Abstract 17722: Recipient Treatment With Donepezil, an Acetylcholinesterase Inhibitor , Abolishes Donor Heart Ischemia/Reperfusion Injury and Chronic Graft Failure Through TNF Inhibition in an Syngenic Rat Model
Introduction: Ischemia/reperfusion injury (IRI) may have deleterious consequences for donor heart. The underlying mechanisms involve inflammation that may culminate in primary or chronic graft failure.
Hypothesis: Donepezil, an acetylcholinesterase inhibitor, can protect the post-transplanted donor heart by inhibiting systemic inflammation of the recipients.
Methods: Here, we report in Lewis to Lewis rat syngenic heart transplantation model that ischemia/reperfusion injury resulted in primary and chronic graft failure that was prevented by recipient treatment with peroral single-dose Donepezil.
Results: Donepezil inhibited the release of cytokines (TNF, IL-1β, IL-6 and IL18), CD11b/18 positive cell infiltration and myocardial apoptosis in the recipient rats one week postoperatively. One month after transplantation, the graft survival rate in Donepezil group was 46.7% than that in SHAM group (P<0.05); the EF value in Donepezil group was 13% higher than that in SHAM group (P<0.05). The cardiac fibrosis grade was 1 grade lower in Donepezil group than that in SHAM group (P<0.05). Methyllycaconitine blocked the actions of Donepezil, suggesting that the donor heart protection effects are α7-nAChRs-dependent.
Conclusions: Our results reveal that recipient treatment with Donepezil protects donor hearts through TNF inhibition and TNF related downstream pathophysiological pathways. These results suggest a novel, clinically feasible strategy to protect donor hearts from IRI.
Author Disclosures: X. Yuan: None. X. Teng: None. J. Hou: None.
- © 2015 by American Heart Association, Inc.