damage. No reports are available regarding cfDNA kinetics in dogs.

Objectives/Hypothesis

Cell‐free DNA will have a short biological half‐life and would be able to stratify mild, moderate, and severe tissue injury. Our study aims were to determine the kinetics and biological half‐life of cfDNA and to contrast them with those of creatine kinase (CK).

Animals

Three groups of 10 dogs undergoing open ovariohysterectomy, surgery for cranial cruciate ligament rupture (CCLR), or hemilaminectomy.

Methods

Plasma for cfDNA and CK analysis was collected at admission, at induction of anesthesia, postsurgery (time 0) and at 6, 12, 24, 36, 48, 60, and 72 hours after surgery.

Results

The biological half‐life of plasma cfDNA and CK were 5.64 hours (95% confidence interval [CI 95], 4.36–7.98 hours) and 28.7 hours (CI95, 25.3–33.3 hours), respectively. In the hemilaminectomy group, cfDNA concentrations differed significantly from admission at 6–12 hours after surgery. Creatine kinase activity differed among the surgical groups and reached a peak 6 hours after surgery. In the ovariohysterectomy and CCLR groups, plasma CK activity 72 hours after surgery did not differ from admission activity of the ovariohysterectomy group. In contrast, in the hemilaminectomy group, plasma CK activity after 72 hours did not return to the ovariohysterectomy group admission activity.

Conclusions and Clinical Importance

Plasma CK activity has a longer biological half‐life than previously thought. In contrast to plasma CK activity, cfDNA has a short half‐life and could be a useful marker for peracute severe tissue injury.     

Evaluation of cellular and biochemical parameters of blood and peritoneal fluid following exploratory laparotomy in the goat

To evaluate the effects of exploratory laparotomy on cellular and biochemical parameters of blood and peritoneal fluid, an experiment was conducted using 10 Iranian cross-bred male goats. Approximately 10 ml of blood and 1-1.5 ml of peritoneal fluid were collected from all animals prior to operation for estimation of control values. Exploratory laparotomy was performed under local analgesia. Blood and peritoneal fluid samples were collected at 24, 48, 72 and 96 h after exploratory laparotomy. The results revealed that after exploratory laparotomy, the number of white blood cells and the percentage and absolute number of neutrophils and band neutrophils significantly increased (P < 0.05). However, the percentage of lymphocytes decreased significantly (P < 0.05). The concentrations of blood urea nitrogen significantly increased (P < 0.05). Furthermore, following the operation, the percentage and absolute number of neutrophils in the peritoneal fluid significantly increased (P < 0.05). In contrast, the percentage of lymphocytes in the peritoneal fluid decreased significantly (P < 0.05). The concentration of protein in the peritoneal fluid increased significantly (P < 0.05).     

Bovine peritoneum: fibrinolytic activity and adhesion formation

The fibrinolytic activity of peritoneum was evaluated in 4-month-old calves before and after peritoneal trauma. In each calf, a peritoneal resection, abrasion, sutured incision, and nonsutured incision were performed. These 4 trauma sites were evaluated for fibrinolytic activity and adhesion formation at 1 of 6 posttrauma intervals (1, 2, 3, 5, 8, or 14 days). Peritoneal plasminogen activator and fibrinolytic inhibitor activities from pre- and posttrauma samples were evaluated, using a fibrin-slide incubation technique. Calf peritoneal specimens consistently had fibrinolytic inhibitor activity, but did not have plasminogen activator activity. Significant differences were not found between fibrinolytic activity before or after trauma and a significant correlation was not found between fibrinolytic activity and the presence of or severity of adhesions.     

