Optimal time for cardiomyocyte transplantation to maximize myocardial function after left ventricular injury.

Abstract

This study was designed to determine the optimal time for cell transplantation after myocardial injury. The left ventricular free wall of adult rat hearts was cryoinjured and the animals were sacrificed at 0, 1, 2, 4, and 8 weeks for histologic studies. Fetal rat cardiomyocytes (transplant) or culture medium (control) were transplanted immediately (n = 8), 2 weeks (n = 8), and 4 weeks (n = 12) after cryoinjury. At 8 weeks, rat heart function, planimetry, and histologic studies were performed. Cryoinjury produced a transmural injury. The inflammatory reaction was greatest during the first week but subsided during the second week after cryoinjury. Scar size expanded (p < 0.01) at 4 and 8 weeks. Cardiomyocytes transplanted immediately after cryoinjury were not found 8 weeks after cryoinjury. Scar size and myocardial function were similar to the control hearts. Cardiomyocytes transplanted at 2 and 4 weeks formed cardiac tissue within the scar, limited (p < 0.01) scar expansion, and had better (p < 0.001) heart function than the control groups. Developed pressure was greater (p < 0.01) in the hearts with transplanted cells at 2 weeks than at 4 weeks. Cardiomyocyte transplantation was most successful after the inflammatory reaction resolved but before scar expansion.