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.
Background-Long-term rapid atrial pacing may result in atrial fibrillation (AF) in dogs. Whether there is histological evidence for neural remodeling is unclear. Method and Results-We performed rapid right atrial pacing in 6 dogs for 111Ϯ76 days to induce sustained AF. Tissues from 6 healthy dogs were used as controls. Immunocytochemical staining of cardiac nerves was performed using anti-growth-associated protein 43 (GAP43) and anti-tyrosine hydroxylase (TH) antibodies. In dogs with AF, the density of GAP43-positive and TH-positive nerves in the right atrium was 470Ϯ406 and 231Ϯ126 per mm 2 , respectively, which was significantly (PϽ0.001) higher than the nerve density in control tissues (25Ϯ32 and 88Ϯ40 per mm 2 , respectively). The density of GAP43-positive and TH-positive nerves in the atrial septum was 317Ϯ36 and 155Ϯ85 per mm 2 , respectively, and was significantly (PϽ0.001) higher than the nerve density in control tissues (9Ϯ13 and 30Ϯ7 per mm 2 , respectively). Similarly, the density of GAP43-positive and TH-positive nerves in the left atrium of dogs with AF was 119Ϯ61 and 91Ϯ40 per mm 2 , respectively, which was significantly (PϽ0.001) higher than the nerve density in control tissues (10Ϯ15 and 38Ϯ39 per mm 2 , respectively). Furthermore, in dogs with AF, the right atrium had a significantly higher nerve density than the left atrium. Microscopic examinations revealed an inhomogeneous distribution of cardiac nerves within each sampling site. Conclusions-Significant
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