Electrocardiographic QT prolongation after ablation of the nodose placode in the chick embryo: a developmental model of the idiopathic long QT syndrome.
Electrocardiographic abnormalities characteristic of the idiopathic long QT syndrome are thought to be caused by an imbalance of sympathetic activity in the heart. Recent evidence indicates that autonomic and sensory innervation density in the end-organ is modulated by reciprocal interactions. Ablation of one neuronal population allows reciprocal increases in growth of the remaining nerves. To test whether QT prolongation could be produced in chick embryos by altering sensory innervation to the heart, microcautery was used to ablate premigratory areas of the right nodose placode, a coalescence of cells in the embryonic ectoderm that generates neurons providing sensory innervation to the heart via the inferior ganglion of the vagus (nodose ganglion). After functional autonomic innervation was established, three-lead ECG were obtained in embryos with the right nodose placode ablated (experimental) and in sham-operated controls (sham) at incubation days 17-20 in a controlled temperature environment. Electrocardiograms were analyzed for RR and QT intervals. The QT interval was corrected for heart rate using the formula QTc = QT/(RR)1/2 using an average of ten complexes. Compared with shams (n = 8), experimental embryos (n = 7) had significantly longer QTc (0.339 +/- 0.005 versus 0.318 +/- 0.004), and slower heart rates (RR = 0.29 +/- 0.005 versus 0.27 +/- 0.007). These findings mimic those in children with the idiopathic long QT syndrome. Experimental manipulation of the sensory innervation to the heart in the chick embryo via the nodose placode may provide an animal model to improve understanding of the pathogenesis of the idiopathic long QT syndrome.
Department of Anatomy, Medical College of Georgia, Augusta 30912-2000.
J L
JL
Christiansen
H A
HA
Stadt
M J
MJ
Mulroy
M L
ML
Kirby
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000503:physiopathology*; D002642:Chick Embryo; D004195:Disease Models, Animal; D004562:Electrocardiography; D006321:Heart / Q000196:embryology*; D006329:Heart Conduction System / Q000502:physiology*; D008133:Long QT Syndrome / Q000503:physiopathology*