Improvements of cardiac electrophysiologic stability and ventricular fibrillation threshold in rats with myocardial infarction treated with cardiac stem cells.

摘要

OBJECTIVES: : Arrhythmia is of concern after cardiac stem cell transplantation in repairing infarcted myocardium. However, whether transplantation improved the ventricular fibrillation threshold and whether severe malignant ventricular arrhythmia is induced in the myocardial infarction model are still unclear. We sought to investigate the electrophysiologic characteristics and ventricular fibrillation threshold in rats with myocardial infarction by treatment with allogeneic cardiac stem cells. DESIGN: : Prospective, randomized, controlled study. SETTING: : University-affiliated hospital. SUBJECTS: : Male Sprague-Dawley rats. INTERVENTIONS: : Myocardial infarction was induced in 20 male Sprague-Dawley rats. Two weeks later, animals were randomized to receive 5 x 10 cardiac stem cells labeled with PKH26 in phosphate buffer solution or a phosphate buffer solution-alone injection into the infarcted anterior ventricular-free wall. MEASUREMENTS AND MAIN RESULTS: : Six weeks after the cardiac stem cell or phosphate buffer solution injection, electrophysiologic characteristics and ventricular fibrillation threshold were measured at the infarct area, infarct marginal zone, and noninfarct zone. Labeled cardiac stem cells were observed in 5-mum cryostat sections from each harvested heart. The unipolar electrogram activation recovery time dispersions were shorter in the cardiac stem cell group compared with those at the phosphate buffer solution group (15.5 +/- 4.4 vs. 38.6 +/- 14.9 msecs, p = .000177). Malignant ventricular arrhythmias were significantly (p = .00108) less inducible in the cardiac stem cell group (one of ten) than the phosphate buffer solution group (nine of ten). The ventricular fibrillation thresholds were greatly improved in the cardiac stem cell group compared with the phosphate buffer solution group. Labeled cardiac stem cells were identified in the infarct zone and infarct marginal zone and expressed Connexin-43, von Willebrand factor, alpha-smooth muscle actin, and alpha-sarcomeric actin. CONCLUSIONS: : Cardiac stem cells may modulate the electrophysiologic abnormality and improve the ventricular fibrillation threshold in rats with myocardial infarction treated with allogeneic cardiac stem cells and cardiac stem cell express markers that suggest muscle, endothelium, and vascular smooth muscle phenotypes in vivo.