The Effects of Hyperglycemia and Endotoxemia on Coagulation Parameters in Healthy Adult Horses

Abstract

Background: Hyperglycemia and endotoxemia have been associated with coagulation abnormalities in horses. Studies in humans suggest greater disturbances in coagulation with hyperglycemia and concurrent endotoxemia.Objectives: To compare coagulation parameters in horses administered with lipopolysaccharide (LPS) with and without concurrent hyperglycemia.Animals: Twelve healthy adult horses. Methods: Hyperglycemia (180-240 mg/dL) was maintained for 6 hours in 6 horses (GLU-LPS) using 140 mg/kg IV bolus of dextrose followed by a 20% dextrose constant rate infusion. A similar volume of saline was administered to an additional 6 horses (SAL-LPS). LPS (20 ng/kg) was administered to each horse. Fibrogen concentration, prothrombin time (PT), activated partial thromboplastin time (aPTT), thrombin antithrombin concentration (TAT), and thromboelastometry were measured at baseline and after 1, 1.5, 2, 2.5, 3, 4, 6, and 22 hours. Repeated measures analysis of variance was used to examine temporal changes.Results: Increases in PT (P = .001) and TAT (P = .027) were observed in the GLU-LPS group. Changes in thromboelastometry parameters including increased clot formation time (In-TEM, P = .006; Ex-TEM, P = .002) and decreased alpha angle (Ex-TEM, P = .04) and maximal clot firmness (Ex-TEM, P = .014) were observed in the SAL-LPS group. Differences between SAL-LPS and GLU-LPS groups were limited to increased maximal clot firmness (Ex-TEM) at 3, 6, and 22 hours (P < .001) in the SAL-LPS group.Conclusions and Clinical Importance: Minor alterations in coagulation parameters identified for each group are most likely not clinically relevant. Observed differences between groups do not suggest that concurrent hyperglycemia and endotoxemia are associated with greater coagulation abnormalities in horses.

Effects of clopidogrel on horses with experimentally induced endotoxemia

“…35,36 Administration of LPS is a well-established method of experimental induction of endotoxemia in horses. 8,10,13,15,17,37 Lipopolysaccharide causes an innate immune response that is primarily mediated by neutrophils, monocytes, and tissue macrophages. 9,[13][14][15][16]24,26 Leukocyte activation is initiated when LPS, bound to accessory proteins such as CD14 and LPS-binding protein, interacts with the transmembrane receptor toll-like receptor-4, resulting in downstream signaling events, translocation of transcription factors to the nucleus, and subsequent increases in protein synthesis.…”

“…[3][4][5][6] Experimental induction of endotoxemia by administration of a low dose of bacterial LPS has been used to evaluate the pathophysiology of sepsis-induced systemic inflammatory response syndrome. [7][8][9][10][11][12][13][14][15] Several groups of investigators 8,13,16,17 determined the upregulation and time course of leukocyte activation and inflammatory cytokine expression in equids that received LPS. Results of clinical studies 18,19 indicate that inflammatory cytokine expression patterns of leukocytes obtained from horses with naturally occurring gastrointestinal tract disease are related to disease severity and outcome.…”

“…Nevertheless, treatment with anti-inflammatory drugs is not highly effective for the management of horses with endotoxemia. Because of increasing recognition of a relationship between inflammation and coagulation, studies 8,10,21,22 have been conducted to determine the effects of LPS on the activation status of platelets and hemostatic proteins. Administration of LPS to humans results in increased generation of thrombin by activation of the coagulation cascade with both tissue factor-dependent and -independent mechanisms.…”

The influence of experimentally-induced endotoxaemia on clinical variables and markers of systemic inflammation in donkeys (Equus asinus)

“…This effect is presumably caused by the synthesis and release of pro-inflammatory substances, which could inhibit the normal gastrointestinal muscular activity, reduce the threshold for painful stimuli, and/or reduce gastrointestinal blood flow. As a consequence of these possible effects of LPS, it may be surmised that endotoxaemia can increase the likelihood that a donkey Some in vivo experiments have been conducted in horses and ponies using physiological amounts of E. coli O55:B5 endotoxin at doses of 20-30 ng/kg (Moore et al 2007;Toth et al 2008;McGovern et al 2013;Watts et al 2014) or 0.1 µg/kg (Rosa et al 2003), which were given via slow i.v. infusion.…”

Moderate glucose supply reduces hemolysis during systemic inflammation

“…Surprisingly, both moderate and excessive glucose supply reduced LPS-induced hemolysis. An indirect effect of glucose as modulator in the inflammation-related activation of coagulation 31 , 39 can be excluded, since neither moderate nor excessive glucose supply affected LPS-induced alterations in clot formation kinetics. Ultimately, the additional administration of low glucose seems to protect the erythrocytes from “starvation”.…”