Antithrombin III activity (residual thrombin activity) in plasma from non-medicated or heparinized horses

Two synthetic substrate assays (fluorometric and chromogenic) were used to measure antithrombin-III (AT-III) activity (residual thrombin activity) in non-medicated and heparin (sodium) treated horses. In 18 non-medicated horses the fluorometric substrate assay (FSA) values were similar to previous reports but they reflected inconsistent trends and larger deviations in the heparin-treated groups (Group 2: 40 and 100 U/kg IV, n=6; Group 3: 240 U/kg IV, n=5; Group 4: 80 U/kg IV followed by 160 U/kg SC, n=8) when compared to the chromogenic substrate assay (CSA) values. The CSA values for the 18 non-medicated horses indicated a higher AT-III activity (lower residual thrombin activity) than the FSA. AT-III activity was quantified in 18 non-medicated horses (29 mg/dl) and compared well with values for humans (30 mg/dl) and dogs (40 mg/dl). Plasma heparin concentrations, determined by the FSA, correlated well with the therapeutic range (1.5 fold to 2.5 fold prolongation of the activated partial thromboplastin time (APTT) normal value) and values reported for humans. The effect of heparin therapy on AT-III activity in four treatment regimens was evaluated. AT-III activity was not significantly affected (with one exception) by a single dose of intravenous (IV) heparin (40 and 100 U/kg) nor by repeated subcutaneous (SC) injections of heparin (240 U/kg). A transient increase in residual thrombin activity was measured 12 h after an intravenous (80 U/kg) injection of heparin. Large doses of heparin (80 U/kg IV followed by 160 U/kg SC) given every 12 h produced a progressive prolongation of the APTT. In this group the APTT remained prolonged 48 h after the last treatment.     

Heparin: A Review of its Pharmacology and Therapeutic Use in Horses

Heparin is used clinically in horses to treat hemostatic abnormalities associated with severe gastrointestinal disease, septicemia, and endotoxemia. The primary anticoagulant effect of heparin is through the suppression of thrombin-dependent amplification of the coagulation cascade, and inhibition of thrombin-mediated conversion of fibrinogen to fibrin. Heparin may be of benefit in preventing the complications associated with hypercoagulable states such as jugular vein thrombosis, laminitis, and organ failure. Heparin may also be beneficial in the prevention of intraabdominal adhesions after gastrointestinal surgery, and in amelioration of hemodynamic abnormalities associated with endotoxic shock. Because a sequential rise in serumheparin concentration occurs during a uniform dosage regimen, a decreasing dosage regimen is recommended. The initial dose recommended is 150 U heparin/kg body weight subcutaneously, followed by 125 U heparin/kg body weight subcutaneously, every 12 hours for six doses. The dose should be decreased to 100 U heparin/kg body weight subcutaneously, every 12 hours, after the seventh dose. Anemia, hemorrhage, thrombocytopenia, and painful swelling at injection sites are complications of heparin administration in horses.     

Pharmacokinetics and pharmacodynamics of a therapeutic dose of unfractionated heparin (200 U/kg) administered subcutaneously or intravenously to healthy dogs

