Alteration of parasympathetic/sympathetic ratio in the infarcted myocardium after Schwann cell transplantation modified electrophysiological function of heart: a novel antiarrhythmic therapy.
BACKGROUND
Neural remodeling after myocardial infarction (MI) may cause fatal ventricular arrhythmia. Schwann cells (SCs), which are important for neurogenesis, are dramatically reduced after MI. We investigated the feasibility of modifying nervous system regeneration after MI and the efficacy by which it may prevent ventricular arrhythmia following SC transplantation.


RESULTS
Immediately after creation of MI, syngenic Lewis rats were randomized into cell transplantation (n=80) and control groups (n=72). SCs were isolated from sciatic nerves, and 5×10(6) cells were intramyocardially injected into the infarct region. Expression levels of myocardial nerve growth factor, vascular endothelial growth factor, growth-associated protein 43, connexin 43, and laminin in the SC group were significantly higher than control at 7 and 14 days after cell transplantation. Immunohistochemical staining illustrated increases in sympathetic and parasympathetic nerves in both groups. However, SC transplantation significantly increased the parasympathetic/sympathetic ratio at 14 days after cell injection. Dynamic electrocardiography and programmed electric stimulation were also performed. The SCs significantly decreased the low-/high-frequency ratio and arrhythmia score of programmed electric stimulation-induced ventricular arrhythmia at 2 weeks after cell injection. However, SCs did not restore heart function.


CONCLUSIONS
Transplanted SCs in the infarcted myocardium secrete multiple biological molecules, which alter the ratio of parasympathetic/sympathetic nerve density to normalize irritable myocardium. SC transplantation might be a novel cell-based antiarrhythmic therapy following MI.
Zhang
Hao
H
Department of Surgery, Cardiovascular Institute, Fu Wai Heart Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Yuan
Xin
X
Jin
Pei-feng
PF
Hou
Jian-feng
JF
Wang
Wei
W
Wei
Ying-jie
YJ
Hu
Shengshou
S
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000378:metabolism / Q000628:therapy; D018031:Connexin 43 / Q000378:metabolism; D022062:Electrophysiologic Techniques, Cardiac; D055724:Electrophysiological Phenomena; D019922:GAP-43 Protein; D006801:Humans; D008297:Male; D009124:Muscle Proteins / Q000378:metabolism*; D009203:Myocardial Infarction / Q000378:metabolism / Q000628:therapy*; D020932:Nerve Growth Factor / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D012583:Schwann Cells / Q000166:cytology / Q000378:metabolism / Q000637:transplantation*; D012584:Sciatic Nerve / Q000166:cytology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D018031:Connexin 43; D019922:GAP-43 Protein; D009124:Muscle Proteins; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D020932:Nerve Growth Factor