Dynamic remodeling of the guinea pig intrinsic cardiac plexus induced by chronic myocardial infarction
Myocardial infarction (MI) is associated with remodeling of the heart and neurohumoral control systems. The objective of this study was to define time-dependent changes in intrinsic cardiac (IC) neuronal excitability, synaptic efficacy, and neurochemical modulation following MI. MI was produced in guinea pigs by ligation of the coronary artery and associated vein on the dorsal surface of the heart. Animals were recovered for 4, 7, 14, or 50. days. Intracellular voltage recordings were obtained in whole mounts of the cardiac neuronal plexus to determine passive and active neuronal properties of IC neurons. Immunohistochemical analysis demonstrated an immediate and persistent increase in the percentage of IC neurons immunoreactive for neuronal nitric oxide synthase. Examination of individual neuronal properties demonstrated that afterhyperpolarizing potentials were significantly decreased in both amplitude and time course of recovery at 7. days post-MI. These parameters returned to control values by 50. days post-MI. Synaptic efficacy, as determined by the stimulation of axonal inputs, was enhanced at 7. days post-MI only. Neuronal excitability in absence of agonist challenge was unchanged following MI. Norepinephrine increased IC excitability to intracellular current injections, a response that was augmented post-MI. Angiotensin II potentiation of norepinephrine and bethanechol-induced excitability, evident in controls, was abolished post-MI. This study demonstrates that MI induces both persistent and transient changes in IC neuronal functions immediately following injury. Alterations in the IC neuronal network, which persist for weeks after the initial insult, may lead to alterations in autonomic signaling and cardiac control. © 2013 Elsevier B.V.
Autonomic Neuroscience: Basic and Clinical
Hardwick, Jean C.; Ryan, Shannon E.; Beaumont, Eric; Ardell, Jeffrey L.; and Southerland, E. Marie, "Dynamic remodeling of the guinea pig intrinsic cardiac plexus induced by chronic myocardial infarction" (2014). Faculty Articles Indexed in Scopus. 940.