Colocalization of tenascin and sympathetic nerves in a canine model of nerve sprouting and sudden cardiac death

Abstract

Introduction: Sympathetic nerve sprouting after myocardial infarction (MI) may contribute significantly to the occurrence of ventricular arrhythmia and sudden cardiac death. Tenascin-X (TnX), a matrix protein known to be associated with nerve growth in central and peripheral nerves, also may play a role in cardiac nerve sprouting after MI.

Methods and results: Immunocytochemical staining techniques were used to identify nerves in 5-microm serial sections from 6 normal dogs and 11 dogs with MI. Among the dogs with MI, 4 also received nerve growth factor infusion to the left stellate ganglion. The time between MI to tissue harvest averaged 35.7 +/- 14.4 days. Tyrosine hydroxylase (TH) stain was used to identify sympathetic nerves, and growth-associated protein-43 (GAP-43) was used to identify growing nerves. Polyclonal antibody was obtained for use in identifying TnX. Nerves were evident in both the infarcted and noninfarcted areas. Many nerves were found around blood vessels. A total of 181 nerves in 69 slides were examined: 89 were from noninfarcted myocardium, 4 from infarct, 13 from infarct border zone, and 75 from perivascular regions. Except in normal dogs, all nerves stained positive for TH also stained positive for GAP-43, indicating sympathetic nerve sprouting after MI. In all dogs, the nerves that stained positive for TH also stained positive for TnX.

Conclusion: There is a colocalization of TnX, GAP-43, and TH in sprouted cardiac nerves. These results suggest that TnX is important not only in the existing normal myocardial nerve cells but also in cardiac sympathetic nerve sprouting after MI.