Application of thrombelastography in liver injury induced by endotoxin in rat.
Liver injury developing in patients with sepsis may lead to an increased risk of mortality. Thrombelastography (TEG) is generally applied to evaluate hemostatic disturbance in patients undergoing liver transplantation or cardiopulmonary bypass. The aim of this study was to investigate the development of liver injury and coagulopathy in a lipopolysaccharide (LPS)-induced animal model and to assess the relationship between TEG variables and liver injury. Male Wistar rats received LPS (30  mg/kg over a 4-h intravenous infusion) to induce experimental liver injury or isotonic saline as a control. Variables of hemodynamics and liver biochemistry were measured during the subsequent 6 h after the start of infusion. TEG variables (R-time, K-time, α-angle and maximal amplitude), thrombin-antithrombin complex and plasminogen activator inhibitor-1 were also measured. After LPS infusion, liver injury [examined by biochemical variables (e.g. alanine aminotransferase, ALT) and histological studies] was developed and inflammatory cytokines (tumor necrosis factor-α and interleukin-6) were raised. At the initial period of LPS infusion, R-time was shortened and α-angle was increased. Thereafter, α-angle and maximal amplitude were decreased progressively, demonstrating that endotoxin induced coagulation disturbances. Furthermore, there were strong positive correlation between K-time and natural log (Ln)(ALT) (r = 0.823, P = 0.001); also, there were strong negative correlations between α-angle and Ln(ALT) (r = -0.762, P = 0.002) as well as maximal amplitude and Ln(ALT) (r = -0.732, P = 0.004) at 6 h after LPS infusion. These results demonstrated that TEG could be a potential tool to evaluate the development of liver injury in endotoxemia.
Department of Pharmacology, Institute of Pharmacology, National Defence Medical Centre, Taipei, Republic of China, Taiwan.
Hsin-Jung
HJ
Tsai
Cheng-Ming
CM
Tsao
Mei-Hui
MH
Liao
Shuk-Man
SM
Ka
Wen-Jinn
WJ
Liaw
Chin-Chen
CC
Wu
D000818:Animals; D000990:Antithrombin III / Q000032:analysis / Q000378:metabolism; D001778:Blood Coagulation Disorders / Q000097:blood / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology; D001794:Blood Pressure / Q000187:drug effects; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood* / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D019446:Endotoxemia / Q000097:blood* / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D006487:Hemostasis; D015850:Interleukin-6 / Q000097:blood; D008070:Lipopolysaccharides / Q000008:administration & dosage; D008297:Male; D010447:Peptide Hydrolases / Q000032:analysis / Q000378:metabolism; D017395:Plasminogen Activator Inhibitor 1 / Q000032:analysis / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013916:Thrombelastography / Q000379:methods*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D015850:Interleukin-6; D008070:Lipopolysaccharides; D017395:Plasminogen Activator Inhibitor 1; D014409:Tumor Necrosis Factor-alpha; C046193:antithrombin III-protease complex; D000990:Antithrombin III; D010447:Peptide Hydrolases