Relationship between endothelin and organ dysfunction in SIRS

Clinical studyEndothelin-1 (ET-1) release during operation correlated (r=0.678) with bleedingvolume during operation in patients with abdominal aortic aneurysm. in two patients with rapture ofabdominal aortic aneurysm, elevated plasma ET-1 level gradually decreased in survivor，whereas elevated ET-1 levels remained high in non-survivor. These findings suggest that plasma ET-1levels reflect the degree of surgical stress and vascular injury.2) Study of canine endotoxic shockmodelLPS (250ng /kg/min for 2hr) induced hypotension, metabolic acidosis, hypoxemia，and renal dysfunction in anesthetized dogs. Plasma ET-1 level increased and positively correlated . Plasma ET-1 level increased and positively correlatedwith MAP， MPAP， PCWP，and CV'P in dogs with endotoxic shock. Pretreatment of nonselective ET ET D2A - D2/ET - 2b - D2 receptorantagonist, tk -044 (5mg /kg), prevented LPS-induced metabolic acidosis, hypoxemia，and renal dysfunction. Therefore，tk -044是一个很好的agent to prevent acute renal failure during endotoxic shock. In addition，selective inducible NO synthase inhibitor, L-canavanine (10mg /kg/hr for 5hr)，further increased plasma ET-1 level，which were with decrease in DO D22 D2I and lactic acidosis. These findings suggest thatET-1 plays a compensatory role against vasodilation during endotoxic shock，but excessive ET-1 may decrease organ blood flow and induce organ dysfunction。

1) Clinical studyEndothelin-1 (ET-1) release during operation correlated (r=0.678) with bleeding volume during operation in patients with abdominal aortic aneurysm. In two patients with rapture of abdominal aortic aneurysm, elevated plasma ET-1 levels gradually decreased in survivor, whereas elevated ET-1 levels remained high in non-survivor. These findings suggest that plasma ET-1 levels reflect the degree of surgical stress and vascular injury.2) Study of canine endotoxic shock modelLPS (250 ng/kg/min for 2 hr) induced hypotension, metabolic acidosis, hypoxemia, and renal dysfunction in anesthetized dogs. Plasma ET-1 levels increased and positively correlated with MAP, MPAP, PCWP, and CV'P in dogs with endotoxic shock. Pretreatment of nonselective ETィイD2AィエD2/ETィイD2BィエD2 receptor antagonist, TAK-044 (5 mg/kg), prevented LPS-induced metabolic acidosis, hypoxemia, and renal dysfunction. Therefore, TAK-044 is a useful agent to prevent acute renal failure during endotoxic shock. In addition, selective inducible NO synthase inhibitor, L-canavanine (10 mg/kg/hr for 5 hr), further increased plasma ET-1 levels, which were associated with decrease in DOィイD22ィエD2I and lactic acidosis. These findings suggest that ET-1 plays a compensatory role against vasodilation during endotoxic shock , but excessive ET-1 may decrease organ blood flow and induce organ dysfunction.