Topic:Heparin
Heparin is an anticoagulant medication used in horses to prevent and treat blood clot formation. It functions by activating antithrombin III, which inhibits thrombin and factor Xa, key components in the blood coagulation cascade. Heparin is commonly administered in equine medicine to manage conditions such as thrombophlebitis, laminitis, and disseminated intravascular coagulation. The dosage and administration of heparin must be carefully monitored to avoid complications such as hemorrhage. This page compiles peer-reviewed research studies and scholarly articles that explore the pharmacokinetics, therapeutic applications, and potential side effects of heparin in equine practice.
Epididymal maturation affects calcium regulation in equine spermatozoa exposed to heparin and glucose. Spermatozoal function is affected by the ability to regulate intracellular calcium concentrations ([Ca2+]i), and may be influenced by epididymal maturation as well as environmental components. Regulation of [Ca2+]i in ejaculated and epididymal stallion spermatozoa was monitored over time in various media. Spermatozoa from each of 5 pony stallions (3 ejaculate samples and 1 caput and cauda sample) were labeled with the fluorescent calcium indicator probe Indo-1 in a calcium-free modified Tyrode's buffer. Fluorescent emissions were monitored by a dual wavelength spectrofluorometer over 5 h. Calc...
In vitro and xenogenous capacitation-like changes of fresh, cooled, and cryopreserved stallion sperm as assessed by a chlortetracycline stain. Like the human female, the mare experiences reproductive tract pathology that may sometimes be circumvented by the use of assisted reproductive technologies (ARTs). One such technology, gamete intrafallopian transfer (GIFT), may be used in mares that exhibit ovulatory, oviductal, or uterine abnormalities that limit the use of common ARTs, such as embryo transfer. Homologous GIFT has been successfully performed in the horse; however, the logistics, costs, and associated risks of surgically transferring gametes to the oviducts of a recipient mare are considerably high. Use of a less costly speci...
The effect of supramaximal exercise on equine platelet function. When blood is collected into sodium citrate in the proportion of 9 parts blood:1 part sodium citrate, the concentration of plasma sodium citrate in the sample will depend on the packed cell volume (PCV) of the blood sample. This difference in plasma sodium citrate concentration secondary to alterations in PCV significantly affects human platelet aggregation responses. Since horses attain a high PCV in response to high-intensity exercise we investigated the effect of differences in sample plasma sodium citrate concentration on equine platelet aggregability. In addition, low molecular weight hep...
Dietary fat supplementation and equine plasma lipid metabolism. Feeding of a fat-rich diet to horses may enhance the flux of fatty acids, in the form of triacylglycerols (TAG), through the circulation into skeletal muscle. This hypothesis was tested indirectly by measuring the concentration of plasma TAG and the activity of lipoprotein lipase (LPL) in post heparin plasma. Six mature horses were fed a high-fat or a control diet according to a crossover design with feeding periods of 6 weeks. The control diet contained 1.5% fat in the dry matter and the high-fat diet 11.8%. The high-fat diet was formulated by adding soybean oil to the control diet at the exp...
Culture and characterization of equine terminal arch endothelial cells and hoof keratinocytes. To develop methods to isolate, culture, and characterize equine hoof endothelial cells (EC) and keratinocytes. Methods: Cells harvested from the forelimbs of 8 horses. Methods: EC were obtained via catheters placed in the palmar digital arteries of the disarticulated lower portion of the forelimbs from 4 horses that had been heparinized prior to euthanasia. Phosphate-buffered saline solution was used to remove and discard RBC from blood vessels, and collagenase was used to loosen and flush EC from the vasculature. Hoof keratinocytes were obtained from 4 recently euthanatized horses by use of d...
