Effects on Arrhythmogenesis and Arrhythmic Threshold of Injection of Autologous Fibroblasts into Myocardial Infarcts in Adult Pigs

摘要

Myocardial dysfunction is strongly associated with a higher rate of ventricular arrhythmia and sudden death. Clinical studies indicate that intramyocardial injection of autologous cells to augment contractile function may modify the arrhythmogenic substrate. The aim of this study was to assess the effects of epicardial injections of autologous dermal fibroblasts in infarcted pigs on the incidence of spontaneous and induced ventricular tachycardia. In eight pigs, myocardial infarction was induced, and the skin was excised for fibroblast isolation, culture, and labeling with bromodeoxyuridine (BrdU). After 3 weeks, animals received epicardial injection of the autologous fibroblasts (n = 4) or saline (n = 4) across the scarred and border zone regions, with continuous ECG monitoring for the following 4 weeks. Electrophysiologic study with programmed stimulation was performed before injections and at sacrifice, and histological analysis was performed. ECG monitoring showed that the fibroblast group had a lower total number of ectopic ventricular complexes per day when compared to the control group (58 ± 119 versus 478 ± 1,308 respectively; p = 0.013) and fewer episodes of non-sustained ventricular arrhythmia per day (0 episodes versus 31 ± 148 respectively; p = 0.001). Inducibility during programmed ventricular stimulation was no different between the groups. Histological analysis disclosed the presence of viable BrdU-labeled cells in injected areas. This study showed that fibroblasts can be safely transplanted in an infarcted heart and survive for at least 4 weeks. Fibroblast injection did not increase the inducibility of ventricular tachycardia, and reduced the incidence of spontaneous ventricular tachycardia.