Extra-cardiac neural remodeling in humans with cardiomyopathy and arrhythmias

Abstract

5.1 Extra-cardiac neural remodeling in humans with cardiomyopathy and arrhythmias O.A. Ajijola, J.J. Wisco, H.W. Lambert, E.M. Stark, A. Mahajan, M.C. FIshbein, K. Shivkumar (University of California, Los Angeles, CA, USA), (West Virginia University, Morgantown, WV, USA) Background: Intra-myocardial nerve sprouting after myocardial infarction is associated with ventricular arrhythmias (VAs). Whether human stellate ganglia remodel in association with cardiac pathology was unknown. The purpose of our study was to determine whether cardiac pathology is associated with remodeling of the stellate ganglia in humans. Methods and Results: Left stellate ganglia (LSG) were collected from patients undergoing sympathetic denervation for intractable ventricular arrhythmias, and from cadavers, along with intact hearts. Clinical data on patients and cadaveric subjects were reviewed extensively. We classified ganglia from normal; scarred; and non-ischemic cardiomyopathic hearts without scar as NL (n = 3); SCAR (n = 24); and NICM (n = 7), respectively. Within LSG, we measured neuronal size, density, fibrosis, synaptic density and nerve sprouting. Nerve density and sprouting were also quantified in obtained cadaveric hearts. Mean neuronal size in NL, SCAR, and NICM groups were; 320 ± 4 μm, 372 ± 10 μm, and 435± 10 μm (p= 0.002). No significant differences in neuronal density and fibrosis were present between the groups. Synaptic density in SCAR and NICM ganglia were 57.8 ± 11.2um/mm (p= 0.039) and 44.5 ± 7.9um/mm (p= 0.084) respectively, compared to the NL, 17.8 ± 7um/mm (overall p = 0.162). There were no significant differences in LSG nerve sprouting ormyocardial nerve density between the groups. In a porcinemodel of chronic infarcts, neurochemical changes were also observed in addition to increased neuronal size. Conclusions: Neuronal hypertrophy within LSG is associated with chronic cardiomyopathy in humans. Ganglionic and myocardial nerve sprouting and nerve density were not significantly different. A porcine model recapitulates these findings, and demonstrates neurochemical rmodeling. These changes may be related to increased cardiac sympathetic signaling and VAs. Further studies are needed to determine the electrophysiologic consequences of extra-cardiac neuronal remodeling in humans. doi:10.1016/j.autneu.2013.05.030