Profound Cardiac Sympathetic Denervation Occurs in Parkinson Disease

In the last few years, cardiac sympathetic dysfunction in Parkinson disease (PD) has been postulated on the basis of decreased cardiac uptake of sympathoneural imaging tracers. However, the pathological substrate for the dysfunction remains to be established. We examined the left ventricular anterior wall from postmortem specimens with immunohistochemical staining for tyrosine hydroxylase (TH), neurofilament (NF) and S‐100 protein in PD patients and control subjects, and quantified the immunoreactive areas. As TH‐immunoreactive axons nearly disappeared and NF‐immunoreactive axons drastically decreased in number, the morphological degeneration of the cardiac sympathetic nerves in PD was confirmed. Quantitative analysis showed that sympathetic nerves were preferentially involved. Triple immunofluorolabeling for NF, TH, and myelin basic protein showed clearly the profound involvement of sympathetic axons in PD. The extent of involvement of the cardiac sympathetic nerves seems likely to be equivalent to that in the central nervous system, including the nigrostriatal dopaminergic system. PD affects the cardiac sympathetic nervous system profoundly as well as nigrostriatal dopaminergic system.

[1]  K. Wakabayashi,et al.  Neuropathology of autonomic nervous system in Parkinson's disease. , 1997, European neurology.

[2]  K. Nakajima,et al.  Peripheral sympathetic dysfunction in patients with Parkinson’s disease without autonomic failure is heart selective and disease specific , 2000, European Journal of Nuclear Medicine.

[3]  B. Jarrott,et al.  Differential effects of surgical sympathectomy on rat heart concentrations of neuropeptide Y-immunoreactivity and noradrenaline. , 1987, Journal of the autonomic nervous system.

[4]  P. Mcgeer,et al.  ENZYMES ASSOCIATED WITH THE METABOLISM OF CATECHOLAMINES, ACETYLCHOLINE AND GABA IN HUMAN CONTROLS AND PATIENTS WITH PARKINSON'S DISEASE AND HUNTINGTON'S CHOREA , 1976, Journal of neurochemistry.

[5]  D. Goldstein,et al.  Orthostatic hypotension from sympathetic denervation in Parkinson’s disease , 2002, Neurology.

[6]  I. Kopin,et al.  6-Fluorocatecholamines as false adrenergic neurotransmitters. , 1983, The Journal of pharmacology and experimental therapeutics.

[7]  W. Rogers,et al.  Imaging the primate adrenal medulla with [123I] and [131I] meta-iodobenzylguanidine: concise communication. , 1981, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[8]  H. Huikuri,et al.  Ambulatory ECG and analysis of heart rate variability in Parkinson's disease , 2001, Journal of neurology, neurosurgery, and psychiatry.

[9]  C. Owman,et al.  Vasoactive intestinal polypeptide and acetylcholine coexist with neuropeptide Y, dopamine-β-hydroxylase, tyrosine hydroxylase, substance P or calcitonin gene-related peptide in neuronal subpopulations in cranial parasympathetic ganglia of rat , 1992, Cell and Tissue Research.

[10]  T. Uchihara,et al.  Dual enhancement of triple immunofluorescence using two antibodies from the same species , 2004, Journal of Neuroscience Methods.

[11]  Freimut Juengling, Jungling, Jüngling,et al.  Scintigraphic differentiation between two forms of primary dysautonomia early after onset of autonomic dysfunction: value of cardiac and pulmonary iodine-123 MIBG uptake , 2000, European Journal of Nuclear Medicine.

[12]  P. Molinoff,et al.  Biochemistry of catecholamines. , 1971, Annual review of biochemistry.

[13]  Norio Ishizuka,et al.  Triple Immunofluorolabeling with Two Rabbit Polyclonal Antibodies and a Mouse Monoclonal Antibody Allowing Three-dimensional Analysis of Cotton Wool Plaques in Alzheimer Disease , 2003, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[14]  P. Schmid,et al.  Innervation patterns of the middle cervical - stellate ganglion complex in the rat , 1990, Neuroscience Letters.