Use of reverse transcriptase-polymerase chain reaction (RT-PCR) and dot-blot hybridisation for the detection and identification of African horse sickness virus nucleic acids. A coupled reverse transcriptase-polymerase chain reaction assay (RT-PCR) for the detection of African horse sickness virus (AHSV) dsRNA, has been developed using genome segment 7 as the target template for primers. RNA from isolates of all nine AHSV serotypes were readily detected. The potential inhibitory effects of either ethylene diamine tetra acetic acid (EDTA) or heparin on the RT-PCR were eliminated by washing blood samples before lysis of the red blood cells and storage. There was a close agreement in the sensitivity and the specificity of the RT-PCR and an indirect sandwich ELISA. Conf...
Current concepts in management of abdominal adhesions. Adhesions are an important complication after abdominal surgery in horses and foals, especially after small intestinal resection and anastomosis. Prevention therapies used in horses have included nonsteroidal anti-inflammatory drugs, antibiotics, heparin, dimethyl sulfoxide, carboxymethylcellulose, and meticulous surgical technique; however, the ideal surgical technique and prevention therapy has not been determined. Further, treatment of abdominal adhesions has a poor prognosis, emphasizing the need for improvements in prevention methods.
Muscarinic signaling pathway for calcium release and calcium-activated chloride current in smooth muscle. We investigated the muscarinic activation of Ca(2+)-activated Cl- currents [ICl(Ca)] in voltage-clamped equine tracheal myocytes. The threshold of cytosolic free Ca2+ concentration ([Ca2+]i) required for activation of ICl(Ca) was 202 +/- 22 nM, and full activation of the current occurred at 771 +/- 31 nM. Hexahydro-sila-difenidol (M3 antagonist) inhibited the methacholine-induced phasic [Ca2+]i increase and ICl(Ca) in a concentration-dependent manner, whereas methoctramine (M2 antagonist) only slightly attenuated the [Ca2+]i increase and ICl(Ca) (14.8 and 21.4%, respectively), consistent with ...
Detection of African horse sickness virus in the blood of experimentally infected horses: comparison of virus isolation and a PCR assay. A reverse transcription-polymerase chain reaction (RT-PCR) assay followed by dot-blot hybridisation was used to detect African horse sickness virus (AHSV); the primers employed amplified the S7 gene that encodes the VP7 protein. The RT-PCR assay was compared with virus isolation for detecting AHSV in blood samples form horses experimentally infected with AHSV-4 and AHSV-9. The influence of sample storage and transportation and the effects of two anticoagulants (EDTA and heparin) were also studied. RT-PCR results were obtained within 48 hours as opposed to a minimum of 15 days for virus isolati...
Isolation and characterization of heparin- and phosphorylcholine-binding proteins of boar and stallion seminal plasma. Primary structure of porcine pB1. In the bovine, seminal plasma heparin-binding proteins bind to sperm lipids containing the phosphorylcholine group and mediate the capacitating effects of heparin-like glycosaminoglycans during sperm residence in the female genital tract. We report the characterization of heparin- and phosphorylcholine-binding proteins of stallion and boar seminal plasma. Horse seminal plasma proteins HSP-1 and HSP-2, and boar protein pB1, belong to the same family as the bull heparin- and phosphorylcholine-binding proteins BSP-A1/2, BSP-A3, and BSP-30K. We have determined the amino acid sequence and posttrans...
A comparison of the lipolytic and anticoagulative properties of heparin and pentosan polysulphate in the thoroughbred horse. The aim of the study was to develop a model for the pre-exercise elevation of plasma free fatty acids in the horse, with a view to its future use in investigations of fat metabolism during exercise. A comparison of the lipase releasing and anticoagulative effects of heparin and a related substance pentosan polysulphate was investigated. Furthermore, the ability of heparin and pentosan polysulphate to affect an increase in plasma free fatty acid concentration, when co-administered with-a triglyceride emulsion, was quantified. Doses of 0.39 and 1.3 mg kg-1 body wt of heparin and pentosan polysul...
