Nerve sprouting and sudden cardiac death.
The factors that contribute to the occurrence of sudden cardiac death (SCD) in patients with chronic myocardial infarction (MI) are not entirely clear. The present study tests the hypothesis that augmented sympathetic nerve regeneration (nerve sprouting) increases the probability of ventricular tachycardia (VT), ventricular fibrillation (VF), and SCD in chronic MI. In dogs with MI and complete atrioventricular (AV) block, we induced cardiac sympathetic nerve sprouting by infusing nerve growth factor (NGF) to the left stellate ganglion (experimental group, n=9). Another 6 dogs with MI and complete AV block but without NGF infusion served as controls (n=6). Immunocytochemical staining revealed a greater magnitude of sympathetic nerve sprouting in the experimental group than in the control group. After MI, all dogs showed spontaneous VT that persisted for 5.8+/-2.0 days (phase 1 VT). Spontaneous VT reappeared 13.1+/-6.0 days after surgery (phase 2 VT). The frequency of phase 2 VT was 10-fold higher in the experimental group (2.0+/-2.0/d) than in the control group (0.2+/-0.2/d, P<0.05). Four dogs in the experimental group but none in the control group died suddenly of spontaneous VF. We conclude that MI results in sympathetic nerve sprouting. NGF infusion to the left stellate ganglion in dogs with chronic MI and AV block augments sympathetic nerve sprouting and creates a high-yield model of spontaneous VT, VF, and SCD. The magnitude of sympathetic nerve sprouting may be an important determinant of SCD in chronic MI.
Cao
J M
JM
Division of Cardiology, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Chen
L S
LS
KenKnight
B H
BH
Ohara
T
T
Lee
M H
MH
Tsai
J
J
Lai
W W
WW
Karagueuzian
H S
HS
Wolf
P L
PL
Fishbein
M C
MC
Chen
P S
PS
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use; D000818:Animals; D016757:Death, Sudden, Cardiac / Q000473:pathology / Q000517:prevention & control; D004285:Dogs; D006321:Heart / Q000294:innervation*; D006327:Heart Block / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D009203:Myocardial Infarction / Q000473:pathology / Q000503:physiopathology*; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009416:Nerve Regeneration / Q000187:drug effects / Q000502:physiology*; D013233:Stellate Ganglion / Q000187:drug effects / Q000473:pathology* / Q000502:physiology; D017180:Tachycardia, Ventricular / Q000503:physiopathology; D014693:Ventricular Fibrillation / Q000503:physiopathology
C488871:7S nerve growth factor protein, human; D000319:Adrenergic beta-Antagonists; D009414:Nerve Growth Factors