Nafamostat Attenuated the Impairment of Fibrinolysis in Animal Sepsis Model by Suppressing the Increase of Plasminogen Activator Inhibitor Type 1

Abstract

Nafamostat appeared to improve impaired fibrinolysis by suppressing the increase of PAI-1 in plasma, though it did not largely improve clinical parameters.

Effects of Platelet-activating Factor Receptor Antagonist (PAFRA) on Selected Inflammatory and Biochemical Parameters in Lipopolysaccharide-Induced Rat Endotoxemia Model

“…Diaz Padilla et al 32 concluded that rat CRP, similarly to human CRP, could activate autologous comlement, supporting that opsonization of ligands with complement is an important biological function of CRP. As has been previously demonstrated in endotoxaemic animal models by several authors 1,3,33,34 , liver damage and loss of organ integrity, with subsequently the increases in plasma AST and ALT levels occur during endotoxemia as a consequence of LPS damage. We determined that LPS significantly increased hepatic enzymes AST and ALT which are markers of hepatic injury.…”

“…In our work the selected LPS dose (Escherichia Coli, 0.111:B4 1.6 mg/100 g) is a sufficient dose to reach a high concentration of plasma cytokines during endotoxemi in rat 4 . Various researchers have reported the release of LPSinduced proinflammatory cytokines in rat endotoxemic models 3,4,22,23 . Mathiak et al 24 have determined that LPSinduced IL-6 has the highest plasma concentration peak around 4-6 h. Earlier investigation reported that the increase of IL-6 concen-tration correlates with the severity of septic patients 6 .…”

“… İletişim (Correspondence)  +90 332 2232635  rcol@selcuk.edu.tr disseminated intravascular coagulation (DIC), multiple organ failure, and even death 1,2 . Despite the potent antimicrobial treatments, improved levels of monitoring and intensive supportive care in the last decade, sepsis increasingly remains one of major causes of death, and the mortality rate (60%) in animals 3,4 . Sepsis causes a generalized inflammatory reaction including the concurrent activation of several endogenous mediator systems such as immune system, endothelium, and coagulation system 5 .…”

Prognostic factors for fatal outcomes prior to receiving liver transplantation in patients with non‐acetaminophen‐related fulminant hepatic failure

“…Protease inhibitor is reported to be effective for the endotoxin or lipopolysaccharide‐induced pulmonary vascular injury by inhibiting tumor necrosis factor α production by monocytes 32,33 . Furthermore, protease inhibitor is reported to improve impaired fibrolysis by suppressing the lipopolysaccharide‐induced increase of plasminogen activator inhibitor‐1 in plasma 34 . However, glucocorticoid is reported to increase plasminogen activator inhibitor‐1 expression on vascular endothelial cells and may incline the balance of blood coagulation versus fibrinolysis to coagulation; although pulse steroid treatment reduces serum levels of tumor necrosis factor α 35,36 .…”

“…32,33 Furthermore, protease inhibitor is reported to improve impaired fibrolysis by suppressing the lipopolysaccharide-induced increase of plasminogen activator inhibitor-1 in plasma. 34 However, glucocorticoid is reported to increase plasminogen activator inhibitor-1 expression on vascular endothelial cells and may incline the balance of blood coagulation versus fibrinolysis to coagulation; although pulse steroid treatment reduces serum levels of tumor necrosis factor a. 35,36 Protease inhibitor may prevent the progress to multiple organ failure in non-acetaminophen-related fulminant hepatic failure.…”