Aggregates of postganglionic cell bodies are localized in the fat pads overlying the entrance of right pulmonary veins (PVFP) into the atrium and at the junction of inferior vena cava and inferior left atrium (IVC-ILA), excision of which interrupts all vagal input to the sinoatrial node (SAN) and atrioventricular node (AVN), respectively. Interruption of one does not interfere with vagal regulation by the other. Thus, the PVFP serves as the ganglionic synapse for parasympathetic regulation of SAN regulation of cardiac automaticity, and IVC-ILA as parasympathetic modulation of AVN control of A-V conduction. Research proposed will examine the morphologic characteristics of these separate cardiac ganglia and their selective functional control of SAN and/or AVN. Both light and electron microscopic studies are proposed, together with electrophysiologic examination of possible interactions between sympathetic and parasympathetic inputs. Tentative probes into possible roles of peptidergic influences are recognized. Electro-physiologic activity of the cardiac neurons and their potential roles in intrinsic cardiac innervation circuits will be examined. The precise anatomical and functional pathways from the PVFP to the SAN will be determined, as will those pathways from IVC-ILA to AVN regions. The question is posed whether neural intercommunication pathways exist between SAN and AVN; between PVFP and AVN; and between IVC-ILA and SAN? Unilateral cervical vagotomy results in marked functional adjustments in control exerted by the remaining, previously nondominant vagus, over SAN and/or AVN regulation of cardiac function. This implies dramatic changes in intrinsic neural terminations on the automatic cells of SAN and the conductile tissues of AVN. Muscarinic receptor binding characteristics in the SAN, AVN, atrial, and ventricular musculature will be carefully quantitated in control hearts, hearts sustaining total preganglionic parasympathectomy, or selective parasympathectomy of either SAN or AVN. Both receptor densities and receptor affinities will be measured in canine hearts before and after each of these selective denervation procedures. Tissue samples will also be examined under light and electron microscopy from these animals, with emphases upon axoaxonic, axodendritic, and axosomatic alterations in morphology. Similarly, do extraneuronal interactions from small, intensely fluorescent (SIF) cells exist among these cardiac ganglia, and are they or their interacting neurons, altered by pre- or postganglionic interventions?

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
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Cardiovascular and Pulmonary Research A Study Section (CVA)
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Loyola University Chicago
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