Ex vivo donor heart preservation in heart transplantation

2021 ◽  
Author(s):  
Sandro Sponga ◽  
Igor Vendramin ◽  
Uberto Bortolotti ◽  
Ugolino Livi
Keyword(s):  
Heart Transplantation ◽  
Ex Vivo ◽  
Donor Heart ◽  
Heart Preservation

Abstract 403: Leveraging the Zebrafish to Overcome Barriers in Heart Transplantation

2020 ◽  
Vol 127 (Suppl_1) ◽  
Author(s):  
Shannon N Tessier ◽  
Luciana Da Silveira Cavalcante ◽  
Casie A Pendexter ◽  
Stephanie E Cronin ◽  
Reinier J de Vries ◽  
...  
Keyword(s):  
Heart Transplantation ◽  
Ischemia Reperfusion Injury ◽  
Ex Vivo ◽  
Ischemia Reperfusion ◽  
Complex Structure ◽  
Scale Up ◽  
Adult Zebrafish ◽  
Zebrafish Larvae ◽  
Preservation Method ◽  
Heart Preservation

Cardiac transplantation is the only curative therapy for patients with end-stage heart disease; however, there is a severe shortage of viable donor organs. Heart transplantation faces many interwoven challenges, including both biological factors and research limitations. For example, ischemia-reperfusion injury plays a role in early graft dysfunction and is associated with rejection episodes in heart transplantation. Moreover, experimental transplantation relies heavily on animal studies that are laborious and expensive, prohibiting the discovery of novel, bold solutions. We propose that the zebrafish, Danio rerio , would be a valuable tool for the field since it’s amenable to high-throughput screens, captures the complex structure of organs, and offers a suite of tools to monitor the biology of cardiac injury. Here, we develop a new subzero heart preservation method by strategically leveraging animal models from zebrafish to mammalian hearts. Using zebrafish larvae, we screened for agents which preserve hearts at -10°C. As a result of these screens, we identified promising preservative cocktails which restored heartbeat in 82% of larvae immediately post-recovery. Next, we excised adult zebrafish hearts and developed methods to mimic the ex vivo handling practices of hearts destined for transplant using a heart-on-a-plate assay. Using this assay, we carried forward promising agents identified in our initial zebrafish larvae screen to isolated adult zebrafish hearts that were cooled to -10°C and held for up to 24 hours. After rewarming, heart rate was restored and metabolic rate of zebrafish hearts was like time-matched controls (0.213 ± 0.047 and 0.275 ± 0.060, respectively, p = 0.200). Finally, we report our preliminary scale-up efforts whereby rodent hearts are stored for up to 24 hours at -10°C and viability were assessed by the TUNEL assay. The data shows high viability of cardiomyocytes post-preservation, as compared to controls. In summary, we present data to illustrate our efforts in leveraging the zebrafish to aid new discoveries in subzero heart preservation. Similar efforts to model heart transplantation in zebrafish may provide a different vantage point and enable us to make advances faster.

scholarly journals HEART TRANSPLANTATION WITH EXTREMELY EXTENDED COLD ISCHEMIA TIME OF THE DONOR HEART

2018 ◽  
Vol 20 (1) ◽  
pp. 110-113 ◽  
Author(s):  
S. A. Alsov ◽  
A. V. Fomichev ◽  
D. V. Doronin ◽  
V. A. Shmyrev ◽  
D. E. Osipov ◽  
...  
Keyword(s):  
Heart Transplantation ◽  
Cold Ischemia Time ◽  
Donor Heart ◽  
Cold Ischemia ◽  
Main Method ◽  
Ischemia Time ◽  
Heart Preservation ◽  
Successful Transplantation ◽  
Terminal Heart Failure ◽  
Safe Limit

Heart transplantation is the gold standard for the treatment of terminal heart failure. The main method of the donor heart preservation is cold perfusion. The recommended maximum time for cold ischemia of the donor heart is 240 minutes. Exceeding this safe limit increases the risk of postoperative allograft dysfunction and death. However, there are reports positing a possibility to prolong the time of ischemia of the donor heart without a signifi cant risk of complications. The article presents the experience of successful transplantation of the donor heart with the cold ischemia time was 440 minutes.

scholarly journals Ex Vivo Cryoablation of Wolff-Parkinson-White in a Donor Heart Prior to Pediatric Heart Transplantation

2011 ◽  
Vol 11 (9) ◽  
pp. 1986-1988
Author(s):  
S. R. Ceresnak ◽  
D. T. Hsu ◽  
J. M. Lamour ◽  
S. Weinstein ◽  
R. H. Pass
Keyword(s):  
Heart Transplantation ◽  
Ex Vivo ◽  
Donor Heart ◽  
Pediatric Heart Transplantation

scholarly journals Donor heart preservation with hypoxic conditioned medium derived from bone marrow mesenchymal stem cell improves cardiac function in a heart transplantation model

2020 ◽  
Author(s):  
Pengyu Zhou ◽  
Hao Liu ◽  
Ximao Liu ◽  
Xiao Ling ◽  
Zezhou Xiao ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Heart Transplantation ◽  
Conditioned Medium ◽  
Hypoxic Preconditioning ◽  
Vehicle Group ◽  
Donor Heart ◽  
Cardioplegic Solution ◽  
Heart Preservation ◽  
Antibody Arrays ◽  
Transplanted Hearts

Abstract Background: In heart transplantation, donor hearts inevitably suffer from ischemia/reperfusion (I/R) injury, which leads to primary graft dysfunction and affects patients’ survival rate. Bone marrow mesenchymal stem cells (BMSCs) have been reported to attenuate myocardial I/R injury via their paracrine effects, which can be enhanced by hypoxic preconditioning. We hypothesized that the donor heart preservation with hypoxic conditioned medium (CdM) derived from BMSCs would improve post-transplant graft function. Methods: Normoxic or hypoxic CdM were isolated from rat BMSCs cultured under normoxic (20% O2) or hypoxic (1% O2) condition. Donor hearts were explanted, stored in cardioplegic solution supplemented with either a medium (Vehicle), normoxic CdM (N-CdM), or hypoxic CdM (H-CdM), and then heterotopically transplanted. Antibody arrays were performed to compare the differences between hypoxic and normoxic CdM.Results: After heart transplantation, the donor heart preservation with normoxic CdM was associated with a shorter time to return of spontaneous contraction and left ventricular systolic diameter, lower histopathological scores, higher ejection fraction, and fractional shortening of transplanted hearts. The cardioprotective effects may be associated with the inhibition of apoptosis and inflammation, as reflected by less TUNEL-positive cells and lower levels of plasma proinflammatory cytokines (Interleukin-1β, Interleukin-6, tumor necrosis factor-α) and cardiac troponin I in the N-CdM group compared with the vehicle group. These therapeutic effects can be further enhanced by hypoxic preconditioning. Antibody arrays revealed that nine proteins were significantly increased in hypoxic CdM compared with normoxic CdM. Furthermore, compared with vehicle and N-CdM groups, the protein levels of PI3K and p‐Akt/Akt ratio in the transplanted hearts significantly increased in the H-CdM group. However, no significant difference was found in the phosphorylation of Smad2 and Smad3 for the donor hearts among the three groups. Conclusions: Our results indicate that the cardioplegic solution-enriched with hypoxic CdM can be a novel and promising preservation solution for donor hearts.

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