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SUMMARY

Using a pump-perfused extracorporeal isolated digital preparation, the effects of a 30-minute infusion of either saline solution (control) or endotoxin on equine digital hemodynamics and microvascular function were determined. Digital blood flow and arterial, venous, and capillary pressures were recorded at 15-minute intervals for 150 minutes. From these data, total vascular resistance and pre- and postcapillary resistances were calculated. Isogravimetric capillary filtration coefficient, vascular compliance, and the osmotic reflection coefficient were determined after the last hemodynamic measurements were taken.

Changes in hemodynamic values of control equine digits were not observed. During the 120 minutes after infusion of endotoxin, digital blood flow decreased 43%, and total vascular resistance increased 89%. Precapillary resistance increased 122%, but postcapillary resistance did not change significantly. Changes in vascular compliance or the capillary filtration coefficient were not observed in response to either treatment. The osmotic reflection coefficient, an index of permeability, did not differ significantly between digits of the endotoxin-treated and control groups. These data indicate that the increase in vascular resistance during endotoxemia may have been attributable to arterial/arteriolar constriction and that neither the permeability nor the surface area of the exchange vasculature within the digit was significantly affected by endotoxin. Although marked alterations in vascular function are seen after administration of endotoxin, these changes do not parallel those documented in association with experimentally induced laminitis.

Free access
in American Journal of Veterinary Research

SUMMARY

In 6 adult horses anesthetized with pentobarbital, the hemodynamic responses of the equine digit to infusion of dopamine were evaluated by use of an isolated extra corporeal pump perfused digital preparation. Digital blood flow was maintained at a constant rate that was independent of systemic hemodynamic changes. Three sequential experiments were performed on each horse. In the first experiment (n = 6), dopamine was infused iv at rates of 1.0, 2.5, and 5.0 μg/kg/min. For the second experiment (n = 5), dopamine (400 μg/ml) was infused into the digital artery at the rates of 0.07, 0.7, and 1.2 ml/min. The third experiment (n = 5) consisted of a 5-minute intra-arterial infusion of phentoalamine followed by the intra-arterial infusion of dopamine while continuing the infusion of phentolamine. Digital venous, arterial, and capillary pressures, total digital vascular resistance, and precapillary to postcapillary resistance ratios were determined in each experiment.

Systemic infusion of dopamine did not induce changes in the hemodynamics of the digital vasculature. Digital arterial infusion of dopamine alone resulted in a dosedependent increase in arterial pressure, total digital vascular resistance, and an increase in the precapillary to postcapillary resistance ratio. Phentolamine attenuated the vasoconstrictive response elicited by intra-arterial infusion of dopamine.

Free access
in American Journal of Veterinary Research

Abstract

Objective—To evaluate effects of black walnut extract (BWE) on equine mononuclear cells and determine whether BWE has direct proinflammatory effects.

Sample—Mononuclear cells separated from blood samples from 8 horses.

Procedures—Aqueous BWE was prepared and processed to eliminate contamination with particulates and microbes. A Limulus amoebocyte lysate assay was used to detect lipopolysaccharide (LPS) contamination in the BWE. Mononuclear cells were incubated in minimal essential medium with or without the addition of 0.6% to 10% (vol/vol) BWE. These mononuclear cells were assessed for viability, activities of caspases 3 and 7, nitric oxide production, procoagulant activity, and tumor necrosis factor-α production. The effect of LPS on cellular responses induced by BWE was assessed by coincubation with 13 U of polymyxin B/mL; mononuclear cells incubated with LPS were used as a reference.

Results—BWE did not cause loss of cell membrane integrity in mononuclear cells but did induce a dose-dependent increase in activities of caspases 3 and 7. Neither BWE nor LPS significantly induced production of nitric oxide. Both BWE and LPS induced comparable amounts of procoagulant activity and tumor necrosis factor-α production; coincubation with polymyxin B reduced the activity for BWE and LPS by 50% and approximately 100%, respectively.

Conclusions and Clinical Relevance—Addition of BWE induced inflammatory activation of equine mononuclear cells, a portion of which was independent of the effects of LPS. Furthermore, BWE and LPS may work in concert to induce systemic inflammatory responses that contribute to the development of acute laminitis in horses.

Full access
in American Journal of Veterinary Research

Abstract

Objective—To determine the effects of induction of capacitative Ca2+ entry on tone in equine laminar arteries and veins.

Sample Population—Laminar arteries and veins from 6 adult mixed-breed horses.

