Left-Ventricular Hypertrophy in 18-Month-Old Donor Hearts Was Not Associated with Graft Dysfunction in the Early Phase of Reperfusion after Cardiac Transplantation: Gene Expression Profiling

Objectives: The use of hearts with left-ventricular hypertrophy (LVH) could offer an opportunity to extend the donor pool for heart transplantation. We assessed the effects of LVH in donor hearts following transplantation in a rat model. Furthermore, myocardial gene expression changes in LVH donors and their implication in transplantation were investigated.

Methods: In 18-month-old spontaneously hypertensive stroke-prone (SHRSP) and normotensive Wistar (control) donor rats, cardiac function was assessed by left-ventricular (LV) pressure-volume (PV) analysis. Structural alterations were characterized by echocardiography and histology, and electrical activities by electrocardiography (ECG). Additionally, plasma samples were obtained. Then, hearts were heterotopically transplanted into young Sprague-Dawley rats. We evaluated in vivo LV graft function 1 hour after transplantation via a Millar catheter system at different LV volumes. The myocardial expression of 92 genes involved in apoptosis, inflammation, and oxidative stress was profiled using PCR array.

Results: Compared to controls, SHRSP rats developed LVH (increased LV mass index, cardiomyocyte diameter normalized to body weight, and heart weight-to-body weight ratio); had increased LV systolic performance (slope Ees of the end-diastolic PV relationship: 1.6 ± 0.2 vs. 0.8 ± 0.1 mm Hg/μL, p < 0.05) with diastolic dysfunction (prolonged time constant of LV pressure decay Tau [15.8 ± 0.6 vs. 12.3 ± 0.5 ms] and augmented diastolic stiffness [LV end-diastolic PV relationship: 0.103 ± 0.012 vs. 0.045 ± 0.006 mm Hg/mL], p < 0.05); and presented ECG changes, myocardial fibrosis, and increased 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 (Ees ratio after vs. before transplantation: 32 vs. 29%). Among the tested genes, LVH was associated with altered expression of 38 genes in donor hearts, while transplantation of these hearts resulted in the changes of four additional genes.

Conclusion: Alterations in donor hearts, as a consequence of hypertension and LVH, were not associated with LV graft dysfunction in the early phase of reperfusion after heart transplantation.