title: Catheter-based intramyocardial delivery (NavX) of adenovirus achieves safe and accurate gene transfer in pigs.
abstract: BACKGROUND
  Hepatocyte growth factor (HGF) is one of the major angiogenic factors being studied for the treatment of ischemic heart diseases. Our previous study demonstrated adenovirus-HGF was effective in myocardial ischemia models. The first clinical safety study showed a positive effect in patients with severe and diffused triple coronary disease.
  
  
  METHODS
  12 Pigs were randomized (1:1) to receive HGF, which was administered as five injections into the infarcted myocardium, or saline (control group). The injections were guided by EnSite NavX left ventricular electroanatomical mapping.
  
  
  RESULTS
  The catheter-based injections caused no pericardial effusion, malignant arrhythmia or death. During mapping and injection, alanine aminotransferase, aspartate aminotransferase, blood urea nitrogen, serum creatinine and creatine kinase-MB levels have no significant increase as compared to those before and after the injection in HGF group(P>0.05). HGF group has high HGF expression with Western blot, less myocardial infarct sizes by electroanatomical mapping (HGF group versus after saline group, 5.28 ± 0.55 cm(2) versus 9.06 ± 1.06 cm(2), P<0.01), better cardiac function with Gated-Single Photon Emission Computed Tomography compared with those in saline group. Histological, strongly increased lectin-positive microvessels and microvessel density were found in the myocardial ischemic regions in HGF group.
  
  
  CONCLUSIONS
  Intramyocardial injection guided by NavX system provides a method of feasible and safe percutaneous gene transfer to myocardial infarct regions.
authors.affiliation: Department of Cardiology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, The People's Republic of China.
authors.forename: Bo
authors.initials: B
authors.lastname: Chen
authors.forename: Zhengxian
authors.initials: Z
authors.lastname: Tao
authors.forename: Yingming
authors.initials: Y
authors.lastname: Zhao
authors.forename: Hongwu
authors.initials: H
authors.lastname: Chen
authors.forename: Yonghong
authors.initials: Y
authors.lastname: Yong
authors.forename: Xiang
authors.initials: X
authors.lastname: Liu
authors.forename: Hua
authors.initials: H
authors.lastname: Wang
authors.forename: Zuze
authors.initials: Z
authors.lastname: Wu
authors.forename: Zhijian
authors.initials: Z
authors.lastname: Yang
authors.forename: Li
authors.initials: L
authors.lastname: Yuan
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D002404:Catheterization; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors; D057809:HEK293 Cells; D006352:Heart Ventricles / Q000473:pathology; D017228:Hepatocyte Growth Factor / Q000235:genetics*; D006801:Humans; D008297:Male; D017202:Myocardial Ischemia / Q000473:pathology; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D011897:Random Allocation; D015203:Reproducibility of Results; D013552:Swine; D013556:Swine, Miniature; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods
chemical_list: D017228:Hepatocyte Growth Factor