Apoptosis and proliferation of cardiomyocytes and interstitial mononuclear cells: association with rejection and macrophage infiltration.

Previous studies have noted that acute rejection episodes (AREs) may lead to loss of cardiomyocytes in transplanted hearts. The aim of this study was twofold; first, to assess the degree of apoptotic cells and to compute the proliferation index of cardiomyocytes and mononuclear interstitial infiltrates in cardiac allografts. Second, we sought to determine whether apoptosis involved in AREs was associated with macrophage infiltration. Among 28 endomyocardial biopsies, 18 showed AREs and the remaining 10 biopsies, nonspecific changes, the control group. All biopsies were immunostained with Ki-67 and CD68 antibodies. Apoptotic cells were counted using the terminal deoxyncleotidyl transferase dUTP nick end labeling method. Apoptotic death of cardiac myocytes and interstitial mononuclear cells was significantly greater in cases of allograft rejection compared with the control group (P < .05). In addition, compared to the control group, ARE cases showed a greater proliferation index of cardiac myocytes and interstitial cells (P < .05). Macrophage infiltration was significantly greater in ARE cases and macrophage infiltration showed a linear association with both apoptosis and proliferation of myocytes and interstitial cells (P < .001). In conclusion, we verified the presence of apoptotic cell death during acute rejection in heart transplants. Apoptotic cell death was significant among interstitial cells but it was less among cardiac myocytes. Macrophage infiltration had a great influence on apoptotic cell death of myocytes and interstitial cells.