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.     

The effect of topical tripeptide-copper complex on healing of ischemic open wounds

OBJECTIVE: To evaluate the effects of topical glycyl-L-histidyl-L-lysine tripeptide-copper complex (TCC; Iamin 2% Gel; Procyte Corporation, Redmond, WA) on healing in ischemic open wounds. STUDY DESIGN: Experimental study. SAMPLE POPULATION: Twenty-four adult male Sprague-Dawley rats. METHODS: Rats were divided into 3 groups: topical TCC, topical TCC vehicle (hydroxypropyl-methylcellulose), and no treatment (control). Six-mm-diameter, full-thickness wounds were created within an ischemic bipedicle skin flap on the dorsum of each rat. Each day, for 13 days, wound margins were traced, and the TCC and TCC vehicle groups were treated topically. Tracings were scanned, and wound perimeter and area were calculated. On days 6, 10, and 13, selected wounds were biopsied and analyzed for tumor necrosis factor alpha (TNF-alpha) and matrix metalloproteinases (MMP) 2 and 9. RESULTS: A significant decrease in wound area was seen in the TCC group, but not the vehicle group, when compared with the control group on days 3 to 5, 6 to 9, and 11 to 13 and when TCC was compared with TCC vehicle on days 3 and 9. On day 13, initial wound area had decreased by 64.5% in the TCC group, 45.6% in the vehicle group, and 28.2% in the control group. On days 6, 10, and 13, TCC-treated wounds contained significantly lower concentrations of TNF-alpha and MMP-2 and MMP-9 than control wounds. CONCLUSION: Topical TCC resulted in accelerated wound healing in ischemic open wounds. CLINICAL RELEVANCE: Topical TCC is an effective stimulant of healing of ischemic open wounds in rats and may have an application for the treatment of chronic wounds in other species. Clinical evaluation of topical TCC is warranted.     

Antimicrobial-induced endotoxin and cytokine activity in an in vitro model of septicemia in foals

OBJECTIVE: To determine which antimicrobials that are used to treat neonatal foals with septicemia attributable to Escherichia coli will minimize endotoxin release from bacteria and subsequent activity of inflammatory mediators while maintaining bactericidal efficacy. SAMPLE POPULATION: Blood samples from 10 healthy foals. PROCEDURE: Escherichia coli isolates A and B were isolated from 2 septicemic foals, and minimal inhibitory concentrations (MIC) were determined for 9 antimicrobials. Five of these antimicrobials were tested in vitro at 2 and 20 times their respective MIC. Whole blood or mononuclear cells grown in tissue-culture media were incubated with 105 colony-forming units of E. coli and each antimicrobial or saline (0.9% NaCl) solution. After 6 hours, number of viable bacteria remaining was determined, and supernatant was tested for endotoxin and tumor necrosis activity. RESULTS: Testing in whole blood was compromised by bactericidal effects of the blood itself. In mononuclear cell suspensions, each antimicrobial significantly reduced the number of viable bacteria to low or undetectable amounts. Antimicrobials did not differ significantly in efficacy of bacterial killing. Amikacin used alone or in combination with ampicillin resulted in significantly less endotoxin activity than did ampicillin, imipenem, or ceftiofur alone. There was a correlation between TNF-alpha and endotoxin activity. CONCLUSIONS AND CLINICAL RELEVANCE: Aminoglycosides appear less likely to induce endotoxemia and TNF-alpha synthesis during bactericidal treatment of E. coli septicemia, compared with beta-lactam antimicrobials. Use of ampicillin, imipenem, or ceftiofur in the treatment of septicemic neonatal foals should be accompanied by appropriate treatment for endotoxemia.     

Ultrasonographic and histologic evaluation of medial and middle patellar ligaments in exercised horses following injection with ethanolamine oleate and 2% iodine in almond oil

