(Circulation. 2000;101:1960.)
© 2000 American Heart Association, Inc.
Clinical Investigation and Reports |
Relationship Between Regional Cardiac Hyperinnervation and Ventricular Arrhythmia
From the Division of Cardiology (J.-M.C., J.B.H., W.W.L., A.C.L., T.-J.W., P.-S.C.), Department of Medicine, Division of Cardiothoracic Surgery (L.C., T.A.D.), Department of Surgery, Cedars-Sinai Medical Center and University of California Los Angeles School of Medicine; Department of Pathology (M.C.F., I.P.S.), University of California Los Angeles School of Medicine; Department of Pathology (P.L.W.), Veterans Affairs Medical Center and University of California San Diego; and Division of Neurology (L.S.C.), Childrens Hospital Los Angeles and University of Southern California Keck School of Medicine.
Correspondence to Lan S. Chen, MD, Division of Neurology 82, Childrens Hospital Los Angeles, 4650 Sunset Blvd, Los Angeles, CA 90027.
Background—Sympathetic nerve activity is known to be important in ventricular arrhythmogenesis, but there is little information on the relation between the distribution of cardiac sympathetic nerves and the occurrence of spontaneous ventricular arrhythmias in humans.
Methods and Results—We studied 53 native hearts of transplant recipients, 5 hearts obtained at autopsy of patients who died of noncardiac causes, and 7 ventricular tissues that had been surgically resected from the origin of ventricular tachycardia. The history was reviewed to determine the presence (group 1A) or absence (group 1B) of spontaneous ventricular arrhythmias. Immunocytochemical staining for S100 protein, neurofilament protein, tyrosine hydroxylase, and protein gene product 9.5 was performed to study the distribution and the density of sympathetic nerves. The average left ventricular ejection fraction was 0.22±0.07. A total of 30 patients had documented ventricular arrhythmias, including ventricular tachycardia and sudden cardiac death. A regional increase in sympathetic nerves was observed around the diseased myocardium and blood vessels in all 30 hearts. The density of nerve fibers as determined morphometrically was significantly higher in group 1A patients (total nerve number 19.6±11.2/mm2, total nerve length 3.3±3.0 mm/mm2) than in group 1B patients (total nerve number 13.5±6.1/mm2, total nerve length 2.0±1.1 mm/mm2, P<0.05 and P<0.01, respectively).
Conclusions—There is an association between a history of spontaneous ventricular arrhythmia and an increased density of sympathetic nerves in patients with severe heart failure. These findings suggest that abnormally increased postinjury sympathetic nerve density may be in part responsible for the occurrence of ventricular arrhythmia and sudden cardiac death in these patients.
Key Words: nervous system • tachycardia • death, sudden • cardiomyopathy
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