Use of clinical pathology in evaluation of horses with colic

Clinical pathology is a valuable adjunct to physical examination of cases of colic. The present review considers evaluation of cases of colic for three main purposes: (1) making a prognosis, (2) deciding whether to operate, and (3) making a diagnosis. Blood tests noted to be useful for prognostication were hematocrit, lactate and urea nitrogen concentrations, pH, anion gap, fibrin/fibrinogen degradation products, antithrombin III activity, prothrombin time, and thrombin time. Horses with a poor prognosis often have relative polycythemia, marked lactic acidosis, high anion gap, azotemia, and coagulation abnormalities evidenced by increased fibrin/fibrinogen degradation products, decreased antithrombin III activity, and prolonged prothrombin and thrombin times. The decision to operate is usually a clinical one, supported by relative polycythemia, hyperglycemia, and, possibly, abnormal peritoneal fluid analysis. Diagnosis of the primary problem (causing the colicky signs) is also often based largely on physical examination. However, peritoneal fluid analysis provides worthwhile data, especially in cases of peritonitis or intestinal ischemia and infarction.     

Induction of the acute-phase cytokine, hepatocyte-stimulating factor/interleukin 6, in the circulation of horses treated with endotoxin.

Because hepatocyte-stimulating factor/interleukin 6 (IL-6) is the principal inducer of acute-phase protein synthesis in the liver, quantification of its activity in blood provides an early and sensitive assessment of the acute-phase response. Circulating IL-6 activity was monitored in 4 adult horses for 72 hours after IV administration of endotoxin. In 4 experiments performed at weekly intervals and in randomized order, each horse was given endotoxin--1,000 30, 1, and 0 ng/kg of body weight. Plasma IL-6 activity was quantified as the ability to promote growth of the IL-6-dependent B-cell hybridoma, B13.29 clone B9. Interleukin-6 activity (171 +/- 10.2 U/ml) was found in all pretreatment plasma samples and was significantly (P less than 0.05) increased above baseline from 2 to 12 hours after 1,000 ng of endotoxin/kg was given and at 3 hours after 30 ng of endotoxin/kg was given. After 1,000- or 30-ng/kgt dosage of endotoxin, peak plasma IL-6 activity (10,128 +/- 4,096 and 1,555 +/- 1,326 U/ml, respectively) was observed for 3 hours. The IL-6 response of endotoxin-treated horses began about 1 hour after tumor necrosis factor appeared in the circulation, and its course closely approximated the endotoxin-induced febrile reaction. Significant increase in plasma IL-6 activity was not detected in horses given 1 ng of endotoxin/kg or control buffer.     

The effects of phenylbutazone on the morphology and prostaglandin concentrations of the pyloric mucosa of the equine stomach

Phenylbutazone, a nonsteroidal anti-inflammatory drug known to produce gastric ulcers, was administered intravenously (13.46 mg/kg body weight) daily to 12 horses. Horses were euthanatized daily after 24, 48, 72, and 96 hours following the initial injection. Eight untreated horses served as controls. Small multifocal pyloric erosions were seen after 24 hours and then progressed in severity over time. The erosions were characterized by sloughing of the surface epithelium, subepithelial bleb formation, necrosis of the lamina propria, degeneration of the walls of subsurface capillaries, and microthrombosis of the capillaries of the pyloric mucosa. Large numbers of neutrophils with abundant fibrin and cellular debris were present at the erosion sites. Eroded pyloric mucosa and adjacent macroscopically intact mucosa were examined ultrastructurally. In both the macroscopically eroded mucosa and multifocally in the adjacent macroscopically uneroded mucosa, there was cellular swelling of the endothelium, pericytes, and smooth muscle cells of arterioles. In capillaries and post-capillary venules, the endothelium ranged from swollen to lysed and necrotic. Extensive extravasation of erythrocytes and edema were seen. These lesions were not seen in the control horses. Phenylbutazone produces a microvascular injury that is associated with the formation of pyloric erosions in horses. The pyloric mucosa of six horses was assayed for prostacyclin and prostaglandin E2 at 48 and 96 hours following the initial injection. There was no statistically significant difference between prostaglandin concentrations in the mucosa of control and treated horses. It was concluded that there was little correlation between pyloric mucosal prostaglandin concentrations and pyloric erosions after 48 hours.