Pharmacokinetics and tissue residues of gentamicin in lactating cows after multiple intramuscular doses are administered

Gentamicin was administered IM to 6 healthy, mature, lactating cows at a dosage of 3.5 or 5 mg/kg of body weight every 8 hours for 10 consecutive days (total, 30 doses). Endometrial biopsies were done at 72, 136 or 144, and 216 hours after the first dose was administered. On the 10th day, just before the last dose of gentamicin was administered, blood samples (designated 10th-day base-line samples) were obtained, and serial blood samples were obtained for 144 hours after the last injection was given. The cows were catheterized on the 10th day, and urine was obtained for 10 to 18 consecutive hours. Milk samples were also obtained. The cows were slaughtered at different times after the last dose was given, and samples were taken from 22 tissues and organs. Serum, milk, urine, and tissue gentamicin concentrations were determined by radioimmunoassay. Serum gentamicin concentrations were best fitted to a 2-compartment open model. The mean half-lives for absorption, distribution, and elimination were 0.16 +/- 0.14, 2.59 +/- 0.53, and 44.91 +/- 9.38 hours, respectively. Total body clearance and renal clearance were 1.65 +/- 0.69 and 1.32 +/- 0.25 ml/min/kg, respectively. The percentage of the dose excreted unchanged in the urine at 8 hours after the last dose was given was 98 +/- 15. As expected, of the tissues examined, the gentamicin concentrations in the kidney cortex and medulla were 1,500 times greater than those in serum. Renal function remained within the baseline range during the 10 days of gentamicin treatment.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pharmacokinetics of gentamicin at steady-state in ponies: serum, urine, and endometrial concentrations

Gentamicin (GT) was administered IM to 6 healthy mature mare ponies at a dosage of 5 mg/kg of body weight every 8 hours for 7 consecutive days (total, 21 doses). Two venous blood samples were collected before (trough) and at 1 hour (peak) after the 5th, 10th, 14th, and 19th doses. An endometrial biopsy was done of each mare on days 4 and 7. On the 7th day, just before the 21st administration of GT, base-line blood samples were collected, and 22 blood samples were collected over a period of 48 hours after GT was given. The mares were catheterized on the 7th day, and urine was collected for 24 hours. Serum, urine, and endometrial GT concentrations were determined by a radioimmunoassay technique (sensitivity of 0.3 micrograms/ml of serum). Serum GT concentration data obtained from the terminal phase were best fitted by a 1-compartment open model with a biological half-life of 2.13 +/- 0.43 hours. Total body clearance and renal clearance were 1.69 +/- 0.41 and 1.40 +/- 0.26 ml/min/kg, respectively. Mean endometrial concentrations on day 4 and day 7 were 5.02 +/- 3.3 and 12.75 +/- 1.6 micrograms/g. To achieve mean serum GT concentrations (micrograms/ml) at steady state of 6.47 +/- 1.51, a maximum steady-state concentration of 12.74 +/- 1.60, and a minimum steady-state concentration of 1.43 +/- 0.57, a dosage of 5 mg/kg every 8 hours is recommended. Serum urea nitrogen, serum creatinine, and the fractional clearance of sodium sulfanilate were determined before and after GT treatment. Renal function remained within the base-line range during 7 days of GT administration.     

Kinetic study of serum gentamicin concentrations in baboons after single-dose administration