BACKGROUND: Heparin treatment has been recommended for dogs in hypercoagulable states such as disseminated intravascular coagulation, however, potential benefits have to be balanced against the bleeding risk if overdosage occurs. A better understanding of the pharmacology of heparin and tests to monitor heparin therapy in dogs may help prevent therapeutic hazards. OBJECTIVES: The purpose of this study was to evaluate the effects of 200 U/kg of sodium unfractionated heparin (UFH) on coagulation times in dogs after intravenous (IV) and subcutaneous (SC) administration and to compare these effects with plasma heparin concentrations assessed by its antifactor Xa (aXa) activity. METHODS: 200 U/kg of UFH were administered IV and SC to 5 healthy adult Beagle dogs with a washout period of at least 3 days. Activated partial thromboplastin time (APTT), prothrombin time (PT), and plasma aXa activity were determined in serial blood samples. RESULTS: After IV injection, PT remained unchanged except for a slight increase in 1 dog; APTT was not measurable (>60 seconds) for 45-90 minutes, and then decreased gradually to baseline values between 150 and 240 minutes. High plasma heparin concentrations were observed (maximal concentration = 4.64 +/-1.4 aXa U/mL) and decreased according to a slightly concave-convex pattern on a semilogarithmic curve, but returned to baseline slightly more slowly (t240-t300 minutes) than did APTT. After SC administration, APTT was moderately prolonged (by a ratio of 1.55 +/-0.28 APTT t0, range 1.35-2.01) between 1 and 4 hours after administration. Plasma aXa activity reached a maximum of 0.56 +/-0.20 aXa U/mL (range 0.42-0.9 U/mL) after 132 +/-26.8 minutes; this lasted for 102 +/-26.8 minutes. Prolongation of APTTs of 120-160% corresponded to plasma heparin concentrations of 0.3-0.7 aXa U/mL. CONCLUSIONS: As in humans, the pharmacokinetics of UFH in dogs was nonlinear. Administration of 200 U/kg of UFH SC in healthy dogs resulted in sustained plasma heparin concentrations in accordance with human recommendations for thrombosis treatment or prevention, without excessively increased bleeding risks. In these conditions, APTT can be used as a surrogate to assess plasma heparin concentrations. These findings need to be confirmed in diseased animals.     

Low dose calcium heparin in horses: plasma heparin concentrations, effects on red blood cell mass and on coagulation variables

Low dose calcium heparin was administered subcutaneously at 12 hourly intervals to six healthy horses at an initial dose of 150 iu of heparin/kg bodyweight (bwt) and at a maintenance dose of 120 iu/kg bwt. All injections were given at 0900 and 2100 h. Blood samples for monitoring plasma heparin concentrations were obtained prior to, at 2 hourly intervals for 84 h (treatment period), and at Hours 24, 32, 48 and 96 of the control period. Blood samples for monitoring red blood cell (RBC) mass, plasma antithrombin III activity (AT III), activated partial thromboplastin time (APTT), and thrombin time (TT) were taken at 8 hourly intervals during the treatment period and at all of the Control Period Hours. Mean plasma heparin concentrations increased significantly (P less than 0.01) from 2 h after the first to 32 h after the last (seventh) injection. Mean values corresponding to the desired range of heparin in plasma (0.05 to 0.20 iu/ml) were achieved at 21 h after initiation of heparin treatment and were maintained during the following 81 h. Great individual variations in the sensitivity to heparin among horses, cumulation of heparin in plasma with prolonged administration and a marked circadian periodicity in the disposition of heparin affected actually measured plasma heparin values. A chronodiagram revealed peak values around 1300 h, trough values around 0500 h. The peak-trough difference amounted to about 50 per cent. Increasing plasma heparin concentrations were associated with erratic prolongations of mean APTT and TT values. The AT III curve was not affected significantly.(ABSTRACT TRUNCATED AT 250 WORDS)     

Dose-dependent plasma elimination of subcutaneously administered calcium heparin in horses

Pharmacokinetic parameters for subcutaneous low dose heparin in horses have been determined. Four groups of five and one group of eleven mature, healthy horses of various breeds were given single subcutaneous injections of 60, 80, 100, 125, and 150 units of calcium heparin/kg of body weight (U/kg) in the pectoral region. Jugular blood samples were collected prior to, and at hourly intervals for 12 h after injection. Heparin plasma concentrations were measured using a commercially available amidolytic assay. Peak concentrations 4 h after administration were 0.021 +/- 0.016 (mean +/- SD) units of heparin/ml of plasma (U/ml) after 60 U/kg, 0.035 +/- 0.025 U/ml after 80 U/kg, 0.023 +/- 0.004 U/ml after 100 U/kg, 0.034 +/- 0.019 U/ml after 125 U/kg, and 0.053 +/- 0.019 U/ml after 150 U/kg. Data from groups given 60 and 100 U/kg could not be used for kinetic calculations. Elimination constant (l/h), elimination half-life (h), and elimination time (h) calculated to reach base-line values after 80 U/kg were 0.182 +/- 0.041 l/h, 3.8 +/- 0.9 h, and 9.7 +/- 2.2 h. After 125 U/kg, corresponding values were 0.211 +/- 0.019 l/h, 3.3 +/- 0.3 h, 13.4 +/- 1.2 h, and after 150 U/kg 0.098 +/- 0.015 l/h, 7.1 +/- 1.1 h, and 20.6 +/- 3.2 h. Calculated heparin concentrations 12 h after administration of 80, 125, and 150 U/kg were 0.011 +/- 0.002, 0.010 +/- 0.001, and 0.027 +/- 0.004 U/ml.(ABSTRACT TRUNCATED AT 250 WORDS)     

