Twenty-four horses were randomly allocated to 3 groups. Horses were anesthetized, subjected to a ventral midline celiotomy, and the large colon was exteriorized and instrumented. Group-1 horses served as sham-operated controls. Group-2 horses were subjected to 6 hours of low-flow colonic arterial ischemia, and group-3 horses were subjected to 3 hours of ischemia and 3 hours of reperfusion. Baseline (BL) samples were collected, then low-flow ischemia was induced by reducing ventral colonic arterial blood flow to 20% of BL. All horses were monitored for 6 hours after BL data were collected. Blood samples were collected from the colonic vein and main pulmonary artery (systemic venous (SV) for measurement of plasma endotoxin, 6-keto prostaglandin F1alpha (6-kPG), thromboxane B2 (TXB2), and prostaglandin E2 (PGE2) concentrations. Tumor necrosis factor and interleukin-6 activities were measured in colonic venous (CV) serum samples. Data were analyzed, using two-was ANOVA, and post-hoc comparisons were made, using Dunnett's and Tukey's tests. Statistical significance was set at P < 0.05 Endotoxin was not detected in CV or SV plasma at any time. There was no detectable tumor necrosis factor or interleukin-6 activity in CV samples at any time. There were no differences at BL among groups for CV or SV 6-kPG, PGE2, or TXB2 concentrations, nor were there any changes across time in group-1 horses. Colonic venous 6-kPG concentration increased during ischemia in horses of groups 2 and 3; CV 6-kPG concentration peaked at 3 hours in group-3 horses, then decreased during reperfusion, but remained increased through 6 hours in group-2 horses. Systemic venous 6-kPG concentration increased during reperfusion in group-3 horses, but there were no changes in group-2 horses. Colonic venous PGE2 concentration increased during ischemia in horses of groups 2 and 3, and remained increased for the first hour of reperfusion in group-3 horses and for the 6-hour duration of ischemia in group-2 hors.

Keratan sulfate (KS) is a glycosaminoglycan, distribution of which is confined mostly to hyaline cartilage. As such, it is a putative marker of hyaline cartilage catabolism. In experiment 1, a focal osteochondral defect was made arthroscopically in 1 radial carpal bone of 2 ponies, and in 2 other ponies, chymopapain was injected into the radiocarpal joint to induce cartilage catabolism. Sequential and concurrent plasma and synovial fluid concentrations of KS were measured, up to 13 months after induction of cartilage injury, to determine whether changes in KS concentrations reflected cartilage catabolism. In experiment 2, a large, bilateral osteochondral defect was made in the radial carpal bones of 18 ponies, which were subsequently given postoperative exercise and/or injected intra-articularly with 250 mg of polysulfated glycosaminoglycan (PSGAG). Medication was given at surgery, then weekly for 4 weeks. Blood samples were collected and synovial fluid was aspirated before surgery, when medication was given, and at postmortem examination (postoperative week 17). The KS concentration was measured in these fluids to determine whether changes in KS concentration indicated an effect of joint treatment. In experiment 1, the concentration of KS in synovial fluid was highest 1 day after joint injury, and the concentration in plasma peaked 2 days after joint injury. For ponies receiving chymopapain intra-articularly (generalized cartilage catabolism), a fivefold increase over baseline was observed in the concentration of KS in plasma (peak mean, 1.2 microgram/ml), and a tenfold increase over baseline in synovial fluid (peak mean, 2.0 mg/ml) was observed. On average, these maxima were threefold higher than values in fluids of ponies with osteochondral defects (focal cartilage disease). In experiment 2, nonexercised ponies had lower KS concentration (as a percentage of the preoperative concentration) in synovial fluid than did exercised ponies at all postoperative times, and.

