Modulation of QT interval by cardiac sympathetic nerve sprouting and the mechanisms of ventricular arrhythmia in a canine model of sudden cardiac death

Introduction: We previously reported that there is a high incidence of sudd en cardiac death (SCD) in dogs with myocardial infarction (MI), complete AV block (CAVB), and nerve growth factor (NGF) infusion to the left stellate ganglion (LSG). Whether or not QT interval prolongation underlines the mech anism of SCD was unclear. Methods and Results: We analyzed QT intervals in three groups of dogs. All dogs had CAVB and MI. The LSG group (n=9) and right stellate ganglion (RSG) group (n=6) received NGF infusion via the osmotic pumps over a 5-week peri od to LSG and RSG, respectively. The control group (n=6) received no NGF. T he dogs either died suddenly or were sacrificed within 2 to 3 months after MI. Heart rhythm and QT and RR intervals were monitored using implantable c ardioverter defibrillator ECG recordings. There was a time-dependent increa se of QTc intervals in the LSG group and a time-dependent decrease of QTc i ntervals in the RSG group. At the end of NGF infusion, QTc intervals in the LSG group (408 +/- 41 msec) were significantly longer than those in the co ntrol (350 +/- 41 msec; P<0.05) and RSG groups (294<plus/minus>23 msec; P<0 .01). In the LSG group, 4 of 9 dogs died of SCD. There was no SCD in either the RSG or control group. Immunocytochemical staining showed NGF infusion to LSG and RSG resulted in left and right ventricular sympathetic nerve spr outing and hyperinnervation, respectively. Conclusion: NGF infusion to the LSG in dogs with MI and CAVB resulted in in creased QT interval and incidence of ventricular tachycardia, ventricular f ibrillation, and SCD, whereas NGF infusion to the RSG shortened QT interval and reduced the incidence of ventricular tachycardia. These findings indic ate that QT interval prolongation is causally related to the occurrence of ventricular arrhythmia in dogs with nerve sprouting, MI, and CAVB.