Survival of 59Fe-labeled erythrocytes in cross-transfused equine blood

Whole blood containing 59Fe-labeled erythrocytes (RBC) and unlabeled serum was transfused from a donor horse on 2 occasions into each of 6 recipient horses. Survival of transfused cells was monitored in the recipients as a function of time after transfusion by measuring RBC radioactivity in the recipients. After the 1st transfusion, RBC concentration of 59Fe remained at 60% to 100% of the transfused dose for 4 days, after which radioactivity values dropped to less than 10% of the dose by 6 days in 3 horses. In the 3 other horses, RBC radioactivity dropped immediately after transfusion, reaching minimal values in approximately 48 hours. After the 2nd transfusion, 1 horse retained 80% of the dose in circulating RBC for 4 days; 2 horses demonstrated a rapid loss of circulating radiolabeled RBC, reaching minimal values in 48 hours; and 2 horses demonstrated minimal radioactivity in the RBC mass even immediately after the transfusion. One horse died of anaphylactic shock during the 2nd transfusion. Erythrocyte compatibility tests, using the direct agglutination test, the antiglobulin test, and the hemolytic test, were not effective in predicting survival of transfused RBC.     

Disseminated Intravascular Coagulation Associated with Colic in 23 Horses (1984–1989)

Disseminated intravascular coagulation (DIC) secondary to colic was diagnosed in 23 horses. Each horse was categorized retrospectively as to the cause of the colic based on surgical and/or necropsy findings: group 1 consisted of 14 horses with compromised intestine that required resection and anastomosis; group 2 consisted of 3 horses with nonstrangulating intestinal displacement and/or impactions; and group 3 consisted of 6 horses with colic associated with enteritis and/or colitis. Horses were considered to be affected with DIC if at least three of five hemostatic parameters were significantly abnormal: decreased antithrombin III (AT III) values, increased level of fibrin degradation products (FDP), thrombocytopenia, prolonged activated partial thromboplastin time, and prolonged prothrombin time. The most consistent hemostatic abnormalities were decreased AT III activity, increased FDP titers, and thrombocytopenia. Clotting times were more variable and did not always correlate with the presence of excessive hemorrhage. Excessive hemorrhage was present during surgery in seven horses and occurred within 1 to 12 hours after surgery in nine other horses. In addition to treatment of the primary disease, 19 horses received treatment for DIC consisting of heparin and/or plasma or fresh whole blood transfusions. Heparin alone was used in 12 horses. Heparin, in addition to fresh whole blood transfusions or fresh plasma, was administered to four horses. Three horses were treated with plasma alone. Four other horses were not treated specifically for the DIC. Eight horses (34%) survived the acute coagulopathy. Although a greater proportion of the surviving horses received heparin therapy (87.5%; 7/8) than did those that died (60%; 9/15), the difference was not statistically significant (P = 0.345).(ABSTRACT TRUNCATED AT 250 WORDS)     

Enhanced biliary bilirubin excretion after heparin-induced erythrocyte mass depletion

The effect of large-dose heparin therapy on erythrocyte mass depletion in ponies was investigated to determine whether stimulation of reticuloendothelial cell activity and catabolic function would be evidenced by enhanced catabolism of heme to bilirubin. Ponies with chronic external biliary fistula were used to examine biliary excretion of bilirubin both before and after heparin loading (107 U/kg, IV, plus 320 U/kg, subcutaneously) and at maintenance dosages of 320 U/kg given (subcutaneously) at 12 and 24 hours after initial loading with heparin. Results indicated that by 48 hours after ponies were first treated with heparin, catabolism of heme increased, resulting in a 35% increase in plasma bilirubin concentration and a 65% enhancement in biliary bilirubin excretion. During this period, both hematocrit and blood hemoglobin concentrations decreased by 35%. After the last heparin treatment at 24 hours after initial heparin loading, all measured variables returned toward base line within 48 hours. These studies indicated that heparin augments phagocytosis of erythrocytes, resulting in enhanced plasma bilirubin concentration and biliary bilirubin excretion.     

