Facilitating RBC-mediated Nitric Oxide Release and Boosting Antioxidant Capacity during Ex Vivo Heart Perfusions as a Strategy to Improve Oxygen Delivery
Normothermic ex-vivo heart perfusion (nEVHP) at physiologic temperatures can combat
donor heart shortages through increasing the allowable storage duration of donated hearts
(i.e., 12 h vs. the conventional 4 h) while also providing the opportunity to repair hearts that
would normally be unviable for transplant. Cardiac function, however, declines during
prolonged perfusions due to impairment of RBCs within the perfusate causing a concomitant
decline in oxygenation of the cardiac endothelial cells and surrounding myocardium. To
combat this impairment in RBC function, we propose to pre-condition, or rejuvenate the RBCs
before they are introduced into the heart perfusion system. Such rejuvenation strategies are
in fact conventionally used to boost RBC metabolism when red cell concentrates (RCCs)
have been stored in blood banks for an extended period, or when a recipient requires that
oxygenation provided by the transfused RBCs be optimal. However, we have found that it is
possible to improve conventional rejuvenation strategies in such a way that would render the
RBCs more able to tolerate oxidative stressors encountered within the perfusion system. This
project stands to make significant contributions in two key areas: firstly, by implementing this
cutting-edge RBC rejuvenation technique, we expect to greatly enhance the outcomes of ex
vivo heart perfusion. Secondly, given that the vascular conditions in these perfused hearts
mirrors those encountered in certain critically ill patients, we anticipate that implementing this
approach could in some cases lead to improved outcomes.
donor heart shortages through increasing the allowable storage duration of donated hearts
(i.e., 12 h vs. the conventional 4 h) while also providing the opportunity to repair hearts that
would normally be unviable for transplant. Cardiac function, however, declines during
prolonged perfusions due to impairment of RBCs within the perfusate causing a concomitant
decline in oxygenation of the cardiac endothelial cells and surrounding myocardium. To
combat this impairment in RBC function, we propose to pre-condition, or rejuvenate the RBCs
before they are introduced into the heart perfusion system. Such rejuvenation strategies are
in fact conventionally used to boost RBC metabolism when red cell concentrates (RCCs)
have been stored in blood banks for an extended period, or when a recipient requires that
oxygenation provided by the transfused RBCs be optimal. However, we have found that it is
possible to improve conventional rejuvenation strategies in such a way that would render the
RBCs more able to tolerate oxidative stressors encountered within the perfusion system. This
project stands to make significant contributions in two key areas: firstly, by implementing this
cutting-edge RBC rejuvenation technique, we expect to greatly enhance the outcomes of ex
vivo heart perfusion. Secondly, given that the vascular conditions in these perfused hearts
mirrors those encountered in certain critically ill patients, we anticipate that implementing this
approach could in some cases lead to improved outcomes.
Principal Investigator / Supervisor
ACKER, Jason
Co-Investigator(s) / Trainee
FREED, Darren
Institution
University of Alberta
Program
Intramural Research Grant Program
Province
Alberta
Total Amount Awarded
$377,997
Project Start Date
Project End Date