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Developmental changes in modulation of cardiac repolarization by sympathetic stimulation: the role of beta- and
1Department of Pharmacology, College of Physicians and Surgeons, Columbia University, New York 10032, USA.
Introduction:
Our goals were to study the role of development in determining the cardiac effects of sympathetic neural activation, and to identify the roles of alpha- and beta-adrenergic receptor-mediated pathways in modulating the effects of sympathetic stimulation.
Methods And Results:
We compared responses of young and adult canine hearts in situ to right, left, and bilateral stellate ganglion stimulation. We focused on changes in heart rate, rhythm, QT interval, rate-corrected QT interval (QTc), and T wave amplitude. Right stellate stimulation (RSS) induced more pronounced sinus tachycardia in adult than young animals. Left stellate stimulation (LSS) induced junctional tachycardia in adult more than young animals. In adults, LSS and RSS prolonged QTc (LSS > RSS), whereas 1-week-olds manifested QTc shortening with RSS. LSS also increased T wave amplitude, most markedly in adults. In all studies, bilateral stellate stimulation induced responses intermediate between those seen with RSS and LSS. beta-Adrenergic blockade (propranolol) abolished all responses to LSS in adult hearts, but alpha-blockade (prazosin) attenuated only the LSS-induced prolongation in QTc.
Conclusion:
In the postnatal modulation of cardiac rhythm, rate, and repolarization by the sympathetic nervous system, beta-adrenergic receptors play a major role at all ages, whereas alpha-adrenergic receptors play a lesser role, which is manifested only in adults. Moreover, expression of junctional tachycardias, which are beta-adrenergically modulated, is seen only in the adults.