Procedure—Arteries and veins were isolated and mounted on small vessel myographs for the measurement of isometric tension. Capacitative Ca2+ entry was induced by incubating the vessels with the specific Ca2+-ATPase inhibitor thapsigargin (100nM) in a Ca2+- free physiologic salt solution. Capacitative Ca2+ entry–associated contractile responses were determined by the subsequent addition of 2mM Ca2+ to the solution bathing the vessels; in some experiments, either the voltage-gated Ca2+ blocker diltiazem (10µM) or the putative capacitative Ca2+ entry inhibitor trifluoromethylphenylimidazole (300µM) was added to the bathing solution 15 minutes prior to a second 2mM Ca2+ exposure. The Sr2+ permeability of the capacitative Ca2+ entry pathway in laminar vessels was assessed by exposing the vessels to 4mM Sr2+ after induction of capacitative Ca2+ entry with thapsigargin.

Results—Induction of capacitative Ca2+ entry elicited robust contractile responses in laminar veins but did not increase tone in laminar arteries. In laminar veins, capacitative Ca2+ entry–induced contractile responses were unaffected by preincubation with diltiazem, attenuated by trifluoromethylphenylimidazole, and were impermeable to Sr2+.

Conclusions and Clinical Relevance—Results indicated that induction of capacitative Ca2+ entry elicits vasoconstriction in equine laminar veins but not in laminar arteries and should therefore be considered a potential mechanism by which selective venoconstriction occurs in horses during the development of acute laminitis. (Am J Vet Res 2005;66:1877–1880)

Full access
in American Journal of Veterinary Research

Abstract

Objective—To determine the effect of fetal bovine serum (FBS) and heat-inactivated FBS (HI-FBS) on lipopolysaccharide (LPS)- and zymosan-induced procoagulant activity of equine and canine mononuclear cells.

Sample Population—Mononuclear cells from 18 horses and 3 dogs.

Procedures—Cells were incubated with various concentrations of FBS, HI-FBS, LPS, zymosan, polymyxin B, and anti–LPS-binding protein monoclonal antibody or combinations of these constituents. A 1stage recalcification assay was used to determine procoagulant activity.

Results—Addition of FBS to media significantly increased procoagulant activity; equine and canine cells were stimulated by 1% and 10% FBS, respectively. Coincubation of cells with FBS and polymyxin B did not reduce this effect, suggesting that the response was not attributable to LPS contamination. Addition of HI-FBS to media did not stimulate procoagulant activity of equine or canine cells, and the sensitivity of the equine cells to LPS was significantly increased by HI-FBS. This increased LPS sensitivity was reduced 40% with monoclonal antibody directed against human recombinant LPSbinding protein. Increasing concentrations of HIFBS significantly increased LPS- and zymosaninduced procoagulant activity of canine cells.

Conclusion and Clinical Relevance—Procoagulant activity production in equine and canine mononuclear cells was significantly increased by addition of FBS, whereas heat inactivation of FBS eliminated this effect. Heat inactivation did not eliminate the function of serum proteins involved in enhancement of LPSand zymosan-induced procoagulant activity. Results suggest that HI-FBS can be used as a source of serum proteins that increase the sensitivity of mononuclear cells to bacterial and yeast cell wall components.

Full access
in American Journal of Veterinary Research

SUMMARY

Because certain inflammatory processes are dependent on the fatty acid composition of the cellular membrane, dietary manipulations that replace ω-6 fatty acids with ω-3 fatty acids may modify inflammatory responses. We investigated the effect of supplemental dietary linseed oil, containing the ω-3 fatty acid, α-linolenic acid, on in vivo responses of horses to endotoxin. One group of horses (n = 6) was fed a control pelleted ration (0% linseed oil), and another group of horses (n = 6) was fed an 8% linseed oil pelleted ration. After 8 weeks of consuming these rations, all horses were given 0.03 μg of Escherichia coli 055:B5 endotoxin/kg of body weight, infused over 30 minutes. Horses were monitored over 24 hours. Compared with baseline values within each ration group, endotoxin infusion caused significant (P < 0.05) increase in rectal temperature, heart rate, and plasma concentration of thromboxane B2, 6-keto-prostaglandin F, and fibrinogen and significant (P < 0.05) decrease in total WBC count. Compared with baseline values within each ration group, endotoxin infusion failed to cause significant changes in prothrombin, activated partial thromboplastin, thrombin, or whole blood recalcification times, serum concentration of fibrin degradation products, pcv, or plasma total protein concentration. Before and after endotoxin infusion, horses given the linseed oil ration had longer mean whole blood recalcification time and activated partial thromboplastin time than did horses fed the control ration.

