In mammalian heart autonomic modulations are different between sinus node and AV junction. Since time course of sympathetic and parasympathetic maturation is also different we propose to examine the thesis that a steadily changing differential autonomic control of the sinus node and AV junction plays a critical role in the initiation and maintenance of dysrhythmias that occur early in life. The hypotheses consider that: (1) early in life the inhibitory effect of the vagus on automaticity is greater in sinus node than AV junction; (2) this inhibition increases with maturation; (3) it is modulated by catecholamines; the effect of catechols on automaticity increases during maturation but the AV junctional automaticity is more dependent and more responsive to adrenergic stimuli than the sinus node; (4) cholinergic-adrenergic interactions are different in sinus node and AV junction with little effect on sino-atrial and AV nodal conduction but critically influencing sinus and AV junctional automaticity; (5) the dynamic (phasic) vagal control of AV junctional automaticity parallels that of sinus node automaticity; and (6) vagomimetic action can mediate a non-adrenergic stimulatory effect on sinus node and AV junction. To assess this differential autonomic control of sinus node and AV junction (spatial) during maturation (temporal) we will inject cholinergic and adrenergic agonists and antagonists into the sinus and AV node arteries of beagles 1 to 16 weeks of age and adult dogs. These studies will determine how maturation influences the effector (target) organ's responses to individual and combined administration of neurotransmitters. 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. With simultaneous stimulation of both autonomic limbs we will determine how maturation affects the interaction between cholinergic and adrenergic stimuli. Special emphasis will be directed toward examining the phase-dependent vagal effects on sinus node and AV junction in the presence of various 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 will 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.