This study establishes preliminary pharmacokinetic data on the use of gentamicin sulfate administered IM to baboons. Serum concentrations greater than or equal to 12 micrograms/ml are generally agreed to cause toxicosis in human beings. On the basis of preliminary test results suggesting that the manufacturer's recommended dosage for dogs of 4.4 mg/kg of body weight caused potentially toxic serum concentrations, a dosage of 3 mg/kg was chosen to conduct a single-dose kinetic study in 6 baboons. Using a single-compartment model, the gentamicin serum half-life for IM administration of 3 mg of gentamicin/kg was 1.58 hours, and serum concentrations remained below the potentially toxic concentrations reported for human beings. We suggest that a dosage of 3 mg/kg is safer than a dosage of 4.4 mg/kg administered IM to baboons. Minimal inhibitory concentrations for 2 Pseudomonas aeruginosa isolates were less than or equal to 1 micrograms/ml. On the basis of our measured elimination half-life of 1.58 hours, it is reasonable to suppose that dosing q24 h will be inadequate to maintain therapeutic serum concentrations. We calculate that serum concentrations will remain at or above our measured minimal inhibitory concentration for P aeruginosa (1 micrograms/ml) for 100% of the treatment time if the animal is dosed q 6h, 78% for dosing q 8h, and 52% for dosing q 12h. Therefore, we suggest 3 mg/kg, q 8h or q 6h as appropriate dosing schedules for the use of gentamicin sulfate administered IM to baboons.     

Gentamicin Nephrotoxicity – A Comparison of In Vitro Findings with In VivoExperiments in Equines

The aminoglycoside gentamicin is often used in equine practice. Despite its clinical use, concerns remain regarding the potential toxic side-effects, such as nephrotoxicity, in equine patients, particularly after repeated dosing. The aim of the study was to investigate first in vitro the mechanisms contributing to the renal toxicity of gentamicin and to identify sensitive biomarkers indicating proximal tubule damage. To this end, the kidney-derived cell lines LLC-PKI and MDCK were treated with gentamicin at different concentrations. Toxicity was assessed by measuring the release of gamma-glutamyl transferase (GGT), and the production of reactive oxygen species (ROS). Cell viability was measured using Alamar blue (AB) and Neutral red (NR) cytotoxicity assays. Gentamicin exerted a dose-dependent toxicity. Primarily, loss of brush border membrane integrity, indicated by GGT leakage, and an increased ROS production were observed. As GGT was found to be a sensitive marker for gentamicin-induced renal cell injury, in the subsequent in vivo experiments, in which ponies were given gentamicin (3.0 mg/kg bw three times daily and 4.5 mg/kg bw twice daily) for five consecutive days, plasma levels and the urinary excretion of GGT and creatinine were measured and the GGT:creatinine ratio was calculated. Elevated GGT levels in urine following gentamicin therapy were observed, but this enzyme leakage was transient and returned to baseline values after cessation of therapy. It could thus be concluded that even a conservative dose regimen of gentamicin did not result in significant renal toxicity in healthy ponies.     

Acute experimentally induced aflatoxicosis in the weanling pony

Nineteen weanling ponies and 1 adult pony were given a single oral dose of aflatoxin B1 (AFB1). Dosages were: 0, 0.5, 1, 2, 4, 5, 6, and 7.4 mg of AFB1/kg of body weight. Vital signs were monitored, and whole blood and serum collected for analysis of serum enzymes, prothrombin time, blood cell counts, and serum urea nitrogen. Ponies that died were examined for gross lesions, and tissues were collected for histopathologic examination and analysis of AFB1 and AFM1 residues. Two of the 4 ponies given the 2 mg/kg dose and all ponies given the larger dosages died within 76 hours. Clinical signs included increased rectal temperature, faster heart and respiratory rates, abdominal straining, bloody feces, and tetanic convulsions. At necropsy, ponies that died of acute aflatoxicosis showed visceral petechiae and hepatic focal lesions. Histopathologic changes included severe hepatic necrosis, vacuolation, and bile duct hyperplasia. Aflatoxins B1 and M1 were recovered from liver, kidney, skeletal muscle, and gastrointestinal contents. One other pony given the 2 mg/kg dose died 32 days after dosing, and 1 control pony died after 70 days. Continuous elevations in prothrombin time and serum aspartate aminotransferase, alanine aminotransferase, and gamma-glutamyl transpeptidase levels were observed in ponies dosed at 4 mg/kg or more. Significant (P less than 0.05) elevations in these values, which peaked 2 to 3 days after dosing, were seen in ponies given the 2 mg/kg dose. This group also had significant increases over controls in PCV and hemoglobin concentration 5 days after dosing.     

