Since in the adult mammalian heart the extent and character of autonomic influences appear to be different between the sinus node and the AV junctional region and because the time course of sympathetic and parasympathetic maturation is both variable and different we propose to examine the hypothesis that a changing differential autonomic control of the sinus node and AV junctional region plays a critical role in the initiation of dysrhythmias such as the bradycardia-induced supraventricular tachycardia so frequently observed in children. The hypothesis considers that early in life cholinergic influences are absolutely or relatively more pronounced in the sinus node than in the AV junctional region. The hypothesis also considers that the responses of the sinus node and AV junctional to adrenergic and cholinergic stimuli increase during maturation (early postnatal life to adulthood) but that the AV junction is at any age far more dependent upon, and considerably more responsive to adrenergic stimulation than the sinus node. To assess this differential autonomic control of the sinus node and AV junction during maturation we will selectively perfuse acetylcholine, norepinephrine, isuprel, phenylephrine, glucagon and histamine agonists into the sinus node artery and AV node artery of beagles age 2 months, 6 and 12 months. These studies will determine how maturation influences the effector (target) organ's responses to individual and combined administration of neurotransmitters in the presence and absence of other naturally occurring compounds. By determining stimulus frequency response curves of sympathetic and parasympathetic nerve stimulation we will assess how maturation differentially influences neurotransmission in the two major centers of automaticity and conduction. Simultaneous stimulation of both autonomic limbs will be performed to examine how maturation affects the interaction between cholinergic and adrenergic stimuli. Special emphasis will be directed toward examining the phase-dependent vagal effects on the sinus node in the presence of adrenergic background influences. Recordings of efferent neurograms both at rest and during reflex adjustments will illustrate and quantitate the age-dependent changes in tonic and phasic neural discharges. These studies should provide strong evidence for or against the viewpoint that autonomic imbalances in the sinus and AV node are largely responsible for the electrical instability of early life.
