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Project Title:
Hemadsorption To Improve Donor Organ Recovery
Funding Agency:
Health and Service Administration
Total Project Period:
Sep 01, 2003 - Aug 31, 2006
Principal Investigator:
John Kellum, Jr, MD
Co-Investigator(s):
David J Powner, MD,
Project Summary:
While brain-dead organ donors represent the majority of the organ donor pool, it appears that graft survival is independently adversely affected by brain death itself. In addition to disturbances in the hormonal, hemodynamic and metabolic homeostasis, immunological changes have recently been shown to occur after brain death and these changes contribute both to vascular collapse and organ injury. Increased expression of pro-inflammatory cytokines and their receptors have been demonstrated consistently in the organs and in the circulation of brain-dead animals and humans. Furthermore, the increased inflammatory response seen during and immediately after brain death has also been associated with poor allograft function. Thus, we hypothesize that down- regulating this inflammatory response will lead to improved organ function in the donor and thereby increase organ recovery and subsequent allograft function.
While drug therapy has not shown significant attenuation on the entire inflammatory response, we have shown in preliminary studies highly efficient removal of several inflammatory mediators from the blood of experimental animals using a novel hemo-adsorption device. This device is safe in humans with chronic renal failure and increases survival time in animals exposed to lethal endotxemia. Therefore the purpose of this proposal is to determine whether short-term attenuation of the inflammatory response using CytoSorb can reduce pre-explantation organ dysfunction and thereby improve organ recovery.
Our specific goals (with outcome measures) are: 1. to reduce circulating cytokine levels in potential organ donors (IL-6 levels), 2. to improve organ function in those donors (reversal of shock) and, 3. to increase organ recovery per donor (number of organs recovered per donor).
The intervention sites will be UPMC, Pittsburgh, PA and UTHMC, Houston, TX. The length of the project is 3 years. Data collection will include complete clinical and outcome data as well as several laboratory measures of inflammation and organ function. The analysis will be performed by the analysis committee chaired by a biostatistician. |
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