Single intravenous and multiple intramuscular dose pharmacokinetics and tissue residue profile of gentamicin in sheep

Single and multiple dose gentamicin regimens were compared in sheep to determine the relevant pharmacokinetic differences. Seven mature sheep were given 10 mg/kg of gentamicin by IV bolus. Serum concentrations were monitored for 19 days. Four weeks after the initial bolus, gentamicin was administered IM (3 mg/kg every 8 hours) for 7 days. Ewes were euthanatized and necropsied at 1, 8, and 15 days after termination of the IM regimen and the tissues were assayed for gentamicin. Serum concentrations were analyzed using a triexponential equation. The IV kinetic studies revealed an alpha half-life (t1/2) of 0.31 +/- 0.14 hours, beta t1/2 of 2.4 +/- 0.5 hours, and gamma t1/2 of 30.4 +/- 18.9 hours. Multiple IM dose kinetic studies revealed a beta t1/2 of 2.8 +/- 0.6 hours and gamma t1/2 of 82.1 +/- 17.8 hours. After multiple dosing, gamma t1/2 was significantly longer than after the single IV bolus (P less than 0.05). Twenty-four hour urine collection accounted for 75% to 80% of the total IV dose. Renal cortical gentamicin concentration reached 224 micrograms/g of tissue and then decreased, with a 90-hour t1/2. Renal medullary gentamicin concentration reached 18 micrograms/g with a 42-day t1/2. After multiple dosing, liver gentamicin concentration reached 11 micrograms/g and skeletal muscle concentrations were less than or equal to 0.6 micrograms/g. Route or duration of administration significantly affected the gamma-phase serum concentrations, which may influence gentamicin nephrotoxicosis. The present study also illustrated the complexities in predicting aminoglycoside withdrawal times for food-producing animals before slaughter.     

Phenolsulfonphthalein pharmacokinetics and renal morphologic changes in adult pony mares with gentamicin-induced nephrotoxicosis

Changes in renal function, determined by pharmacokinetics of phenolsulfonphthalein (PSP), and renal morphologic features were examined in adult pony mares given 20 mg of gentamicin sulfate/kg of body weight, IV, q 8 h (group A) n = 7 or isotonic saline solution, IV, q 8 h, n = 5 (group B) for 14 days. Susceptibility of ponies to gentamicin-induced nephrotoxicosis was varied. Two group-A ponies developed acute renal failure and were euthanatized before treatment day 14, whereas 5 group-A A ponies did not develop physical or behavioral abnormalities after 14 days of gentamicin administration. All group-A ponies but none of group-B ponies developed ultrastructural abnormalities of the proximal tubular epithelium, consistent with gentamicin-induced nephrotoxicosis. Significant (P less than 0.05) differences were not detected in pharmacokinetic values of either group. Clearance of PSP was reduced in 4 group-A ponies that developed the most severe gentamicin-induced nephrotoxicosis. Changes in clearance of PSP were significantly (P less than 0.05) correlated with changes in the serum creatinine concentration.     

Urinary gamma-glutamyl transpeptidase activity in dogs with gentamicin-induced nephrotoxicity

Serum creatinine concentrations, 24-hour endogenous creatinine clearance, and 24-hour urinary gamma-glutamyl transpeptidase (UGGT) activity were measured daily in 6 dogs given nephrotoxic dosages of gentamicin (10 mg/kg of body weight) every 8 hours for 10 days. Mean UGGT activity was significantly increased by day 5 (P less than 0.05) and preceded significant increases in serum creatinine values (greater than 2.0 mg/dl) observed on day 9. Endogenous creatinine clearance remained within normal limits (2.98 +/- 0.96 ml/min/kg) until day 8. Urinalyses performed 8 days after initiation of gentamicin treatment indicated renal tubular damage (granular casts) in 1 of the 6 dogs, and glucosuria in 3 of the 6 dogs. Measurement of UGGT activity was a more sensitive and reliable method of assessing acute renal tubular damage induced by gentamicin than were serum creatinine concentrations or 24-hour endogenous creatinine clearance.     

