Decay-Accelerating Factor Mitigates Controlled Hemorrhage-Instigated Intestinal and Lung Tissue Damage and Hyperkalemia in Swine
Abstract
Background Activation of complement system has been associated with tissue injury after hemorrhage and resuscitation in rats and swine. This study investigated whether administration of human recombinant decay-accelerating factor (DAF; a complement regulatory protein that inhibits classical and alternative pathways) reduces tissue damage in a porcine model of hemorrhagic shock. Methods Male Yorkshire swine assigned to four groups were subjected to controlled, isobaric hemorrhage over 15 minutes to a target mean arterial pressure of 35 mmHg. Hypotension was maintained for 20 minutes followed by a bolus intravenous injection of DAF or vehicle then animals were observed for 200 minutes. Blood chemistry and physiological parameters were recorded. Tissue samples from lung and small intestine were subjected to histopathological evaluation and detection of tissue deposition of complement proteins by immunohistochemistry and Western blot analyses. Results Administration of DAF significantly reduced intestinal and lung tissue damage in a dose-dependent manner (5, 25, and 50 g/kg). In addition, DAF treatment improved hemorrhageinduced hyperkalemia. The protective effects of DAF appear to be related to its ability to reduce tissue complement activation and deposition on affected tissues. Conclusions DAF treatment decreased tissue complement activation and deposition in hemorrhaged animals and attenuated tissue damage at 200 minutes post treatment. The observed beneficial effects of DAF treatment on tissue injury after 20 minutes of severe hypotension presents an attractive model of small volume resuscitation, particularly in situations with a restrictive medical logistical footprint such as far-forward access to first responders in the battlefield or in remote rural or mountainous environments.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2011
- Accession Number
- ADA618812
Entities
People
- Chantal Moratz
- George C. Tsokos
- Jurandir J. Dalle Lucca
- Michael Falabella
- Milomir Simovic
- Yansong Li
Organizations
- United States Army Institute of Surgical Research