Figure 2 summarizes the current working hypothesis for neurohumoral interactions involved in the control of cardiac function. Data indicate that a hierarchy of peripheral autonomic neurons function interdepen-dently via nested feedback loops to regulate cardiac function on a beat-to-beat basis. Figure 2 summarizes the emerging concept of neural control of the heart as mediated by intrathoracic extracardiac and intracardiac neurons, which are continuously influenced by descending projections from higher centers in the spinal cord, brain stem, and suprabulbar regions. Each successive synaptic relay point within this autonomic outflow, from the brain stem to the heart, is in turn influenced by afferent feedback from various cardiopulmonary and vascular afferent receptors. Accumulating evidence suggests that there may be at least four functionally distinct neuronal types within the intrinsic cardiac nerve plexus (see earlier discussion): parasympathetic postganglionic efferent neurons (1,29,34,46,51,115,135), local circuit neurons (20,21,53,119,136), adrenergic postganglionic efferent neurons (25, 34, 84-86,140), and afferent neurons (5, 20, 21, 53). Local circuit and cardiac afferent neurons also lie within intrathoracic extracardiac ganglia, along with sympathetic postganglionic neurons (15, 18). With respect to intrathoracic autonomic ganglia, cholinergic and adrenergic efferent neurons in these ganglia represent the output elements that project axons to cardiac electrical and mechanical tissues. Local circuit neurons interconnect adjacent neurons within one ganglion or link neurons in separate clusters of intrathoracic ganglia (14, 136). These interneurons are presumably involved in the coordination of neuronal activity within these peripheral autonomic ganglia, likely providing the underlying inputs necessary for the maintenance of basal autonomic neuronal discharge. Intrathoracic affer-
ent neurons provide mechanosensitive and chemosensi-tive inputs from cardiopulmonary regions directly to intrinsic cardiac and extracardiac neurons, forming the basis of the intrathoracic neural feedback system (5, 65). Superimposed on activities generated by neurons in peripheral autonomic ganglia are efferent inputs from preganglionic neurons in the brain stem and spinal cord that together exert tonic influences on regional cardiac tone (6, 7, 35). CNS preganglionic inputs are, in turn, influenced by inputs from higher centers in the central nervous system and by afferent feedback from central and peripheral sensory afferent neurons (9-11).
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