Pharmacokinetics of single-dose intravenous or intramuscular administration of gentamicin in roosters

Healthy mature roosters (n = 10) were given gentamicin (5 mg/kg of body weight, IV) and, 30 days later, another dose IM. Serum concentrations of gentamicin were determined over 60 hours after each drug dosing, using a radioimmunoassay. Using nonlinear least-square regression methods, the combined data of IV and IM treatments were best fitted by a 2-compartment open model. The mean distribution phase half-life was 0.203 +/- 0.075 hours (mean +/- SD) and the terminal half-life was 3.38 +/- 0.62 hours. The volume of the central compartment was 0.0993 +/- 0.0097 L/kg, volume of distribution at steady state was 0.209 +/- 0.013 L/kg, and the total body clearance was 46.5 +/- 7.9 ml/h/kg. Intramuscular absorption was rapid, with a half-life for absorption of 0.281 +/- 0.081 hours. The extent of IM absorption was 95 +/- 18%. Maximal serum concentration of 20.68 +/- 2.10 micrograms/ml was detected at 0.62 +/- 0.18 hours after the dose. Kinetic calculations predicted that IM injection of gentamicin at a dosage of 4 mg/kg, q 12 h, and 1.5 mg/kg, q 8 h, would provide average steady-state serum concentrations of 6.82 and 3.83 micrograms/ml, with minimal steady-state serum concentrations of 1.54 and 1.50 micrograms/ml and maximal steady-state serum concentrations of 18.34 and 7.70 micrograms/ml, respectively.     

Induction of estrus in greyhound bitches with prolonged idiopathic anestrus or with suppression of estrus after testosterone administration

Twelve anestrous adult Greyhound bitches were used to study a regimen for induction of estrus. Once daily, 7 bitches were given diethylstilbestrol (DES; 5 mg, PO) until sanguineous vaginal discharge and vulvar edema were observed (designated as day 1 of proestrus) and for 2 days thereafter. If no response was elicited after 7 days, a doubled DES dose was given for up to an additional 7 days. Luteinizing hormone (5 mg, IM) was given on day 5 of proestrus, and follicle-stimulating hormone (10 mg, IM) was given on days 9 and 11 of proestrus. Bitches were bred once on day 13. Five bitches were used as a control group; they were given candy tablets for 7 days (first day on tablets, treatment day 1) and 0.9% NaCl (1.0 ml, IM) on treatment days 12, 16, and 18. The 7 bitches treated with DES had a mean proestrus period of 7.7 days and a mean estrus period of 5.7 days up to the day of mating. After mating, they had a mean gestation interval of 64 days and delivered a mean of 4 pups/litter. In 5 bitches, initial treatment with 5 mg of DES/day induced proestrus within 7 days; however, in 2 bitches, additional treatment with 10 mg of DES/day was needed for 5 and 6 days, respectively. Serum estradiol-17 beta and progesterone concentrations remained at base line during the period of DES treatment. Concentrations of both hormones increased after injection with luteinizing hormone and remained high for the next 4 days.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of dose and duration of therapy on gentamicin tissue residues in sheep

