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 ◽  
...  

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.

2020 ◽  
Author(s):  
Pengyu Zhou ◽  
Hao Liu ◽  
Ximao Liu ◽  
Xiao Ling ◽  
Zezhou Xiao ◽  
...  

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 derived from BMSCs (CM-BMSCs) would improve post-transplant graft function. Methods: Normoxic CM and hypoxic CM 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 CM (N-CM), or hypoxic CM (H-CM), and then heterotopically transplanted. Antibody arrays were performed to compare the differences between hypoxic CM and normoxic CM.Results: After heart transplantation, the donor heart preservation with normoxic CM was associated with shorter re-beating time, histopathological scores, and left ventricular systolic diameter, higher ejection fraction, and fractional shortening of transplanted hearts. These protective effects may be associated with the inhibition of apoptosis and inflammation, as reflected by less TUNEL-positive cells and lower levels of serum proinflammatory cytokines (Interleukin-1β, Interleukin-6, tumor necrosis factor-α) and cardiac troponin I in the N-CM 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 CM compared with normoxic CM. Furthermore, compared with vehicle and N-CM groups, the protein levels of PI3K and p‐Akt/Akt ratio in the transplanted hearts significantly increased in the H-CM group. Conclusions: Our results indicate that cardioplegic solution-enriched with hypoxic CM-BMSCs can be a novel and promising preservation solution for donor hearts.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Pengyu Zhou ◽  
Hao Liu ◽  
Ximao Liu ◽  
Xiao Ling ◽  
Zezhou Xiao ◽  
...  

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 the 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.


Author(s):  
S. A. Alsov ◽  
A. V. Fomichev ◽  
D. V. Doronin ◽  
V. A. Shmyrev ◽  
D. E. Osipov ◽  
...  

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.


2008 ◽  
Vol 78 (6) ◽  
pp. 415-421 ◽  
Author(s):  
Burcak Deniz Dedeoglu ◽  
Erman Aytac ◽  
Oner Suzer ◽  
Huriye Balci ◽  
Hafize Uzun ◽  
...  

Author(s):  
Sandro Sponga ◽  
Igor Vendramin ◽  
Uberto Bortolotti ◽  
Ugolino Livi

2019 ◽  
Vol 18 (3) ◽  
pp. 59-67
Author(s):  
S. M. Minasyan ◽  
Ya. I. Poleshenko ◽  
P. Yu. Shubina ◽  
E. S. Protsak ◽  
D. A. Druzhininsky ◽  
...  

This article describes in detail the modified method of heterotopic heart transplantation in rats. The methods of animal anesthesia, surgical features of the removal of a donor heart and its implantation to a recipient rat are described in detail. The advantages and disadvantages of donor heart preservation methods are described, as well as methods for evaluating a donor heart preparation, the quality of preservation and the effectiveness of cardioprotection. Experimental approaches to the study of the effectiveness of cardioplegic and preservative solutions using this technique are proposed. The data of our own pilot study on a comparative analysis of the effectiveness of cardioprotection using preservative solutions using this experimental model are presented.


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