title: Biomarkers of cellular apoptosis and necrosis in donor myocardium are not predictive of primary graft dysfunction.
abstract: 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.
authors.affiliation: Department of Cardiovascular Surgery, Institute for Clinical and Experimental Medicine, Prague, Czech Republic. onsz@medicon.cz.
authors.forename: O
authors.initials: O
authors.lastname: Szarszoi
authors.forename: J
authors.initials: J
authors.lastname: Besik
authors.forename: M
authors.initials: M
authors.lastname: Smetana
authors.forename: J
authors.initials: J
authors.lastname: Maly
authors.forename: M
authors.initials: M
authors.lastname: Urban
authors.forename: J
authors.initials: J
authors.lastname: Maluskova
authors.forename: A
authors.initials: A
authors.lastname: Lodererova
authors.forename: L
authors.initials: L
authors.lastname: Hoskova
authors.forename: Z
authors.initials: Z
authors.lastname: Tucanova
authors.forename: J
authors.initials: J
authors.lastname: Pirk
authors.forename: I
authors.initials: I
authors.lastname: Netuka
mesh_terms: D000328:Adult; D017209:Apoptosis / Q000502:physiology*; D005260:Female; D016027:Heart Transplantation / Q000009:adverse effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D009336:Necrosis / Q000175:diagnosis / Q000378:metabolism; D011237:Predictive Value of Tests; D055031:Primary Graft Dysfunction / Q000175:diagnosis* / Q000378:metabolism*; D011446:Prospective Studies; D014019:Tissue Donors