The effects of different doses and dosage regimens on gentamicin pharmacokinetics and tissue residues were determined. Five groups of 12 sheep each were given gentamicin IM: group I, 2 mg of gentamicin sulfate/kg once; group II, 6 mg/kg once; group III, 18 mg/kg once; group IV, 6 mg/kg every 24 hours for 3 doses; and group V, 2 mg/kg every 8 hours for 9 doses. Serum concentrations were determined serially until sheep were killed and necropsied. Three sheep from each group were killed at 1, 4, 8, and 12 days after the last dose was administered. Renal cortex, renal medulla, liver, spleen, lung, skeletal muscle, and skeletal muscle at the injection site were assayed for gentamicin. An exponential equation was fitted to the serum concentrations, and various pharmacokinetic variables were determined. Serum clearance tended to increase as the single dose increased (P = 0.0588). Steady-state volume of distribution increased as the single dose was increased (P less than 0.05). Renal cortex contained the highest concentration of gentamicin which decreased in a biexponential manner. Concentrations in all tissues, except the injection site, were dependent upon the amount of the total dose, not the size of the injected dose (P less than 0.05). Concentrations at the injection site were up to 29 micrograms/g of tissue at 1 day after the last dose was given and were dependent upon the amount of total dose from multiple injections, not on the amount of each injected dose (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Nephrotoxicity in Goats Caused by Dosing with a Water Extract from the Stems of Narthecium Ossifragum Plants

Seven goats were given a single dose of an aqueous extract derived from 30 g (wet weight) of Narthecium ossifragum per kg liveweight. Their serum creatinine and urea concentrations increased to day 5 but then fell to normal by day 10. Serum magnesium increased to day 4 and decreased to normal by day 9. Their serum calcium concentration was lower than normal on days 4, 5 and 6. Histopathological examination of the kidneys of goats killed or found dead 2, 4, 6, 8, 11 or 16 days after dosing revealed tubular epithelial cell degeneration and necrosis. Regeneration of the tubular epithelium and signs of interstitial fibroplast proliferation and fibrosis could be seen in animals killed on days 8, 11, 16 and 42. No signs of liver damage were observed in 3 goats dosed with the insoluble plant material from 40 g (wet weight) Narthecium ossifragum per kg liveweight. The total dose was divided into three doses, which were given intraruminally within 7 h. The activities of aspartate aminotransferase, -glutamyl-transferase and glutamate dehydrogenase remained within the normal range in all 10 goats after dosing.     

Imidocarb and parvaquone in the treatment of piroplasmosis (Babesia equi) in equids

The therapeutic efficacies of imidocarb and parvaquone were tested against Babesia equi of European origin in carrier horses and for induced acute infections in splenectomized ponies. Imidocarb, at a dosage of 4 mg/kg of body weight, given IM at 72-hour intervals 4 times, was ineffective in eliminating B equi-carrier infection in 9 mature geldings. A single IM administration of 4 mg/kg was not therapeutic in acutely infected splenectomized ponies. When given at 3 different dosages and treatment schedules, parvaquone was ineffective in clearing carrier infection. Parvaquone given IM once at a dosage of 20 mg/kg was effective for acute B equi infections in splenectomized ponies; parasitemia began to decrease within 24 hours after treatment. Infections were not eliminated however, and within 4 weeks, secondary parasitemia and anemia developed. Of 4 ponies, 3 died of acute piroplasmosis.     

Evaluations of buparvaquone as a treatment for equine babesiosis (Babesia equi)

We evaluated the efficacy of buparvaquone in eliminating Babesia equi of European origin in carrier horses and in experimentally infected splenectomized ponies. When administered at the rate of 2.5 mg/kg of body weight, IM, 4 times at 96-hour intervals, buparvaquone was effective in eliminating B equi carrier infection in 1 horse. Such results could not be repeated at the same dosage or at 3.5 or 5 mg/kg, IM. Buparvaquone given at the rate of 4 to 6 mg/kg IV and/or IM was therapeutically effective in 4 of 5 acute B equi infections in splenectomized ponies. The treated ponies became carriers.     