Adaptation of equine herpesvirus 1 to unnatural host led to mutation of the gC resulting in increased susceptibility of the virus to heparin. Heparin extensively inhibited infection of MDBK cells by equine herpesvirus 1 (EHV-1) strains adapted to bovine cells or hamsters, while the reagent merely reduced infectivity of strains passaged only in equine cells. The gC of two strains adapted to non-equine cells seemed to have higher affinity for heparin, although the reagent bound to both the gC and gB of all strains tested. Amino acid substitutions of the gC of the EHV-1 strains adapted to non-equine cells converged on the hydrophilic regions, amino acid residues 92 to 175, resulting in the glycoprotein becoming more cationic. These res...
The role of ADP in endotoxin-induced equine platelet activation. We have shown previously that endotoxin induces platelet aggregation in equine heparinised whole blood in a platelet-activating factor (PAF; 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine) dependent manner. ADP is an agonist of platelets and is present in platelet dense granules with ATP in high concentrations. An investigation was carried out to establish whether endotoxin-induced platelet activation was associated with release of platelet ATP and ADP. ADP-scavenging enzyme systems significantly inhibited endotoxin-induced aggregation. Plasma levels of adenine nucleotides were measured using ...
In vitro induction of acrosome reactions in stallion spermatozoa by heparin and A23187. The ability of the glycosaminoglycan, heparin, and the calcium ionophore, A23187, to induce acrosome reaction in equine spermatozoa was assessed using semen from 3 warmblood stallions of known high fertility. After collection of semen, the spermatozoa were washed and incubated in vitro with heparin or A23187. Incubation periods were 0, 4, 6 or 8 h with 0, 1, 10 or 100 microg/ml heparin or 0, 10, 30 or 60 min with 0, 0.01, 0.1, 1 or 10 microM A23187, respectively. Acrosome reactions were determined by staining the spermatozoa with naphthol yellow S plus erythrosin B, and sperm viability was ass...
Platelet-activating factor and not thromboxane A2 is an important mediator of endotoxin-induced platelet aggregation in equine heparinised whole blood in vitro. Endotoxin has previously been shown to induce platelet aggregation in equine heparinised whole blood. This study aimed to determine whether platelet-activating factor or products of cyclo-oxygenase metabolism (thromboxane A2 or prostaglandins) were important in mediating the response of platelets to endotoxin. The effects of the following drugs on endotoxin-induced aggregation were investigated: aspirin, flunixin meglumine and carprofen (non-steroidal anti-inflammatory drugs); CV-3988 and WEB2086 (platelet-activating factor receptor antagonists); quinacrine (phospholipase A2 inhibitor). The ef...
Comparison of the effects of low-molecular-weight and unfractioned heparin in horses. Thirty healthy male horses were allotted to 3 groups and treated blindly during 4 days. Group-1 horses received unfractioned calcium heparin (100 IU/kg of body weight, SC, q 12 h). Group-2 horses received a single dose of a low-molecular-weight heparin (50 anti-Xa IU/kg, SC) every morning, and a similar volume of saline solution every evening. Group-3 horses received the vehicle (saline solution), SC, every 12 hours. Citrated and EDTA-anticoagulated blood samples were collected before starting the medication (T-0) and once daily 3 hours after each morning injection (T-3, T-27, T-51, and T-75)....
Digital Starling forces and hemodynamics during early laminitis induced by an aqueous extract of black walnut (Juglans nigra) in horses. Starling forces and hemodynamics in the digits of 5 horses were studied during early laminitis induced by oral administration of an aqueous extract of black walnut (Juglans nigra). The black walnut extract was prepared from heartwood shavings and was administered by nasogastric tube. Heart and respiratory rates, rectal temperature, central venous and arterial pressures, digital pulses, and signs of lameness were monitored. Blood samples were collected for determination of WBC count, hemoglobin concentration, and PCV and for endotoxin and tumor necrosis factor assays. Total WBC count and centra...