Amidolytic heparin activity and values for several hemostatic variables after repeated subcutaneous administration of high doses of a low molecular weight heparin in healthy dogs

OBJECTIVE: To determine effects of SC administration of repeated doses of a low molecular weight heparin (LMWH) in dogs. ANIMALS: 5 healthy dogs. PROCEDURE: Each dog received 6 injections (each injection, 150 U of anti-factor-Xa [anti-FXal/kg of body weight, SC) at 8-hour intervals. Blood samples were collected before and 2 hours after the first, second, third, and sixth injections to measure heparin activity, thrombin time, activated partial thromboplastin time (APTT), antithrombin activity, Hct, and platelet count. RESULTS: Heparin activity varied between 0.36+/-0.10 and 0.77+/-0.08 U of anti-FXa/ml (before and 2 hours after the third injection) and between 0.46+/-0.11 and 0.82+/-0.15 U of anti-FXa/ml (before and 2 hours after the sixth injection). Thrombin time and APTT were influenced only slightly. Platelet count, Hct, and antithrombin activity started to decrease significantly 2 hours after the second LMWH injection. Because of the increased consumption of antithrombin, antithrombin activity continuously decreased from 102.1+/-6.3% before the study to 91.0+/-3.0% at the end of the study. CONCLUSIONS AND CLINICAL RELEVANCE: Heparin plasma activity was only slightly higher than that recommended for LMWH treatment of humans, and none of the dogs had signs of increased bleeding. Thus, administration of heparin in accordance with this dosing regimen can be recommended for use in clinical studies. The screening tests investigated were not suitable for use in monitoring LMWH treatment of dogs. Assays that use chromogenic substrates are necessary to reliably monitor LMWH plasma concentrations in dogs.     

Association of maximum voluntary dietary intake of freeze-dried garlic with Heinz body anemia in horses

OBJECTIVE: To characterize hematologic and clinical consequences of chronic dietary consumption of freeze-dried garlic at maximum voluntary intake in horses. ANIMALS: 4 healthy sex- and age-matched horses. PROCEDURE: An initial garlic dose (0.05 g/kg, twice daily) was fed to 2 horses in a molasses carrier as part of their normal ration and was gradually increased to maximum voluntary intake (0.25 g/kg, twice daily) over 41 days. Dietary supplementation then continued for a total of 71 days. Two control horses were fed molasses with no garlic with their ration. Blood samples were collected weekly and analyzed for hematologic and biochemical changes, including the presence of Heinz bodies. Recovery of affected blood values was followed for 5 weeks after termination of dietary supplementation with garlic. RESULTS: At a daily dose of > 0.2 g/kg, horses fed garlic developed hematologic and biochemical indications of Heinz body anemia, as characterized by increases in Heinz body score (HBS), mean corpuscular volume (MCV), mean corpuscular hemoglobin, platelet count, and serum unconjugated and total bilirubin concentrations and decreases in RBC count, blood hemoglobin concentration, mean corpuscular hemoglobin concentration, and serum haptoglobin concentration. Recovery from anemia was largely complete within 5 weeks after termination of dietary supplementation with garlic. Heinz body score and MCV remained high at the end of the 5-week recovery period. CONCLUSIONS AND CLINICAL RELEVANCE: Horses will voluntarily consume sufficient quantities of garlic to cause Heinz body anemia. The potential for garlic toxicosis exists when horses are chronically fed garlic. Further study is required to determine the safe dietary dose of garlic in horses.     

Effect of oral administration of unfractionated heparin (UFH) on coagulation parameters in plasma and levels of urine and fecal heparin in dogs

The effects of heparin administration, by the oral route, were evaluated in dogs. In single and multiple dose studies (single 7.5 mg/kg, multiple 3 × 7.5 mg/kg per 48 h), plasma, urine, and fecal samples were collected at various times up to 120 h after oral administration of unfractionated heparin. Changes in plasma and urine anti-Xa activity, plasma and urine anti-IIa activity, plasma activated partial thromboplastin time (APTT) and antithrombin (ATIII), and chemical heparin in urine and feces were examined with time. There was support for heparin absorption, with significant differences in APTT, heparin in plasma as determined by anti-Xa activity (Heptest) in the single dose study and plasma anti-Xa activity, anti-IIa activity and ATIII; and chemical heparin in urine in the multiple dose study. No clinical evidence of bleeding was detected in any dog during the studies. Oral heparin therapy may be applicable for thromboembolic disease in animals. Further studies are warranted to determine the effects of oral heparin at the endothelial level in the dog.     

