Little is known about the interactions of the parasympathetic and sympathetic nerves in the developing heart. This application proposes to continue the study of these interactions by removing the autonomic nerves to the heart in various combinations. The autonomic lesions will be accomplished by selective cauterization of the presumptive areas which contribute the parasympathetic pre- and postganglionic and/or the sympathetic postganglionic nerves to the heart. The heart and remaining innervation will then be evaluated by a variety of chemical, morphological and physiological techniques. Residual innervation and effects on growth of the remaining autonomic system will be evaluated by (3H)-choline or (3H)-norepinephine uptake and transmitter concentration. Concentration and affinity of muscarinic acetylcholine and Alpha- and Beta- adrenergic receptors will be determined in aneural atrial and ventricular homogenates using (3H)-QNB, (125I)-BE 2254 and (125I)-pindolol, respectively. Since it has been postulated that innervation plays a role in biochemical development of the heart, (3H)-thymidine incorporation into DNA and (3H)-phenylalanine uptake and incorporation into protein and myosin will be assessed at different stages of development in aneural hearts. The develelopment of the conduction system will be evaluated histochemically and ultrastructurally. Finally, in an attempt to integrate this information and the effect of innervation on functional development of the heart, ECG studies will be done to determine changes in heart rate, conduction potentials and sensitivity of aneural hearts to different drugs. These studies will provide basic information about the influences exerted by the two autonomic systems on each other during development and their influence on the developing heart.
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