Relationship between endothelin and organ dysfunction in SIRS

1） Clinical studyEndothelin-1（ET-1） release during operation related（r=0.678） with abdominal aortic aneurysm的bleeding volume during operation in patients.在两名患者中，有轻微的急性碱性炎症，升高的等离子体ET-1级在幸存者中研究生退化，升高的ET-1级在非幸存者中保持较高。这些发现建议将等离子体ET-1级反映外科压力和血管损伤程度。2）对大麻内毒素休克模型LPS（250纳克/千克/分钟，每2小时）诱导性低血压、代谢酸中毒、高氧病和肾上腺功能失调的研究。等离子体ET-1级增加，与MAP、MPAP、PCWP和CV'P中的狗与内毒素冲击相关。非选择性ET D2 A/ET D2 B/ET D2受体拮抗剂的预防，TAK-044（5 mg/kg），预防LPS诱导代谢酸中毒、低氧emia和renal dysfunction。因此，TAK-044是一个有效的代理，可以防止内毒素冲击下的急性renal失败。在附加的、选择性的、可诱导的NO合成酶抑制剂中，L-canavanine（5小时10毫克/千克/小时），进一步增加等离子体ET-1水平，与D22 I和乳酸中毒中的降解有关。这些发现建议ET-1发挥了对抗性挥发性休克期间的补偿作用，但额外的ET-1可以减少器官血流和诱导器官紊乱。

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.