Sympathetic Innervation of the Developing Rabbit Heart

Abstract

The sympathetic innervation of the rabbit heart, as a function of age, was studied by measuring the cardiac concentration of catecholamines and observing the anatomic distribution of sympathetic nerves by die monoamine fluorescense technique. The cardiac concentration of norepinephrine in late gestation was quite low; the levels rose progressively after birth to reach adult levels by about three weeks of age. Similar small amounts of epinephrine were found in the hearts at all ages. Substantially less change in adrenal catecholamines accompanied advancing age. At all ages a close correlation was noted between the norepinephrine levels and the histochemical demonstration of sympathetic innervation. Intensely fluorescent, terminal varicosities were observed within large preterminal nerve trunks only in the youngest animals, suggesting that the sympathetic nerves move into, rather than form within, die heart. Chromaffin cells were observed in the hearts at all ages.ADDITIONAL KEY WORDS norepinephrine epinephrine adrenal chromaffin cells myocardial catecholamines• Although the adrenergic nervous system plays an important role in the control of cardiac contractility in the mature mammal, its significance in the perinatal period is not clear. Physiologic and pharmacologic studies undertaken to assess the maturation of the autonomic control of the circulation have been largely concerned with the ability of young animals to respond to various physiologic stimuli, such as hypoxemia and carotid sinus hypotension, or to the injection of catecholamines (1). A number of observations in rabbits of varying ages suggest that the circulaFrom the Cardiology Branch, National Heart Institute, Bethesda, Maryland, and the Department of Pharmacology, University of Pennsylvania, School of Medicine, Philadelphia, Pennsylvania.This investigation was supported in part by U. S. Public Health Service Research Grant 1R01NB0-6707. Dr. Jacobowitz was a recipient of a Research Career Program Award, 5-K 3-N B-13, 935-02, from the National Institutes of Health.Accepted for publication April 29, 1968. tion of the newborn is under no (2), a lesser (3), or a comparable (1) degree of neural control, as compared to the adult. The development of the separate factors constituting an integrated circulatory response-the afferent, central, and efferent components of a vascular reflex, the responsiveness of the peripheral vasculature, and the direct inotropic and chronotropic effects on the myocardium -have not yet been analyzed quantitatively. The objective of the present investigation was to define more clearly the development of sympathetic innervation of the rabbit heart. The cardiac concentration of norepinephrine in fetal, neonatal, and adult animals was employed as an index of the maturity of sympathetic innervation because the heart's stores of norepinephrine are localized almost exclusively in intraceilular storage sites within the terminations of the sympathetic nerves (4). In addition, the monamine fluorescence technique of Falck and O...

Age-Dependence of the Chronotropic Response to Noradrenaline, Acetylcholine and Transmural Stimulation in Isolated Rabbit Atria

“…Findings obtained in the present study that content of noradrenaline in rabbit ventricles increased significantly with development from day 2 to day 30 are quite consistent with the result seen in rabbit whole hearts (5). In addition to increasing the accumulating ability of noradrenaline in adrenergic nerves (14,15), the nerve density in the myocardial wall may also increase with development of the heart.…”

“…In addition to increasing the accumulating ability of noradrenaline in adrenergic nerves (14,15), the nerve density in the myocardial wall may also increase with development of the heart. In their fluorescence histochemical study, Friedman et al (5) suggested that a significant proportion of noradrenaline measured in the newborn heart resides in the preterminal nerve trunks and therefore may not be in close anatomical proximity to adrenergic receptors in the myocardial cell. In the present study, however, the response to tyramine was not appreciably altered with development.…”

“…Autonomic innervation in the heart develops gradually after birth (4,5), and the response to stimulation of the nerves in the heart in situ is altered with development (6, 7).…”

Inotropic Response of the Neonatal Canine Myocardium to Dopamine

“…Because of this relative lack of sympathetic innervation, ventricular myocardial levels of norepinephrine are reduced in the young animal (6). It follows, therefore, that decreased responsiveness of neonatal myocardial tissue to agents that act in part by releasing norepinephrine would be expected.…”

Heart block after intravenous lidocaine in an infant

“…In addition, newborn rabbit hearts have low epinephrine stores and decreased sympathetic innervation. 28 Because the newborn has an immature conduction system and sympathetic innervation she may be susceptible to toxicity even from accepted therapeutic doses of lidocaine. Indeed, foetal hearts bathed with therapeutic levels of amide local anaesthetic solutions demonstrate a decreased spontaneous contraction rate and increased A-V conduction times.…”