Renal clearance procedures were performed on adult mixed-breed dogs with a wide range of renal function. Endogenous creatinine clearance was computed after analyzing plasma and urine for creatinine by use of 2 methods, PAP and kinetic Jaffe. For 20-minute clearance procedures, [14C]inulin clearance was measured simultaneously with endogenous creatinine clearance. For 111 twenty-minute clearance procedures performed on 24 dogs, [14C]inulin clearance was highly correlated with creatinine clearance for both methods of creatinine analysis (R2 = 0.979 for [14C]inulin-PAP; R2 = 0.943 for [14C]inulin-Jaffe). The absolute values for PAP and [14C]inulin clearance were nearly the same (PAP-to-[14C]inulin clearance ratio = 1.03 +/- 0.08), but those for Jaffe clearance were substantially less than those for [14C] inulin clearance Jaffe-to-[14C]inulin clearance ratio = 0.88 +/- 0.10). The Jaffe-to-[14C] inulin clearance ratio was inversely correlated with degree of renal function (R2 = 0.464), whereas the PAP-to-[14C]inulin clearance ratio was not correlated with degree of renal function (R2 = 0.060). Thus, Jaffe-determined creatinine clearance varied, in relation to [14C] inulin clearance, depending on degree of renal function. In 4 clinically normal dogs, 20-minute and 24-hour sample collections analyzed by use of the PAP method gave clearance values significantly greater, for both periods, than did Jaffe analyses. The PAP-determined creatinine clearance values were less than, but not significantly different from 20-minute exogenous creatinine clearance values determined 10 days after 24-hour collections. For 20-minute and 24-hour collections, the difference in clearance values between the PAP and Jaffe methods was attributable mostly to lower plasma creatinine values for the PAP method (mean +/- SEM, plasma PAP-to-Jaffe ratio = 0.798 +/- 0.053). However, urine creatinine values also were less by use of the PAP method.

Epidemiologic relations were evaluated between plasma concentrations of nutrients and cardiovascular diseases. A total of 220 cats were assessed: 144 cats with noninduced acquired heart disease and 76 clinically normal cats. Plasma was assayed for taurine, alpha-tocopherol, selenium, retinol, and total cholesterol and triglycerides concentrations. Cardiovascular disease groups included dilated cardiomyopathy (n = 53), left ventricular hypertrophy (n = 28), hyperthyroidism (n = 11), and uncertain classification (n = 52). In cats with dilated cardiomyopathy, mean plasma taurine concentration was the lowest of that in cats of any group, being only 38% of the value in healthy cats; females had less than half the mean value of males. Tocopherol concentration was 20% lower than normal, and retinol concentration was 40% higher than normal. Total cholesterol concentration was 36% lower than normal. Triglycerides concentration was higher in these cats than in any other group-twice the value recorded in healthy cats and 67% higher than that in hyperthyroid cats. In cats with hypertrophic cardiomyopathy, almost 15% had mean plasma taurine concentration < 30 micromol/L. Retinol concentration was 15% higher, and triglycerides concentration was 54% higher than normal. Approximately 27% of hyperthyroid cats had mildly decreased plasma taurine concentration. Hyperthyroid cats had the lowest tocopherol and cholesterol values; both were at least 30% lower than normal. Retinol concentration was 30% higher than Approximately 14% of cats with uncertain classification had mildly decreased plasma taurine concentration. Plasma retinol and triglycerides concentrations were higher than normal in 25 and 38% of these cats, respectively. Plasma selenium concentration, compared between healthy cats and cats with cardiac disease, was not significantly different. This observation may not be meaningful, however, in light of the limited number of cats in which selenium was assessed.

Because hepatocyte-stimulating factor/interleukin 6 (IL-6) 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 < 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/kg 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.

Concentrations of total, free, and esterified carnitine were determined in plasma, liver, and skeletal muscle from cats with idiopathic hepatic lipidosis and compared with values from healthy cats. The mean concentrations of plasma, liver, and skeletal muscle total carnitine; plasma and skeletal muscle free carnitine; and plasma and liver esterified carnitine were greater (P < 0.05) in cats with idiopathic hepatic lipidosis than in control cats. The mean for the ratio of free/total carnitine in plasma and liver was lower (P < 0.05) in cats with idiopathic hepatic lipidosis than in control cats. These data suggest that carnitine deficiency does not contribute to the pathogenesis of feline idiopathic hepatic lipidosis.

