Relationship between endothelin and organ dysfunction in SIRS

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-1levels gradually decreased in survivor，whereas elevated ET-1levels 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 shock modelLPS(250 ng/kg/min for 2hr)induced hypotension，metabolic acidosis，hypoxemia，and renal dysfunction in anesthetized dogs.Plasma ET-1levels increased and positively correlated with MAP，MPAP，PCWP，and CV‘P in dogs with endotoxic shock.Pretreatment of nonselective ETⅡD2AⅡD2/ETⅡD2 receptor antagonist，TAK-044(5 mg/kg)，prevented LPS-induced metabolic acidosis，hypoxemia，and renal dysfunction。Therefore，TAK-044is 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 I D 22 ii D 2 I and lactic acidosis.These findings suggest that ET-1plays a compensatory role against vasodilation during endotoxic shock，but excessive ET-1may 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.