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With a focus on learning, we employ a range of strategies to support innovation, collaboration across centers, and university-wide discussion and decision-making

 

Ninth Annual Grant Winners 2008-2009

Dean Andres Malave, Ph.D. (HPD-PHR)

Faculty
Bo Kyung Min, Pharm.D. (HPD-PHR)
William Wolowich, Pharm.D. (HPD-PHR)

Title: The Impact of Coenzyme Q10 Level on Acute Rejection in Cardiac Transplantation

Abstract:

Grant Winners 2008-2009

Background/Rationale:
Cardiac transplantation is the only effective treatment for patients with end stage heart failure refractory to conventional medical therapy. Post-transplantation mortality is estimated to be 12% during the first 6 months and subsequently mortality decreased at a linear rate of 3.4% per year even well beyond 15 years post-transplantation.1 There are several factors significantly affecting one year mortality. Early (peri-operative) ischemic injury is not avoidable during procurement and implantation of a donor heart. Intermittent ischemic periods are primary culprit of free radical formation.2 During reperfusion, the subsequent availability of oxygen to tissues that have accumulated anaerobic metabolites leads to the production of harmful oxygen free radicals. The production of free radicals contributes to cell injury by participating in lipid peroxidation, polymerization of mucopolysaccharides, and oxidation of protein sulfhydryl groups.3 The link between ischemia/reperfusion injury and allograft rejection was proposed and established. Ischemia and reperfusion up-regulate the expression of major histocompatibility complex molecules, particularly class II, thus rendering postischemic allograft more immunogenic.4 Reactive radical species can be scavenged both extra- and intracellularly provided antioxidants. Coenzyme Q10 is pivotal in oxidative respiration and effective in free-radical scavenging. It prevents cellular damage during myocardial ischemia and reperfusion.2
Methods:
Adult patients presenting for their first orthotopic cardiac transplantation are eligible for the study participation. Primary endpoint is the difference of acute rejection episodes during 6 month follow-up stratified by coenzyme Q10 level. Data analysis will compare endomyocardial biopsy results with pre-transplantation coenzymeQ10 levels.
Significance:
It is critically important to prevent acute rejection episodes for first 6 months after cardiac transplantation in order to improve sub-acute and long term graft survival. Coenzyme Q10 has demonstrated free radical scavenging effect.2 Free radicals may be the pathophysiologic mechanism of acute cardiac allograft rejection. This is the first study to investigate coenzyme Q10 level on acute graft survival.