Effect of glycosylation on the heparin-binding capability of boar and stallion seminal plasma proteins. Boar and stallion seminal plasmas were fractionated using affinity chromatography on heparin-Sepharose. In both species, among other proteins, the heparin-binding (H+) and non-heparin-binding (H-) fractions each contained glycoforms of either porcine PSP-I or equine HSP-1 and HSP-2. However, porcine H+/PSP-I eluted as a monomeric protein, whereas H-/PSP-I formed a heterodimer with PSP-II, another major seminal plasma protein. On the other hand, the stallion proteins H+/HSP-1 and H+/HSP-2 eluted together as an aggregate of relative molecular mass (M(r)) 90,000, whereas H-/HSP-1 and H-/HSP-2 elu...
Hyperlipidemia, hyperlipemia, and hepatic lipidosis in American miniature horses: 23 cases (1990-1994). The medical records of 23 American Miniature Horses with hyperlipidemia, hyperlipemia, or hepatic lipidosis were reviewed. The most common clinical signs were anorexia and lethargy. The mean duration of clinical signs was 2.4 days. A primary disease was identified in 19 cases. Enterocolitis was the most common primary disease (n = 10). Intentional feed restriction, as part of treatment for colic, resulted in hyperlipemia in 2 horses and hyperlipidemia in 1. Four horses had primary hyperlipemia, 3 of which had signs of hepatoencephalopathy secondary to hepatic lipidosis. Dextrose, heparin, and ...
Amino acid sequence of HSP-1, a major protein of stallion seminal plasma: effect of glycosylation on its heparin- and gelatin-binding capabilities. We report the complete amino acid sequence of HSP-1, a major protein isolated from stallion seminal plasma or acid extracts of ejaculated spermatozoa. The protein consists of 121 amino acids organized in two types of homologous repeats arranged in the pattern AA'BB'. Each of the 13-15-residue A-type repeats contains two O-linked oligosaccharide chains. The B-type repeats span 44-47 amino acids each, are not glycosylated, and have the consensus pattern of the gelatin-binding fibronectin type-II module. This domain also occurs in the major bovine seminal plasma heparin-binding proteins PDC-109 (...
Pharmacokinetics of heparin and its pharmacodynamic effect on plasma lipoprotein lipase activity and coagulation in healthy horses. We evaluated the pharmacokinetics of IV administered sodium heparin and the pharmacodynamic effect of heparin on lipoprotein lipase (LPL) activity. Horses were allotted to 3 groups. Plasma samples were obtained from each horse before and at various times for 6 hours after heparin administration for determination of heparin concentration, LPL activity, and activated partial thromboplastin time (APTT). The disposition of heparin was dose dependent. The area under the plasma heparin concentration vs time curve (AUC) increased more than proportionally with dose, indicating that heparin elimination...
Endotoxin-induced platelet aggregation in heparinised equine whole blood in vitro. Endotoxaemia is a leading cause of death among horses. Thrombocytopenia is a common finding in clinical and experimentally-induced cases of endotoxaemia and can lead to coagulopathies, including disseminated intravascular coagulopathy which is usually fatal. In this study it was shown that endotoxin (3 ng ml-1 to 25 micrograms ml-1) can aggregate equine platelets in heparinised whole blood in vitro. The endotoxin-induced aggregation (EIA) was shown to be dependent on the presence of leucocytes in the blood and did not occur when detoxified endotoxin was used, suggesting that lipid A was necess...
Effect of sample handling on measurement of plasma glucose and blood lactate concentrations in horses before and after exercise. Collection of a satisfactory blood sample requires special procedures to prevent changes in glucose and lactate content after the sample has been obtained. Changes in measured plasma glucose and blood lactate concentrations attributable to anticoagulants and storage procedures, respectively, were examined in blood samples obtained from horses at rest and after exercise. To evaluate the effect of anticoagulants on measured plasma glucose concentration, blood was preserved with either sodium fluoride/potassium oxalate or lithium heparin. Measured plasma glucose concentration in blood obtained at...
