scholarly journals Minimizing Ischemia Reperfusion Injury in Xenotransplantation

2021 ◽  
Vol 12 ◽  
Author(s):  
Parth M. Patel ◽  
Margaret R. Connolly ◽  
Taylor M. Coe ◽  
Anthony Calhoun ◽  
Franziska Pollok ◽  
...  
Keyword(s):  
Heart Transplantation ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Primary Graft Dysfunction ◽  
Graft Dysfunction ◽  
Associated Injury ◽  
Genetic Modifications ◽  
Injury Mechanisms ◽  
Human Primate

The recent dramatic advances in preventing “initial xenograft dysfunction” in pig-to-non-human primate heart transplantation achieved by minimizing ischemia suggests that ischemia reperfusion injury (IRI) plays an important role in cardiac xenotransplantation. Here we review the molecular, cellular, and immune mechanisms that characterize IRI and associated “primary graft dysfunction” in allotransplantation and consider how they correspond with “xeno-associated” injury mechanisms. Based on this analysis, we describe potential genetic modifications as well as novel technical strategies that may minimize IRI for heart and other organ xenografts and which could facilitate safe and effective clinical xenotransplantation.

scholarly journals Biomarkers of Cellular Apoptosis and Necrosis in Donor Myocardium Are Not Predictive of Primary Graft Dysfunction

2016 ◽  
pp. 251-257 ◽  
Author(s):  
O. SZARSZOI ◽  
J. BESIK ◽  
M. SMETANA ◽  
J. MALY ◽  
M. URBAN ◽  
...  
Keyword(s):  
Cell Death ◽  
Prospective Study ◽  
Reperfusion Injury ◽  
Caspase 3 ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Transplant Recipients ◽  
Primary Graft Dysfunction ◽  
Graft Dysfunction ◽  
Apoptosis Markers

Primary graft dysfunction (PGD) is a life-threatening complication among heart transplant recipients and a major cause of early mortality. Although the pathogenesis of PGD is still unclear, ischemia/reperfusion injury has been identified as a predominant factor. Both necrosis and apoptosis contribute to the loss of cardiomyocytes during ischemia/reperfusion injury, and this loss of cells can ultimately lead to PGD. The aim of our prospective study was to find out whether cell death, necrosis and apoptosis markers present in the donor myocardium can predict PGD. The prospective study involved 64 consecutive patients who underwent orthotopic heart transplantation at our institute between September 2010 and January 2013. High-sensitive cardiac troponin T (hs-cTnT) as a marker of minor myocardial necrosis was detected from arterial blood samples before the donor’s pericardium was opened. Apoptosis (caspase-3, active + pro-caspase-3, bcl-2, TUNEL) was assessed from bioptic samples taken from the right ventricle prior graft harvesting. In our study, 14 % of transplant recipients developed PGD classified according to the standardized definition proposed by the ISHLT Working Group. We did not find differences between the groups in regard to hs-cTnT serum levels. The mean hs-cTnT value for the PGD group was 57.4±22.9 ng/l, compared to 68.4±10.8 ng/l in the group without PGD. The presence and severity of apoptosis in grafted hearts did not differ between grafts without PGD and hearts that subsequently developed PGD. In conclusion, our findings did not demonstrate any association between measured myocardial cell death, necrosis or apoptosis markers in donor myocardium and PGD in allograft recipients. More detailed investigations of cell death signaling pathways in transplanted hearts are required.

Phosphodiesterase-5-inhibition reduces ischemia/reperfusion injury after heart transplantation

2009 ◽  
Vol 56 (S 01) ◽  
Author(s):  
S Loganathan ◽  
T Radovits ◽  
K Hirschberg ◽  
S Korkmaz ◽  
E Barnucz ◽  
...  
Keyword(s):  
Heart Transplantation ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Phosphodiesterase 5
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