Heparin-induced agglutination of erythrocytes in horses

Heparin was administered subcutaneously 2 times a day for 4 days to 5 horses. An additional group of 5 horses was used as time-matched controls. Significant decreases in PCV, erythrocyte count, and hemoglobin concentration were observed during heparin therapy. The mean corpuscular volume (MCV) of the heparin-treated horses increased to a peak value of 66.1 fl on the last day of treatment. Erythrocyte creatine concentration and glucose 6-phosphate dehydrogenase activity increased moderately during the treatment. These data indicated that the rapid, profound increase in MCV during heparin therapy was not primarily a result of release of large immature erythrocytes from the bone marrow. A second experiment was subsequently performed, using 3 horses. These horses were given heparin 2 times a day, as was done in the first experiment. Saline wet mounts of erythrocyte suspensions were examined once a day for the presence of agglutination. Cell suspensions were examined with or without exposure to a dilute trypsin solution, and erythrocyte counts were done on each suspension, using an electronic cell counter. Agglutination of erythrocytes was evident on the first day of treatment and became more pronounced as treatment progressed. Exposure to trypsin solution reversed the agglutination. The apparent erythrocyte count decreased and MCV increased sharply in the samples processed normally, but there was little change in those suspensions exposed to trypsin.(ABSTRACT TRUNCATED AT 250 WORDS)     

Plasma heparin values and hemostasis in equids after subcutaneous administration of low-dose calcium heparin

Different doses of heparin were given to equids SC to establish 0.05 to 0.20 U of heparin/ml of plasma. Plasma heparin values and antithrombin III activities were assayed, using chromogenic substrate methods. Activated partial thromboplastin and thrombin times were determined, using conventional coagulation assays. Tests were run every hour (or every 2 hours for antithrombin III) for 12 hours from 5 groups of 5 equids each after single injection of 40, 60, 80, 100, or 125 U of calcium heparin/kg of body weight and from 11 equids after injection of 150 U of calcium heparin/kg. The smaller dose (40 U/kg) did not or only insufficiently increase plasma heparin values. After 150 U of heparin/kg, plasma heparin concentrations were increased for 11 hours and were significantly (P = 0.05) increased between postadministration hours 2 and 7. The desired range beyond 0.05 U of heparin/ml was achieved between postadministration hours 2 and 6. Antithrombin III, activated partial thromboplastin time, and thrombin time were not significantly affected by any heparin dose. In cumulative studies, 2 equids were given 150 U of heparin/kg 7 times at 12-hour intervals. After the 3rd injection, a mean plasma concentration of 0.20 U of heparin/ml was achieved; after the 7th injection, the mean concentration was 0.22 U of heparin/ml. Four equids were given 150 U of heparin/kg initially, followed by 125 U of heparin/kg 6 times at 12-hour intervals. After the 3rd injection, a maximal plasma heparin concentration of 0.12 U of heparin/ml was achieved; after the 7th injection, the mean concentration was 0.18 U of heparin/ml. Repeated SC heparin injections caused moderate swelling at the injection sites.(ABSTRACT TRUNCATED AT 250 WORDS)     

Evaluation of the interaction of mu and kappa opioid agonists on locomotor behavior in the horse.

This study was designed to determine the interactive effects of mu and kappa opioid agonists on locomotor behavior in the horse. Three doses of a mu agonist, fentanyl (5, 10, 20 micrograms/kg) and a kappa agonist U50,488H (30, 60, 120 micrograms/kg) were administered in a random order to six horses. Locomotor activity was measured using a two minute footstep count. Each dose of U50,488H was then combined with 20 micrograms/kg of fentanyl to determine the interactive effects of the drugs on locomotor activity. A significant increase in locomotor activity was seen with 20 micrograms/kg of fentanyl and all the drug combinations. The combination of U50,488H with fentanyl resulted in an earlier onset of locomotor activity. At the highest doses of the combination (U50,488H 120 micrograms/kg, fentanyl 20 micrograms/kg), the duration of locomotor activity was significantly increased when compared to the other doses. We conclude that locomotor activity is maintained or enhanced in horses when a receptor specific kappa agonist is combined with a mu receptor agonist.     

