[Transfecting rat heart with human pacemaker gene in vivo to create a biological pacemaker].
OBJECTIVE
To test the ability and safety of injecting the hHCN gene into the ventricle of intact rats to create a novel biological pacemaker and to explore the duration of the hHCN over-expression in vivo.


METHODS
Adenoviral constructs incorporating hHCN4 and green fluorescent protein (GFP) were subepicardially injected into the rats' left ventricular wall in situ (n = 10). Control group was injected with adenoviral constructs of GFP alone (n = 10). ECGs were recorded every day within the initial three days after operation. Up to seven days after injection, all rats were anesthetized and subjected to cervical vagal trunks stimulation to permit the emergence of escape rhythm. Then pace-mapping was performed by the hand-hold electrode. Finally, hearts were removed for histology and immunofluorescence study.


RESULTS
Ventricular arrhythmic events were not found during the first three days. During vagal stimulation, the rate of spontaneous rhythm in the hHCN4-injected group was significantly more rapid than that in the control group (69 bpm +/- 6 bpm vs 41 bpm +/- 10 bpm, P < 0.001). Pace-mapping confirmed the escape rhythm in the hHCN4-injected group was originated near the injection site. Immunofluorescence study showed the overexpression of hHCN4 on the site of injection. However, the duration of hHCN overexpression was no more than one month after injection.


CONCLUSIONS
The overexpression of hHCN4 provides ventricular escape rhythm with the physiologically acceptable rate. Long-term feasibility of this approach needs to be tested.
Zhong
You-min
YM
Cardiac Electrophysiology Laboratory, People's Hospital, Peking University, Beijing 100044, China.
Guo
Ji-hong
JH
Zhang
Ping
P
Li
Ji-wen
JW
Liu
Yuan-wei
YW
Zhou
Chun-yan
CY
Zhang
You-yi
YY
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D002304:Cardiac Pacing, Artificial; D054815:Cyclic Nucleotide-Gated Cation Channels / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D004562:Electrocardiography; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006321:Heart / Q000502:physiology*; D006801:Humans; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D008297:Male; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D009206:Myocardium / Q000378:metabolism*; D015221:Potassium Channels; D021381:Protein Transport; D051381:Rats; D017207:Rats, Sprague-Dawley; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism
D054815:Cyclic Nucleotide-Gated Cation Channels; C119587:HCN4 protein, human; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D009124:Muscle Proteins; D015221:Potassium Channels; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins