Dynamic remodeling of the guinea pig intrinsic cardiac plexus induced by chronic myocardial infarction

Abstract

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.

Pathological effects of chronic myocardial infarction on peripheral neurons mediating cardiac neurotransmission

“…In the porcine model, chronic ventricular infarction is accompanied by similar changes in somata of the stellate ganglia (SG) (Ajijola et al, 2015). In agreement with such histological evidence, i n vitro intracellular studies of IC neurons derived from chronic MI animals have demonstrated enhanced neuronal excitability, altered synaptic efficacy, and adaptive reorganization of neurochemical phenotypes and neuromodulation within the intrinsic cardiac nervous system (Hardwick et al, 2014; Hardwick et al, 2008). In fact, it is becoming evident that the ICNS, as the final integrator of cardiac neuraxial control, can undergo significant reorganization – both anatomical and functional – during the evolution of chronic MI (Rajendran et al, 2016).…”

Remodeling of stellate ganglion neurons after spatially targeted myocardial infarction: Neuropeptide and morphologic changes

“…The lack of regionality in neural remodeling from left and right-sided MI may reflect a difference in how afferent (transduction of signals following an MI) and efferent sympathetic activation reach the heart. A more important explanation is that the intrinsic cardiac network (ICN) 18 is the primary site transducing cardiac injury to the CNS, and subsequent distribution of remodeling-inducing signals to both stellate ganglia 19, 20 via increased sympathetic outflow. Whether there is differential remodeling in the ICN to left and right-sided MI remains unknown.…”

Intrinsic cardiac ganglia and acetylcholine are important in the mechanism of ischaemic preconditioning

“…The massive sensory and ischaemic trauma associated with myocardial infarction (MI) induces dynamic morphological and phenotypic remodelling of the intrinsic cardiac nervous system, not limited to the infarcted region [25]. A ‘neural sensory border zone’ of infarction appears, with those afferents within the infarcted region becoming less sensitive, and those in the border and remote regions preserved or enhanced [57].…”