GRASP: a novel heparin-binding serum glycoprotein that mediates oligodendrocyte-substratum adhesion. Cell-substratum adhesion plays a crucial part in the cascade of events that control growth or turn on and consummate a differentiation program. We are investigating the molecular basis of oligodendrocyte (OLG) cytodifferentiation, employing pure cultures of OLGs isolated from postmyelination brains. We have shown that such OLGs will regenerate in vitro and reenact the ontogenic development of myelin, but to do so they need a signal. Adherence to a polylysine surface in the presence of 20% horse serum generates such a signal. Among the events that are turned on upon OLG adhesion is the phosphor...
Evidence that halothane anaesthesia induces intracellular translocation of surface coat and Golgi response in equine pulmonary intravascular macrophages. The pulmonary intravascular macrophages (PIMs) of horse contain a unique electron-dense globular surface-coat which is arranged in a linear fashion in conformity with the contours of the cell membrane. The coat is sensitive to heparin treatment and to the digestive effect of lipolytic lipase, suggesting that the coat is predominantly composed of lipoproteins. During the present study, ultrastructural features of PIMs were analysed after exposing horses to halothane inhalation which was chosen as the model agent of lipid-soluble anaesthetic. The surface-coat showed acute sensitivity to halothan...
Effects of heparin, venous strangulation obstruction of the small intestine, and reperfusion of the small intestine on plasma diamine oxidase activity in horses. Diamine oxidase (DAO), an enzyme of small intestinal origin, is released from mucosal storage sites by IV administration of heparin, to yield the plasma postheparin DAO (PHD) curve. The PHD curve is diminished when mucosal surface area is lost, and baseline (without heparin) plasma DAO activity increases when mucosal storage sites are damaged. Plasma DAO activity was measured after 2 doses of heparin were administered IV in healthy, conscious horses. In anesthetized horses, the PHD curve was studied: during sham small intestinal surgery, and during venous strangulation obstruction (VSO) of the...
[Effect of the time of sample collection after exertion and the specimen handling on the lactate content in the blood of horses]. The mean maximal lactate concentration of horses after exercise (Lamax) amounted to 4.5 +/- 2.2 mmol/l for gallop workouts of less than 11 m/s and more than 180 s (n = 35; category A), at more than 11 m/s and less than 180 s duration (n = 17; category B) to 16.3 +/- 4.8 mmol/l and at less than 11 m/s and less than 180 s duration (n = 10; category C) to 4.6 +/- 1.6 mmol/l. Lamax was always measured immediately after exercise following exercise of categories A and C. But for exercise bouts of category B Lamax was measured between the first and the tenth minute after exercise. Following exercise ...
Prevalence and factors associated with development of laminitis in horses with duodenitis/proximal jejunitis: 33 cases (1985-1991). Medical records of 116 horses admitted to the Texas Veterinary Medical Center between Jan 1, 1984 and Dec 31, 1991 with duodenitis/proximal jejunitis (DPJ) were reviewed. The prevalence of laminitis was 28.4% (33/116; 95% confidence interval: 20.2 to 36.6%). The prevalence of DPJ and DPJ-associated laminitis did not appear to vary significantly by year during the study period. Anamnesis, physical examination, clinicopathologic data, and initial treatment recorded at the time of admission were reviewed to determine risk factors associated with development of laminitis associated with DPJ. A tre...
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 g...
Diagnosis of EDTA-dependent pseudothrombocytopenia in a horse. Thrombocytopenia in horses may be idiopathic or secondary to chronic infectious or inflammatory diseases (eg, equine infectious anemia, lymphosarcoma), drug administration, bone marrow depression, myelophthisic disease, or disseminated intravascular coagulation. This report describes EDTA-dependent pseudothrombocytopenia in a horse. Platelet counts for blood containing EDTA were consistently less than reference range, but platelet counts of blood containing heparin were within reference range. When thrombocytopenia is diagnosed in horses without clinical evidence of a bleeding tendency, EDTA-d...