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.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL031536-06
Application #
3342740
Study Section
Cardiovascular Study Section (CVA)
Project Start
1983-09-30
Project End
1991-11-30
Budget Start
1988-12-01
Budget End
1989-11-30
Support Year
6
Fiscal Year
1989
Total Cost
Indirect Cost
Name
University of Alabama Birmingham
Department
Type
Schools of Medicine
DUNS #
004514360
City
Birmingham
State
AL
Country
United States
Zip Code
35294
Neely, B H; Urthaler, F (1992) Quantitative effects of sympathetic and vagal nerve stimulations on sinus and AV junctional rhythms. J Auton Nerv Syst 37:109-20
Neely, B H; Urthaler, F; Smith, L R (1987) The effects of negative chronotropic interventions on sinus node recovery time. Basic Res Cardiol 82:92-100
Urthaler, F; Neely, B H; Hageman, G R et al. (1986) Differential effects of sympathetic activity on AV junctional automaticity and AV conduction. Basic Res Cardiol 81:497-507
Rosenshtraukh, L V; Urthaler, F; Anjukhovsky, E P et al. (1986) Serial production of controlled periods of temporary heart block used to unmask and assess latent ventricular automaticity during experimental acute myocardial ischemia. J Am Coll Cardiol 8:95A-103A
Urthaler, F; Rosenshtraukh, L V; Hageman, G R et al. (1986) Differential modulation of autonomic activity by ethmozin and ethacizin (analog of ethmozin) on the canine sinus node and atrioventricular junction. J Am Coll Cardiol 8:86A-94A
Urthaler, F (1986) Ventricular echo beats during ventricular pacing or junctional bradycardia: studies in the normal canine heart. Am Heart J 111:672-8
Urthaler, F (1986) Role of calcium channel blockers in clinical medicine. Am J Med Sci 292:217-30
Urthaler, F; Neely, B H; Hageman, G R et al. (1986) Differential sympathetic-parasympathetic interactions in sinus node and AV junction. Am J Physiol 250:H43-51
Hageman, G R; Neely, B H; Urthaler, F (1986) Cardiac autonomic efferent activity during baroreflex in puppies and adult dogs. Am J Physiol 251:H443-7
Urthaler, F; Rosenshtraukh, L V; Walker, A A et al. (1986) Differential inotropic actions of ethmozine and ethacizin (diethylamine analog of ethmozine). Am Heart J 111:462-5