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Exogenous nitric oxide modulates the systemic inflammatory response and improves kidney function after risk-situation
Francisco S Lozano1, José M López-Novoa, José M Rodriguez
1Angiology and Vascular Surgery Service, University Hospital of Salamanca, Spain. marcellobb@bol.com.br
Journal of Vascular Surgery
|July 14, 2005
Summary
Nitric oxide (NO) donors like molsidomine protect kidney function during aortic surgery by reducing inflammation. This study shows NO donors minimize kidney damage in a preclinical model, even with hemorrhage.
Area of Science:
- Nephrology
- Cardiovascular Surgery
- Immunology
Background:
- Renal impairment is a common complication following aortic surgery, particularly when prolonged suprarenal clamping or hemorrhage is involved.
- The systemic inflammatory response plays a significant role in the development of kidney injury after aortic procedures.
Purpose of the Study:
- To evaluate the protective effect of a nitric oxide (NO) donor on renal function in a minipig model of abdominal aortic surgery.
- To investigate whether NO administration modulates the systemic inflammatory response to mitigate kidney damage.
Main Methods:
- Minipigs underwent suprarenal aortic-iliac clamping and bypass, with or without induced hemorrhage.
- Animals received either sham procedure, clamping/bypass, hemorrhage plus clamping/bypass, or these interventions with prophylactic administration of the NO donor molsidomine.
- Kidney function, inflammatory markers (cytokines, MPO), oxidative stress (SOA, SOD), NO production (nitrites), cell adhesion molecules (sICAM-1, sVCAM-1, ICAM-1, VCAM-1), iNOS, and NF-kappaB were assessed.
Main Results:
- Aortic clamping and hemorrhage significantly worsened kidney function and increased systemic and renal inflammation.
- Molsidomine treatment attenuated the inflammatory response, reduced oxidative stress, and normalized kidney function in both clamped and hemorrhage groups.
- NO donor administration improved endogenous NO production, decreased cell adhesion molecule expression, and reduced NF-kappaB activation.
Conclusions:
- Prophylactic administration of the NO donor molsidomine effectively regulates the systemic inflammatory response and minimizes kidney damage in an experimental model of aortic surgery.
- These findings support the potential clinical relevance of NO donors in preventing renal complications associated with abdominal aortic surgery, especially in the context of hypovolemic shock.