1999 Fiscal Year Final Research Report Summary
Relationship between endothelin and organ dysfunction in SIRS
| Project/Area Number |
09671543
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Anesthesiology/Resuscitation studies
|
|---|
| Research Institution | Tokyo Medical and Dental University |
|---|
Principal Investigator |
MITAKA Chieko Tokyo Medical and Dental University, Postgraduate Research Institute, Assistant professor, 大学院・医歯学総合研究科, 助教授 (20126254)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
TSUNODA Yukio Tokyo Medical and Dental University, Assistant professor, 医学部・付属病院, 助教授 (30092422)
NAGURA Takashi Tokyo Medical and Dental University, Assistant, 医学部・付属病院, 助手 (80192243)
|
|---|
| Project Period (FY) |
1997 – 1999
|
| Keywords | Endotoxic shock / Endothelin / Endothelin receptor antagonist / Hemodynamics / Renal blood flow / Renal function / NO synthase inhibitor / Post operation of abdominal aortic aneurysm |
|---|
| Research Abstract |
1) Clinical study
Endothelin-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 model
LPS (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.
|
Research Products
(8 results)