Effects of heparin treatment on colonic torsion-associated hemodynamic and plasma eicosanoid changes in anesthetized ponies

Large colon torsion frequently is a fatal condition in horses. The purpose of the study reported here was to determine systemic arterial pressure, plasma eicosanoid concentrations, colonic blood flow, vascular resistance, tissue pH, and morphologic features associated with large colon torsion and detorsion, and to evaluate the effects of sodium heparin (80 IU/kg of body weight, IV) treatment on these values. Values were determined in 20 anesthetized ponies that were randomly assigned into 4 equal groups: control; control/heparin; torsion; torsion/heparin. Torsions were created by a 720 degrees rotation of the cecum and colon around their long axes at the sternal and diaphragmatic flexures. After 1 hour of torsion, the torsion was corrected and the colon was allowed to reperfuse for 1 hour. Heparin was administered 30 minutes into the experiment. Parametric data were analyzed (P less than or equal to 0.05), using split-plot analysis of variance, with differences between means evaluated with a modified Bonferroni t test; histopathologic data were analyzed (P less than or equal to 0.05) with a Kruskal-Wallis one-way analysis of variance by ranks. Heparin prevented colonic detorsion-induced hypotension and increases in vascular resistance and thromboxane concentration, and it significantly increased colonic blood flow for 40 minutes during reperfusion. Heparin did not alter prostacyclin concentration or the histologic appearance of the large colon.     

Critical tests and safety studies on trichlorfon as an antiparasitic agent in the horse.

Three series of critical tests were completed on a combined total of 46 horses to determine the efficacy of single doses of trichlorfon against bots, ascarids, pinworms, and large strongyles. Different formulations of trichlorfon were administered by tubing intragastrically, mixing with the daily grain ration, injecting intramuscularly, or pouring on the back at dose rates between 20 and 100 mg/kg. Administration by feeding tended to be more efficacious for removal of bots and less toxic to the horese than administration by stomach tube. In many of the tests, trichlorfon was given in the grain ration at the dose rate of 40 mg/kg of body weight, and the aggregate average removals of 2nd and 3rd instars of Gastrophilus intestinalis and Gasterophilus nasalis in the 3 series of tests were between 97 and 100%. Removal of Parascaris equorum was equally efficacious with both the intubation and the grain feeding methods of dosing, and at the dose rate of 40 mg/kg, the aggregate averages were 99 and 100% in the 3 series. Removal of Oxyuris equi was variable--aggregate averages were between 11 (1 infected horse in the initial series) and 96 (5 infected horses in the 3rd series) to 100% (7 infected horses in the 2nd series). Large strongyles, Strongylus vulgaris and Strongylus edentatus were almost completely refractory to the 40-mg/kg dose rate of trichlorfon. Dose rates of 40 mg/kg and less were generally well tolerated by the critical test horses. Higher dose rates (60 and 80 mg/kg) administered by stomach tube induced moderately severe to severe colic and diarrhea, whereas a dose of 80 mg/kg given in the feed resulted in only a transient softening of the feces. Likewise, 5 consecutive doses, 1 week between doses, of a bolus formulation given at the rate of 80 mg/kg to 4 horses were well tolerated. Clinical trials involving a total of 2,294 treatments of trichlorfon at dose rate of 35 to 40 mg/kg in pregnant and nonpregnant mares, stallions, suckling and weanling foals, yearlings, and horses in training on 38 farms in central Kentucky did not cause notable adverse clinical effects.     

