MISE AU POINT D＇UNE TECHNIQUE D＇ADMINISTRATION IN VIVO DES VECTEURS GENETIQUES DANS LE MUSCLE CARDIAQUE

摘要

Objective In order to improve the in vivo gene transfer into the heart muscle, we have de-signed α ECG-synchronized microinjection system that allows sequential gene delivery to the myocardium.Methods A cannula was introduced into the right carotid artery of the Wistar rat under general anesthesia. With the ECG-synchronized injection during diastole, the genetic vector (Ad CMV lacZ ) infusion was per-formed with various concentrations( 10^7-10^10pfu ) and different frequency ( the ratio of heart beats per injec-tion from 1 : 1 to 4 : 1 ). The hearts of the rats were removed after 7 days for histological examination. Results Best results were obtained with a total vector amount of 10^9 pfu and a good ratio 3 : 1 between heart frequency and injection frequency. The transfection efficiency was increased by use of vasodilators and by an increase of vascular permeability. No signs of myocardial ischemia or ventricular arrythmia were observed. Conclusion We have established a novel and safe method for in vivo gene transfer into the heart. Transgene expression suggests that this method may be useful technique to study cardiac function of treat cardiac diseases by means of gene therapy.