Abstract 184: Inhibition of Nitric Oxide Synthase Attenuate Hemorrhage Induced Inflammatory Response and Protect Against Multiple Organ Injury in a Rat Model
Hemorrhagic shock activates inflammatory pathways and results in upregulation of cytokine synthesis. Nitric oxide has been implicated in the pathophysiology of hemorrhagic shock.
Objectives: We have investigated the protective effects of inhibition of inducible nitric oxide synthase (iNOS) using NG - nitro-L-arginine methyl ester (L-NAME) on preventing organ injury in a rat model of hemorrhagic shock and resuscitation.
Methods: Male Sprague Dawley rats (300-350 gm) were assigned to 3 experimental groups (n= 6 per group): 1) Normotensive rats (N), 2) Hemorrhagic shock rats (HS) and 3) Hemorrhagic shock rats treated with L-NAME (HS-L-NAME). Rats were hemorrhaged over 60 min to reach a mean arterial blood pressure of 40 mmHg. Rats were treated with 1 ml of 8 mg/Kg L-NAME intra-arterially after 60 min hemorrhagic shock. Resuscitation was performed in vivo by the reinfusion of the shed blood for 30 min to restore normo-tension. Arterial blood samples were collected from all groups at the end of the experimental period for measurement of tumor necrosis factor α (TNF-α). Biopsy samples were taken for light microscopy. Histological examination of hemorrhagic shocked untreated rats revealed structural damage. Less histological damage was observed in multiple organs in L-NAME- treated rats. L-NAME-treatment decreased the number of inflammatory cells and mitochondrial swollen in myocardial cells. Treatment with L-NAME decreased the inflammatory response to hemorrhagic shock by lowering the levels of TNF-α. L-NAME treatment reduced microscopic damage and injury in multiple organs and reduced the inflammatory response to hemorrhagic shock by inhibiting iNOS in a hemorrhagic shock model in rats.
- © 2013 by American Heart Association, Inc.