Transplantation of neonatal cardiomyocytes after permanent coronary artery occlusion increases regional blood flow of infarcted myocardium

Background. – Cellular cardiomyoplasty is a promising approach for rebuilding scar tissue after acute myocardial infarction. However, the angiogenic potential of transplanted immature cardiomyocytes and their effect on regional myocardial blood flow (RMBF) after coronary artery occlusion remain to be evaluated. Methods and results. – Intramyocardial injection of cultured neonatal cardiomyocytes (4 × 106 cells/50-70 μl) into the scar 1 week after permanent coronary occlusion in rats resulted in improved RMBF in the infarct 4 weeks after transplantation (radioactive microspheres, 0.97 ± 0.18 ml/min/g) in comparison to medium-injected hearts (0.61 ± 0.11 ml/min/g, P < 0.047). The macroscopic perfusion defect after in vivo staining with the blue dye 50% Uniperse blue was significantly smaller in the cell transplantation group (1.5 ± 0.3% of the heart) compared to the medium group (3.0 ± 0.6%, P < 0.017). Clusters of engrafted cells within the scar demonstrated a high capillary density (1217 ± 114 perfused (blue) capillaries/mm2); however, in the scar tissue itself capillary density in the cell group (156 ± 62/mm2) did not significantly differ from the medium group (125 ± 10/mm2), suggesting that neo-angiogenesis was confined to regions of successful engraftment (non-infarcted tissue: 1924 ± 114 perfused capillaries/mm2). The transplantation group was characterized by smaller diastolic and systolic left ventricular volumes, as assessed by intravenous ventriculography, along with thickened infarcts (0.93 ± 0.07 vs. 0.75 ± 0.04 mm, P < 0.020) and lower infarct expansion indices (0.64 ± 0.07 vs. 0.83 ± 0.06, P < 0.023), as determined by post-mortem morphometry of histologic slides. Conclusions. – Transplantation of neonatal cardiomyocytes induced neo-angiogenesis in zones of successful cell engraftment within the scar, which effectively enhanced tissue perfusion.