OBJECTIVE: To describe the ultrasonographic and quantitative histologic effect of injecting 2% iodine in almond oil (IAO) and ethanolamine oleate (EO) in the medial and middle patellar ligaments of horses and to determine whether a difference in response exists between IAO and EO treatment. ANIMALS: 10 healthy horses. PROCEDURE: In 5 horses, the medial and middle patellar ligaments of 1 limb were injected with EO, whereas IAO was injected in the medial and middle patellar ligaments of another 5 horses. Ultrasonographic evaluation was performed on the experimental and control limb before injection of IAO and EO and prior to euthanasia to determine cross-sectional area and evaluate fiber pattern. The patellar ligaments were harvested 2 weeks after injection and examined histologically to evaluate the inflammatory response, fibroplasia, and chondroid metaplasia. RESULTS: Injection of the patellar ligaments with IAO resulted in a greater increase in cross-sectional area on ultrasonography than EO. Both agents caused a decrease in echogenicity of the ligament. Histologically, significantly greater infiltration of inflammatory cells and fibroplasia developed after injection with IAO, compared with EO. Both agents resulted in significantly greater fibroplasia relative to control specimens. CONCLUSIONS AND CLINICAL RELEVANCE: Injection of the medial and middle patellar ligaments with IAO induces more severe inflammation and fibroplasia than EO. Maturation of the inflammatory and fibrous response may contribute to resolution or attenuation of upward fixation of the patella by subsequent stiffening of the ligaments.     

Effects of short-term trimethoprim-sulfamethoxazole administration on thyroid function in dogs

OBJECTIVE: To determine how rapidly trimethoprim-sulfamethoxazole affects serum total thyroxine (T4) and thyroid-stimulating hormone (TSH) concentrations in euthyroid dogs and how quickly hormone concentrations return to reference values following discontinuation of administration. DESIGN: Prospective study. ANIMALS: 7 healthy euthyroid dogs. PROCEDURE: Dogs were given trimethoprim-sulfamethoxazole (26.5 to 31.3 mg/kg [12 to 14.2 mg/lb], PO, q 12 h) for a maximum of 6 weeks. A CBC and Schirmer tear test were performed and serum total T4 and TSH concentrations were measured weekly. Administration of trimethoprim-sulfamethoxazole was discontinued if total T4 concentration was less than the lower reference limit and TSH concentration was greater than the upper reference limit or if persistent neutropenia developed. RESULTS: Six dogs had total T4 concentrations less than the lower reference limit within 3 weeks; T4 concentration was decreased after 1 week in 3 of these 6 dogs. In these 6 dogs, TSH concentration was greater than the upper reference limit within 4 weeks. In 1 dog, T4 and TSH concentrations were not affected, despite administration of trimethoprim-sulfamethoxazole for 6 weeks. Neutropenia developed in 4 dogs. In 1 dog, the neutropenia resolved while trimethoprim-sulfamethoxazole was still being administered. In the other 3, neutrophil counts returned to reference values 1 week after drug administration was discontinued. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that administration of trimethoprim-sulfamethoxazole at a dosage of 26.5 to 31.3 mg/kg, PO, every 12 hours can substantially alter serum total T4 and TSH concentrations and neutrophil counts in dogs within as short a time as a few weeks.     

Effect of general anesthesia and minor surgical trauma on urine and serum measurements in horses

OBJECTIVE: To characterize the effect of general anesthesia and minor surgery on renal function in horses. ANIMALS: 9 mares with a mean (+/- SE) age and body weight of 9+/-2 years and 492+/-17 kg, respectively. PROCEDURE: The day before anesthesia, urine was collected (catheterization) for 3 hours to quantitate baseline values, and serum biochemical analysis was performed. The following day, xylazine (1.1 mg/kg, IV) was administered, and general anesthesia was induced 5 minutes later with diazepam (0.04 mg/kg, IV) and ketamine (2.2 mg/kg, IV). During 2 hours of anesthesia with isoflurane, Paco2 was maintained between 48 and 52 mm Hg, and mean arterial blood pressure was between 70 and 80 mm Hg. Blood and urine were collected at 30, 60, and 120 minutes during and at 1 hour after anesthesia. RESULTS: Baseline urine flow was 0.92+/-0.17 ml/kg/h and significantly increased at 30 and 60 minutes after xylazine administration (2.14+/-0.59 and 2.86+/-0.97 ml/kg/h respectively) but returned to baseline values by the end of anesthesia. Serum glucose concentration increased from 12+/-4 to 167+/-8 mg/dl at 30 minutes. Glucosuria was not observed. CONCLUSIONS AND CLINICAL RELEVANCE: Transient hyperglycemia and an increase in rine production accompanies a commonly used anesthetic technique for horses. The increase in urine flow is not trivial and should be considered in anesthetic management decisions. With the exception of serum glucose concentration and urine production, the effect of general anesthesia on indices of renal function in clinically normal horses is likely of little consequence in most horses admitted for elective surgical procedures.