[Autologous sinoatrial node cells heterotopic transplantation for treating bradycardia: an experiment with dogs].
OBJECTIVE
To explore the feasibility of autografting sinoatrial nodal cells heterotopic transplantation to construct an ectopia pacemaker for treating bradycardia.


METHODS
Sixteen healthy adult dogs were randomly divided into 2 equal groups: graft group and control group. The sinoatrial node (SAN) of the dogs in the graft group was harvested and digested into cell suspension in vitro, then injected to the autogenic right ventricular wall adjacent to heart apex. Commensurable culture medium was injected to the same position with the dogs in control group. Two week later, all dogs underwent transcatheter ablation of His bundle to create a complete heart block model and an electrophysiology study was carried out. In order to investigate the change of rhythm, isoproterenol and atropine was injected respectively to dogs of the graft group. Two weeks later the dogs were killed with their hearts taken out. Immunofluorescence histochemistry was used to investigate the survival of grafted cells and gap junction formed between grafted cells and ventricular myocytes. RESULTS The isolated cells from SAN retained active and beating. After ablation, the heart rate of the dogs of the graft group was (91 +/- 14) bpm, significantly higher than that of the control group, [(49 +/- 11) bpm, t = 6. 672, P < 0.01], and electrocardiography showed that these ventricular rhythms originated from the cell transplant sites. After the injection of isoproterenol the ventricular rate of the graft group was (118 +/- 15) bpm, significantly higher than that before the injection, (95 +/- 11) bpm, t = 3.491, P < 0.01), however, after the injection of atropine, the heart rate of the graft group was (101 +/- 17) bpm, not significantly different from that before the injection, [(95 +/- 11) bpm, t = 0.838, P > 0.05]. Immunofluorescence staining showed that the grafted autografting sinoatrial nodal cells all survived and that there was connexin-43 expression among the cells.


CONCLUSIONS
Transplantation of autologous SAN cells into the right ventricular wall can boost the ventricular rhythm which is sensitive to isoproterenol but not to atropine. Grafted SAN cells can form gap junctions with adjacent myocytes.
Zhang
Hao
H
Department of Cardiothoracic Surgery, Changhai Hospital, Second Military Medical University, Shanghai, China.
Yao
Ying-long
YL
Duan
Lian
L
Song
Zhi-gang
ZG
Zou
Yi-qing
YQ
Zong
Gang-jun
GJ
Xu
Zhi-yun
ZY
D000818:Animals; D001285:Atropine / Q000008:administration & dosage / Q000494:pharmacology; D001919:Bradycardia / Q000503:physiopathology / Q000601:surgery*; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000494:pharmacology; D002470:Cell Survival; D017690:Cell Transplantation / Q000379:methods*; D018031:Connexin 43 / Q000032:analysis; D004195:Disease Models, Animal; D004285:Dogs; D004562:Electrocardiography; D005455:Fluorescent Antibody Technique; D006339:Heart Rate / Q000187:drug effects; D007545:Isoproterenol / Q000008:administration & dosage / Q000494:pharmacology; D011897:Random Allocation; D012849:Sinoatrial Node / Q000737:chemistry / Q000166:cytology*; D014182:Transplantation, Autologous
D001993:Bronchodilator Agents; D018031:Connexin 43; D001285:Atropine; D007545:Isoproterenol