Prekallikrein deficiency in a family of miniature horses

Two sibling miniature horses, a male and a female, had a normal 1-stage prothrombin time and a prolonged activated-partial thromboplastin time (APTT). The addition of as little as 5% of a normal equine plasma pool to the plasma samples of both horses shortened their prolonged APTT to within normal limits. Coagulation factor analysis revealed deficiencies in factor XII (12 and 13 U/dl, control population 77 to 128 U/dl), when determined with a feline factor XII-deficient plasma substrate, but normal concentrations (119 and 96 U/dl) when a human factor XII-deficient plasma substrate was used. Deficiencies of another factor, prekallikrein, were detected with a human prekallikrein-deficient plasma substrate (16 and 6 U/dl, control population 70 to 173 U/dl). Other intrinsic coagulation factors were present in normal concentrations. The APTT was measured with plasma from the 2 horses after various incubation periods (1 to 15 minutes) with a contact activator before the addition of Ca ions. With incubation times of greater than or equal to 10 minutes, the APTT of both horses were essentially the same as that of the normal equine plasma pool. Several family members of the 2 prekallikrein-deficient miniature horses appeared to be heterozygous carriers of the prekallikrein deficiency.     

Antagonism of detomidine sedation with atipamezole in horses

The reversal of detomidine-induced sedation with iv atipamezole was studied in 6 horses. All horses were injected iv with 10 μg and 20 μg/kg bwt detomidine and 15 min later this was followed by 6-, 8- and 10-fold doses of iv atipamezole. Atipamezole caused a quick arousal in all horses with minor side effects. Bradycardia, rhythm disturbances and head ptosis caused by detomidine were not abolished completely at the end of the 15 min observation period, even with the highest atipamezole doses. All horses remained slightly sedated but without ataxia. There were no significant differences in head height, heart rate and sedation score between the different doses of atipamezole for either dose of detomidine. According to the degree of sedation, doses of 100 μg to 160 μg/kg bwt atipamezole are adequate to antagonise detomidine-induced sedation in the horse.     

Chronic lead poisoning in horses

Lead acetate was fed to 4 groups of 2 horses each to study chronic lead intoxication. A 5th group of 3 horses was maintained as controls. The leas was fed in capsules, with the minimum dosage of 6.25 mg/kg/day of lead as lead acetate (group I). The dose was increased from group I through group IV in an approximate geometric series, with each group being given about 125% of the dose given the previous group. These doses were given for 105 days, a period designated as phase 1. Since clinical signs were not observed after 105 days, the doses were increased and fed for an additional 190 days (days 106 to 295). This period was designated phase 2. The smallest daily dose in phase 2 was set at about 125% of the largest daily dose in phase 1. The doses in each group was increased by about 125% of that of the previous group, as was done in phase 1. Seven horses died or were euthanatized after 18 to 190 days of phase 2 (123 to 295 days after the 1st dose). One horse in group I did not develop any clinical signs of intoxication. Dose-related responses were unnoticed with doses larger than 15.3 mg/kg/day. All horses given lead had increased blood lead and serum iron concentrations. During phase 2, the hematocrit (erythrocyte volume) and hemoglobin contents were depressed. The lead concentration in kidney, liver, spleen, pancreas, brain, bone, and heart was increased in the treated horses. The dose level required to produce lead intoxication was greater than that reported for cattle and that estimated in epizootiologic studies of horses.     

The effects of dose and diet on the pharmacokinetics of omeprazole in the horse

This study aimed to investigate the effect of diet and dose on the pharmacokinetics of omeprazole in the horse. Six horses received two doses (1 and 4 mg/kg) of omeprazole orally once daily for 5 days. Each dose was evaluated during feeding either a high‐grain/low‐fibre (HG/LF) diet or an ad libitum hay (HAY) diet in a four‐way crossover design. Plasma samples were collected for pharmacokinetic analysis on days 1 and 5. Plasma omeprazole concentrations were determined by ultra‐high pressure liquid chromatography–mass spectrometry. In horses being fed the HG/LF diet, on day 1, the area under the curve (AUC) and maximal plasma concentration (C_max) were higher on the 4 mg/kg dose than on the 1 mg/kg dose. The AUC was higher on day 5 compared to day 1 with the 4 mg/kg dose on the HG/LF diet. On days 1 and 5, the AUC and C_max were higher in horses being fed the HG/LF diet and receiving the 4 mg/kg dose than in horses being fed the HAY diet and receiving the 1 mg/kg dose. These findings suggest that both dose and diet may affect pharmacokinetic variables of omeprazole in the horse.