Left-ventricular hypertrophy in 18-month-old donor rat hearts was not associated with
graft dysfunction in the early phase of reperfusion after cardiac transplantation-gene
expression profiling
Nemzeti szívprogram(NVKP_16-1–2016-0017) Támogató: NKFIH
(Higher Education Institutional Excellence Program of the Ministry for Innovation
and Technology in Hungary, within the Semmelweis University)
(Therapeutic Development Thematic Programme of the Semmelweis University)
The use of hearts with left-ventricular (LV) hypertrophy (LVH) could offer an opportunity
to extend the donor pool for cardiac transplantation. We assessed the effects of LVH
in 18-month-old spontaneously hypertensive stroke-prone (SHRSP) donor rats and following
transplantation. In donors, cardiac function and structural alterations were assessed.
Then, the hearts were transplanted into young normotensive-rats. We evaluated LV graft
function 1 h after transplantation. The myocardial expression of 92 genes involved
in apoptosis, inflammation, and oxidative-stress was profiled using PCR-array. Compared
to controls, SHRSP-rats developed LVH, had increased LV systolic performance (slope
of the end-diastolic pressure-volume (PV) relationship: 1.6 +/- 0.2 vs 0.8 +/- 0.1mmHg/mu
l, p<0.05) accompanied by diastolic dysfunction [prolonged time constant of LV pressure
decay (Tau: 15.8 +/- 0.6 vs 12.3 +/- 0.5ms) and augmented diastolic stiffness (LV
end-diastolic PV relationship: 0.103 +/- 0.012 vs 0.045 +/- 0.006mmHg/ml), p<0.05].
They presented ECG changes, myocardial fibrosis, and increased nitrotyrosine immunoreactivity
and plasma troponin-T and creatine kinase-CM levels. After transplantation, even though
the graft contractility was better in SHRSP rats compared to controls, the adverse
impact of ischemia/reperfusion-injury on contractility was not altered (E-es ratio
after versus before transplantation: 32% vs 29%, p>0.05). Whereas nitrotyrosine immunoreactivity
was higher, myeloperoxidase-positive cell infiltration was decreased in the SHRSP+transplanted
compared to control+transplanted. Among the tested genes, LVH was associated with
altered expression of 38 genes in donors, while transplantation of these hearts resulted
in the change of four genes. Alterations in 18-month-old donor hearts, as a consequence
of hypertension and LVH, were not associated with graft dysfunction in the early phase
of reperfusion after transplantation.