Oxytetracycline (OTC) pharmacokinetic values in plasma and bile were ascertained after IV administration of the drug. At 6 hours after administration of 1 mg of OTC/kg of body weight, 2.15% of the dose was found in the bile and 37.6% was found in the urine. At 2 hours after administration, the peak bile-to-plasma OTC concentration ratio was 60:1. Bioavailability of OTC was 47.6% when it was administered orally to fasted turkeys and was 9.4% when administered to fed turkeys.

Adrenocortical function was assessed in 27 Beagle pups at 2, 4, 6, 8, 10, and 12 weeks of age by determination of plasma sodium, potassium, and chloride concentrations; serum aldosterone and cortisol concentrations; and plasma ACTH concentrations. Serum cortisol concentration was measured before and 1 and 2 hours after IM administration of 2.2 IU of ACTH/kg of body weight. Serum progesterone concentration also was determined for all pups at 2, 4, and 6 weeks of age. Mean baseline cortisol concentration was lower for pups 8 weeks old or younger than for mature dogs. Nevertheless, mean serum ACTH-stimulated cortisol concentration in dogs of all age groups increased into the adult reference range after administration of ACTH. For pups 4 weeks old or younger, increase in cortisol concentration was maximal at 2 hours after ACTH administration. However, in pups between 6 and 12 weeks of age, the increase in cortisol concentration was maximal 1 hour after ACTH administration in about a third of the pups, whereas the remaining pups had peak values at 2 hours. Mean plasma sodium, potassium, and chloride concentrations for each age group were within the reference ranges established for mature dogs, with the exception of lower mean plasma sodium and chloride concentrations in pups 4 weeks old or younger. Mean serum aldosterone concentration in pups of each age group was substantially higher than the range of aldosterone concentrations for clinically normal mature dogs. Median progesterone concentration was uniformly less than 0.2 ng/ml for all pups 6 weeks old or younger. The normal endogenous ACTH concentration and adequate cortisol responses to exogenous ACTH seen in our pups would support functional pituitary gland and adrenal cortex for cortisol production. The low baseline cortisol concentration observed in the pups of this study may be related to reduced binding of cortisol to plasma proteins, as exists in human infants.

Hyperxanthinuria and xanthine uroliths have been recognized with increased frequency in dogs with ammonium urate uroliths that had been given allopurinol. We hypothesized that dietary modification might reduce the magnitude of uric acid and xanthine excretion in urine of dogs given allopurinol. To test this hypothesis, excretion of metabolites, volume, and pH were determined in 24-hour urine samples produced by 6 healthy Beagles during periods of allopurinol administration (15 mg/kg of body weight, PO, q 12 h) and consumption of 2 special purpose diets: a 10.4% protein (dry matter), casein-based diet and a 31.4% protein (dry matter), meat-based diet. Significantly lower values of uric acid (P = 0.004), xanthine (P = 0.003), ammonia (P = 0.0002), net acid (P = 0.0001), titratable acid (P 0.0002), and creatinine (P = 0.01) excreted during a 24-hour period were detected when dogs consumed the casein-based diet and were given allopurinol, compared with the 24-hour period when the same dogs consumed the meat-based diet and were given allopurinol. For the same 24-hour period, urine pH values, urine volumes, and urine bicarbonate values were significantly (P = 0.0004, P 0.04, and P = 0.002, respectively) higher during the period when the dogs were fed the casein-based diet and given allopurinol than when they were fed the meat-based diet and given allopurinol. Endogenous creatinine clearance was significantly (P = 0.006) lower when dogs were fed the casein-based diet and given allopurinol than when they were fed the meat-based diet and given allopurinol. Significantly lower concentrations of plasma uric acid (P 0.0001), plasma xanthine (P = 0.01), and serum urea nitrogen (P = 0.0001) were detected when dogs consumed the casein-based diet and were given allopurinol than when they consumed the meat-based diet and were given allopurinol.