Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/48015
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Type: Journal article
Title: Simvastatin plus nitric oxide synthase inhibition modulates remote organ damage following skeletal muscle ischemia-reperfusion injury
Author: Cowled, P.
Khanna, A.
Laws, P.
Field, J.
Fitridge, R.
Citation: Journal of Investigative Surgery, 2008; 21(3):119-126
Publisher: Taylor & Francis Inc
Issue Date: 2008
ISSN: 0894-1939
1521-0553
Statement of
Responsibility: 
P.A. Cowled, A. Khanna, P.E. Laws, J.B.F. Field, R.A. Fitridge
Abstract: Ischemia-reperfusion injury (IRI) to the lower extremities causes both local damage and serious dysfunction to remote organs, including lungs and kidneys. However, effective therapies are not available. This study aims to determine if simvastatin reduced the severity of remote damage following IRI. Methods: Rats were given simvastatin before hind limb IRI. Lung and kidney tissues were assessed for neutrophil infiltration using myeloperoxidase assays and basement membrane damage by quantitative immunohistochemical measurement of collagen IV. The effect of nitric oxide synthase (NOS) inhibition on remote damage after IRI and simvastatin was assessed using the NOS inhibitor, L-NIO. Results: Simvastatin (2 mg/kg) protected kidneys against IRI-induced neutrophil infiltration. Simvastatin also inhibited the IRI-induced activation of MMP-9 in the lungs. However, paradoxically, simvastatin exacerbated IRI-induced neutrophil infiltration into the lungs. IRI induced collagen IV degradation in the lungs but not in the kidneys. The degree of collagen breakdown in the lungs was significantly ameliorated by 2 mg/kg simvastatin. NOS inhibition markedly protected both the lungs and the kidneys against IRI-induced neutrophil infiltration but did not alter collagen IV degradation. Administration of simvastatin to L-Nio-treated animals enhanced the degree of protection against IRI-induced neutrophil infiltration in the kidneys but not in the lungs. Conclusions: Simvastatin protects against remote IRI-induced damage in the lungs and kidneys, suggesting statins may reduce the severity of IRI during major vascular surgery.
Keywords: ischemia-reperfusion injury; neutrophil; skeletal muscle; lung; kidney; statin; nitric oxide
RMID: 0020080885
DOI: 10.1080/08941930802046501
Appears in Collections:Surgery publications

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