Combined pharmacokinetics of gentamicin in pony mares after a single intravenous and intramuscular administration

Healthy mature pony mares (n = 6) were given a single dose of gentamicin (5 mg/kg of body weight) IV or IM 8 days apart. Venous blood samples were collected at 0, 5, 10, 20, 30, and 45 minutes and at 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 18, 24, 30, 36, 40, and 48 hours after IV injection of gentamicin, and at 10, 20, 30, and 45 minutes and at 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 18, 24, and 30 hours after IM injection of gentamicin. Gentamicin serum concentration was determined by a liquid-phase radioimmunoassay. The combined data of IV and IM treatments were analyzed by a nonlinear least-square regression analysis program. The kinetic data were best fitted by a 2-compartment open model, as indicated by residual trends and improvements in the correlation of determination. The distribution phase half-life was 0.12 +/- 0.02 hour and postdistribution phase half-life was 1.82 +/- 0.22 hour. The volume of the central compartment was 115.8 +/- 6.0 ml/kg, volume of distribution at steady state was 188 +/- 9.9 ml/kg, and the total body clearance was 1.27 +/- 0.18 ml/min/kg. Intramuscular absorption was rapid with a half-life for absorption of 0.64 +/- 0.14 hour. The extent of absorption was 0.87 +/- 0.14. Kinetic calculations predicted that IM injections of 5 mg of gentamicin/kg every 8 hours would provide average steady-state serum concentrations of 7.0 micrograms/ml, with maximum and minimum steady-state concentrations of 16.8 and 1.1 micrograms/ml, respectively.     

Acid-base and electrolyte alterations associated with salivary loss in the pony

Esophageal fistulas were made in 6 ponies to evaluate whole blood acid-base values and serum and salivary electrolyte alterations associated with salivary depletion. Acid-base and electrolyte values remained within normal ranges for 15 days in 3 control ponies fed a pelleted diet through nasogastric tubes. In 6 ponies with esophageal fistulas that were fed the same diet through esophagostomy tubes, hypochloremia and hyponatremia developed during the same period. Serum K concentrations were only marginally depleted, probably because of dietary replacement. Salivary depletion resulted in transient metabolic acidosis from bicarbonate lost in saliva followed by progressive metabolic alkalosis. The alkalosis probably resulted from renal compensation of electrolyte imbalances. Salivary electrolytes were in high concentrations, probably because of increased salivary flow rates. Initial saliva was rich in Na, Cl, and K, but progressive reduction in salivary Na and Cl concentrations occurred during the 5-day collection period. These electrolyte savings could be explained by dietary influences and hormonal control of electrolyte transport in salivary ducts. Therapy for correction of acid-base and electrolyte alterations was also discussed.     

Adverse effects of gentamicin in scarlet macaws and galahs

The adverse effects of administration of gentamicin (5 mg/kg of body weight, IM, q 12 h) for 7 days were studied in healthy scarlet macaws (Ara macao) and galahs (Eolophus roseicapillus; cockatoos). Polydipsia and polyuria developed in each species, but were greater and persisted longer in the cockatoos. Peak water intake in the cockatoos more than quadrupled, and remained increased for 23 days after cessation of gentamicin administration. Plasma aspartate transaminase activity increased significantly (P less than 0.05) after treatment in the macaws, and plasma aspartate transaminase and lactate dehydrogenase activities increased in the cockatoos. Single IM administration of gentamicin (5 mg/kg) resulted in mean (+/- SEM) plasma concentration of 20.6 (+/- 1.85) micrograms/ml at 0.5 hour for either species of birds. There were no significant differences between mean plasma gentamicin concentrations for cockatoos and macaws at any time after drug administration, except at 12 hours, when values for cockatoos were significantly (P less than 0.05) greater than those for macaws. The elimination half-life for gentamicin after IM administration of 5 and 10 mg/kg was 1.17 and 1.07 hours, respectively, for macaws and 1.23 and 1.44 hours, respectively, for cockatoos. Correlation between drug disposition and adverse side effects could not be detected.     

