The applicant proposes to investigate the physiologic importance of the intrinsic cardiac nervous system. The applicant's principal objective is to identify the specific deficits within the intrinsic cardiac ganglia and at the myocyte receptor-effector synaptic junctions that occur subsequent to decentralization of the heart and/or adrenalectomy. For this purpose five specific aims have been defined.
Specific Aim 1. To determine if prolonged loss of extrinsic nerve inputs to the heart and/or loss of adrenal medullary support modifies basal nerve activity and synaptic interactions within the in vivo intrinsic cardiac ganglia in response to application of specific cholinergic and non-cholinergic agonists and antagonists.
Specific Aim 2. To determine if prolonged loss of extrinsic nerve inputs to the heart and/or loss of adrenal medullary support alters the membrane properties and synaptic efficacy of cardiac neurons. Using intracellular microelectrode techniques applied to in vitro whole mount intracardiac ganglia, somatic responses to specific cholinergic and non-cholinergic agonists and antagonists will be evaluated prior to and during electrical stimulation of interganglionic nerves.
Specific Aim 3. Using receptor autoradiography, to determine if prolonged loss of extrinsic nerve inputs to the heart and/or prolonged loss of adrenal medullary support modifies specific cholinergic, adrenergic and angiotensin II receptor densities and distributions within the intrinsic cardiac ganglia or within the electrical and contractile tissues of the canine heart.
Specific Aim 4. To determine if prolonged loss of extrinsic nerve inputs to the heart and/or prolonged loss of adrenal medullary support modifies signal transduction within cardiac myocytes.
Specific Aim 5. To determine if restoration of circulating catecholamines alleviates the cardiodepression associated with chronic adrenalectomy with and without concurrent prolonged loss of extrinsic nerve inputs to the heart.
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