Biological pacemaker implanted in @entity235 left bundle branch provides XXXX that have physiologically acceptable rates.

@entity235 @entity67 @entity1165 @entity70866
BACKGROUND: We hypothesized that administration of the @entity70866 gene to the left bundle-branch (LBB) system of intact @entity235 would provide pacemaker function in the physiological range of heart rates. METHODS AND RESULTS: An adenoviral construct incorporating @entity70866 and green fluorescent protein (GFP) as a marker was injected via catheter under fluoroscopic control into the posterior division of the LBB. Controls were injected with an adenoviral construct of GFP alone or saline. Animals were monitored electrocardiographically for up to 7 days after surgery, at which time they were anesthetized and subjected to vagal stimulation to permit emergence of escape pacemakers. Hearts were then removed and injection sites visually identified and removed for microelectrode study of action potentials, patch clamp studies of pacemaker current, and/or immunohistochemical studies of @entity70866 . For 48 hours postoperatively, 7 of 7 animals subjected to 24-hour ECG monitoring showed multiple ventricular premature depolarizations and/or @entity1165 attributable to injection-induced injury. Thereafter, sinus rhythm prevailed. During vagal stimulation, @entity70866 -injected @entity235 showed rhythms originating from the left ventricle, the rate of which was significantly more rapid than in the controls. Excised posterior divisions of the LBB from @entity70866 -injected animals manifested automatic rates significantly greater than the controls. Isolated tissues showed immunohistochemical and biophysical evidence of overexpressed @entity70866 . CONCLUSIONS: A gene-therapy approach for induction of biological pacemaker activity within the LBB system provides @entity67 that have physiologically acceptable rates. Long-term stability and feasibility of the approach remain to be tested.
