This application consists of two-complementary experiments to determine the role of neurons intrinsic to the heart in the controlling cardiac function in the unanesthetized dog. In Experiment 1 we will test the hypothesis that ganglia located within the """"""""posterior atrial fat pad"""""""" (PAFTP) inhibit sympathetically mediated cardio-acceleration and positive inotropism, but not AV-nodal conduction or vagal HR slowing. Controlled changes in cardiac autonomic nervous activity will be produced using behavioral conditioning. Dogs (n=16) will be trained by following a 30 sec. tone with a 1/2 sec. shock. The conditional response to the tone consists of a rapid initial (Phase 1) tachycardia mediated by parasympathetic withdrawal followed by a larger, but less rapid cardio-acceleration do to increased sympathetic activity. This latter """"""""Phase 2"""""""" is accompanied by an increase ina the amplitude of the first time derivative of left ventricular pressure [d(LVP)/dt, an index of ventricular inotropism]. Finally, there ia a positive dromotropism due to changes in both sympathetic and parasympathetic nervous activity. This integrated resposne pattern will be compared in sham-operated dogs and animals whose PAFP ganglia have been surgically removed. If the hypothesis is correct, the selectively denervated dogs will show no changes in parasympathetic control of resting HR (assessed by spectral analysis) or int he Phase 1 tachycardia, but there will be a significant increase int he sympathetically mediated Phase 2 HR and d(LVP)/dt conditional responses. In Experiment 2 we will test the hypothesis that SA-nodal and AV-nodal function are coordinated by """"""""intra- cardiac reflexes"""""""" involving an intrinsic ganglionated nervous plexus within the """"""""pulmonary vein fat pad (PVFP)' and another plexus at the juncture of the inferior vena cava and the inferior left atrium (IVC-ILA). Conditional changes in HR and AV-nodal conduction will be compared in sham-operated dogs (from Exp. 1), dogs with surgical removal of the PVFP ganglia and animals with ablated IVC-ILA neurons (n-10). In dogs with intact cardiac innervation we anticipate that Phases 1 and 2 of the conditional HR response will be accompanied by corresponding increases in AV-nodal conduction velocity; this positive dromotropic response must be neurally mediated because increases in HR, per se, slow AV-nodal conduction. If this coordination of SA- and AV-nodal conduction occurs within the cardiac intrinsic cardiac nerve plexus, rather than at higher levels within the nervous system, we will be able to decouple the chronotropic and dromotropic components of the conditional response pattern by selective surgical ablation at key points within this nerve network. These experiments will show for the first time the role of the """"""""heart brain"""""""" in controlling and coordinating cardiac chronotropic, dromotropic and inotropic responses in the unanesthetized subject.
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