[15]  T. Kondo,et al.  Catecholamine-related enzymes and the biopterin cofactor in Parkinson's disease and related extrapyramidal diseases. , 1984, Advances in neurology.

[16]  N. Christensen,et al.  Norepinephrine, Epinephrine, and Dopamine Contents of the Cardiovascular System in Long-term Diabetics , 1976, Diabetes.

[17]  K. Wakabayashi,et al.  Sympathetic cardiac denervation in Parkinson's disease and pure autonomic failure but not in multiple system atrophy , 2002, Journal of neurology, neurosurgery, and psychiatry.

[18]  D. Goldstein,et al.  Progressive loss of cardiac sympathetic innervation in Parkinson's disease , 2002, Annals of neurology.

[19]  H. Hattori,et al.  [123I] meta-iodobenzylguanidine myocardial scintigraphy differentiates corticobasal degeneration from Parkinson's disease. , 2003, Internal medicine.

[20]  S. Nekolla,et al.  Myocardial Efficiency and Sympathetic Reinnervation After Orthotopic Heart Transplantation: A Noninvasive Study With Positron Emission Tomography , 2001, Circulation.

[21]  O. Hornykiewicz,et al.  The neurochemistry of Parkinson's disease: effect of L-dopa therapy. , 1975, The Journal of pharmacology and experimental therapeutics.

[22]  K. Wakabayashi,et al.  Different histopathology accounting for a decrease in myocardial MIBG uptake in PD and MSA , 2001, Neurology.

[23]  T. Gray,et al.  Monoamine- and histamine-synthesizing enzymes and neurotransmitters within neurons of adult human cardiac ganglia. , 1999, Circulation.

[24]  P. Slootweg,et al.  INNERVATION OF THE ENDOMYOCARDIUM IN THE FIRST PERIOD AFTER HEART TRANSPLANTATION , 1993, Transplantation.

[25]  R. Coggeshall,et al.  Categories of axons in the inferior cardiac nerve of the cat , 1978, The Journal of comparative neurology.

[26]  D. Taylor,et al.  Surgical sympathectomy of the heart in rodents and its effect on sensitivity to agonists. , 1985, The Journal of pharmacology and experimental therapeutics.

[27]  D. Zipes,et al.  Epicardial Phenol Interrupts Refractory Period Responses to Sympathetic but Not Vagal Stimulation in Canine Left Ventricular Epicardium and Endocardium , 1980, Circulation research.

[28]  L. Metman,et al.  Cardiac Sympathetic Denervation in Parkinson Disease , 2000, Annals of Internal Medicine.

[29]  M. Yacoub,et al.  Immunohistochemical demonstration of human cardiac innervation before and after transplantation. , 1990, Circulation research.

[30]  M. Yoshita,et al.  Differentiation of idiopathic Parkinson's disease from striatonigral degeneration and progressive supranuclear palsy using iodine-123 meta-iodobenzylguanidine myocardial scintigraphy , 1998, Journal of the Neurological Sciences.

[31]  R. Anderson,et al.  Postmortem changes in the immunohistochemical demonstration of nerves in human ventricular myocardium * , 1998, Journal of anatomy.

[32]  W. Nayler,et al.  Concentration of catecholamines in human cardiac muscle. , 1979, British heart journal.

[33]  K. Iwanaga,et al.  Lewy body–type degeneration in cardiac plexus in Parkinson’s and incidental Lewy body diseases , 1999, Neurology.

[34]  E. W. van Stee Autonomic innervation of the heart. , 1978, Environmental health perspectives.

[35]  A. Takahashi Autonomic nervous system disorders in Parkinson's disease. , 1991, European neurology.

[36]  S. Orimo,et al.  123I-metaiodobenzylguanidine myocardial scintigraphy in Parkinson’s disease , 1999, Journal of neurology, neurosurgery, and psychiatry.

[37]  K. Yano,et al.  Histological study on the distribution of autonomic nerves in the human heart , 2003, Heart and Vessels.

[38]  K. Jellinger,et al.  Homospecific activity (activity per enzyme protein) of tyrosine hydroxylase increases in parkinsonian brain , 2005, Journal of Neural Transmission.