Bioavailability of gentamicin in dogs after intramuscular or subcutaneous injections

Healthy adult mixed-breed dogs, assigned to 2 groups of 6 dogs each, were given 3 mg of gentamicin sulfate/kg of body weight on 3 injection days 7 days apart. Group 1 was given gentamicin by rapid IV injection, by injection into the belly of the longissimus muscle at the first lumbar vertebrae (IM site 1), and by injection in the belly of the biceps femoris muscle (IM site 2). Group 2 was given gentamicin by rapid IV injection, by SC injection into the space over the cranial angle of the scapula on the midline (SC site 1), and by SC injection just caudal to the crest of the ilium (SC site 2). Pharmacokinetic values (mean +/- SD) from 12 dogs given gentamicin IV were 54.4 +/- 15.4 minutes for the effective half life, 2.29 +/- 0.48 ml/kg/min for clearance, and 172 +/- 25.4 ml/kg for volume of distribution at steady state. Bioavailability (93.92 to 96.65%) and peak plasma gentamicin concentration (9.43 to 10.89 micrograms/ml) were independent of injection site, but time to peak concentration when gentamicin was given at SC site 2 (43.33 minutes) was significantly (P less than 0.05) longer than that when gentamicin was given at IM site 1 (27.50 minutes). Absorption half-life was shorter after injections were given at both IM sites (8.9 and 9.8 minutes) than after injection was given at SC site 2 (18 minutes).     

The effect of exploratory laparotomy on the serum and peritoneal haptoglobin concentrations of the pony.

Serum haptoglobin concentration was used as an indicator of the acute phase response in ponies undergoing exploratory laparotomy. Preoperative, 1 h intraoperative, 3 h, 6 h, 12 h and 24 h postoperative blood samples and 48 h postoperative peritoneal fluid samples were obtained for haptoglobin analysis. A spectrophotometric assay based on cyanmethemoglobin binding capacity (CyanBC) was used to determine haptoglobin concentrations. The preoperative reference range for serum haptoglobin concentrations in these ponies was 25-60 mg CyanBC/dL. Intraoperative and 3 h postoperative blood samples had decreased haptoglobin concentrations when compared to preoperative values. Serum haptoglobin concentrations began to rise by the 6 h postoperative sample and were generally elevated above preoperative values by the 24 h postoperative sample. Two of the ten ponies had mild signs of postoperative colic which were associated with twofold elevations in serum haptoglobin concentrations and fivefold elevations in peritoneal fluid haptoglobin concentrations.     

Serum lipid and lipoprotein changes in ponies with experimentally induced liver disease

Alterations in serum lipid and lipoprotein concentrations in ponies with experimentally induced liver disease were investigated. Hepatocellular damage was induced, using a nonlethal dose of carbon tetrachloride. In a separate group of ponies, obstructive jaundice was induced by surgical ligation of the common bile duct. Over a 6-day period, blood samples were obtained from ponies after treatment with carbon tetrachloride and for 12 days in ponies subjected to surgery. Serum cholesterol and triglyceride concentrations were unaffected in both groups of ponies, except for significantly (P less than 0.01) high triglyceride concentration in ponies of the ligated group during the second postsurgical week. This increase was most likely attributable to anorexia observed during that period. Hyperbilirubinemia was observed early in ponies of the ligated group; most of the bilirubin was of the conjugated type. Using electrophoretic and ultracentrifugal methods, serum lipoprotein alterations were detected only in ponies of the ligated group. Increases of very low-density and low-density lipoprotein cholesterol concentrations and decrease in high-density lipoprotein cholesterol concentration were found. Although no changes were seen in total serum cholesterol concentration, a redistribution of lipoprotein cholesterol was observed in ponies of the ligated group. Similar alterations in lipoprotein distribution have been found in dogs, rats, and human beings with obstructive jaundice and cholestasis. The association between serum lecithin:cholesterol acyl transferase activities and these lipoprotein alterations remains to be elucidated.