Free access
in American Journal of Veterinary Research

SUMMARY

A study was conducted to determine whether dietary supplements with α-linolenic acid altered the ability of equine peritoneal macrophages to produce tumor necrosis factor (tnf) in response to endotoxin. Peritoneal macrophages were harvested from 6 healthy adult horses before and after the horses were fed a nutritionally balanced ration that contained 8% linseed oil as a source of α-linolenic acid. The macrophages were cultured in media containing no additives (control), endotoxin (0.5 to 50 ng/ml), or the calcium ionophore, A23187. Macrophage supernatants were collected after 6 and 24 hours’ incubation and stored at −70 C. Tumor necrosis factor activity was estimated by a modified in vitro cytotoxicity bioassay, using the murine fibrosarcoma cell line, WEHI 164 clone 13. The tnf activity after 6 and 24 hours’ incubation was greater in culture media of macrophages exposed to endotoxin than in media from control macrophages. For macrophages cultured in media that contained endotoxin, neither the concentration of endotoxin nor incubation time had any effect on tnf activity. Endotoxin-induced macrophage production of tnf, as determined by measurement of tnf activity, was significantly less after horses were fed the α-linolenic acid-rich ration for 8 weeks.

Free access
in American Journal of Veterinary Research
in Journal of the American Veterinary Medical Association

Abstract

Objective—To evaluate the effects of a standardized exercise test to exhaustion in horses on leukocyte function ex vivo.

Animals—6 Thoroughbred geldings.

Procedures—Blood samples were obtained from each horse before exercise; at exhaustion (termed failure); and at 2, 6, 24, 48, and 72 hours after exercise to evaluate hematologic changes, rate of leukocyte apoptosis, and leukocyte production of reactive oxygen species (ROS) ex vivo. To assess leukocyte function, leukocyte ROS production in response to stimulation with lipopolysaccharide, peptidoglycan, zymosan, and phorbol myristate acetate was evaluated. Apoptosis was evaluated via assessment of caspase activity in leukocyte lysates.

Results—In response to lipopolysaccharide, production of ROS by leukocytes was significantly increased at 2 hours and remained increased (albeit not significantly) at 6 hours after exercise, compared with the preexercise value. In the absence of any stimulus, leukocyte ROS production was significantly increased at 6 and 24 hours after exercise. In contrast, ROS production in response to phorbol myristate acetate was significantly decreased at 6, 24, and 72 hours after exercise. Leukocyte ROS production induced by zymosan or peptidoglycan was not altered by exercise. Leukocytosis was evident for 24 hours after exercise, and neutrophilia was detected during the first 6 hours. A significant increase in the rate of leukocyte apoptosis was detected at failure and 72 hours after exercise.

Conclusions and Clinical Relevance—Results indicated that strenuous exercise undertaken by horses causes alterations in innate immune system functions, some of which persist for as long as 72 hours after exercise.

Full access
in American Journal of Veterinary Research

Abstract

Objective—To determine the effects of inhibition of Rho-kinase or Src-family protein tyrosine kinases (srcPTK) on agonist-induced contractile responses in equine laminar arteries and veins.

Sample Population—Laminar arteries and veins obtained from 13 adult mixed-breed horses.

Procedures—Laminar vessels were mounted on myographs and exposed to phenylephrine (PE), 5-hydroxytryptamine (5-HT), prostaglandin F (PGF), and endothelin-1 (ET-1) with or without the Rho-kinase inhibitor Y-27632 (10μM), srcPTK inhibitor PP2 (10μM), or a negative control analogue for PP2 (PP3; 10μM).

Results—Responses to PE were reduced by use of Y-27632 in laminar vessels (approx inhibition, 55%). However, Y-27632 reduced responses to 5-HT to a greater degree in veins than in arteries (approx inhibition of 55% and 35%, respectively). The Y-27632 also reduced responses of laminar veins to ET-1 by approximately 40% but had no effect on maximum responses of laminar arteries to ET-1, although a rightward shift in the concentration response curve was evident. Addition of PP2 reduced responses to PE, 5-HT, and PGF in laminar veins by approximately 40%, 60%, and 65%, respectively, compared with responses after the addition of PP3; PP2 had no effect on responses to ET-1. In laminar arteries, PP2 reduced 5-HT–induced contractions by approximately 50% but did not affect responses to PE or ET-1.

Conclusions and Clinical Relevance—Results of the study were consistent with activation of Rho-kinase being important during agonist-induced constriction in laminar vessels, activation of srcPTK being an agonist-dependent event, and more prominent roles for Rhokinase and srcPTK in veins than in arteries.

Full access
in American Journal of Veterinary Research