title: The feasibility and safety of transendocardial gene injection in canine using a multifunctional intracardiac echocardiography catheter.
abstract: BACKGROUND
  Transendocardial gene delivery may expose patients to the risk of pericardial perfusion due to excessive needle injections. This study investigated the feasibility and safety of transendocardial gene injection using a newly developed multifunctional intracardiac echocardiography catheter.
  
  
  METHODS
  This new system integrated intracardiac echocardiography, a retractable 29-G needle, and other accessories into a single catheter (10F) that could be delivered into the left ventricle via a retrograde aortic approach. In three canines, the catheter was used to inject 0.2 ml of Evan's blue; six canines received myocardial injections of plasmid containing the EGFP transgene. In addition, two canines received transendocardial injections of a pAdTrace-bFGF plasmid. All canines receiving gene delivery were sacrificed after 3 days. The hearts were harvested for gross, histological examination and gene expression assessment.
  
  
  RESULTS
  This catheter provided visual guidance for accurate needle-tip positioning within the target myocardium; the needle position was subsequently confirmed by microbubble infusion. No animal had pericardial effusion or sustained ventricular arrhythmia. Tissue staining showed well-demarcated margins within the target myocardium. In animals injected with pEGFP-N1, confocal microscopy demonstrated successful gene expression. In zones where pAdTrace-bFGF was injected, immunohistochemistry also showed positive staining. Compared to normal tissue (0.38±0.04), RT-PCR showed high levels of bFGF expression (0.63±0.02) in the target area (P<0.01).
  
  
  CONCLUSIONS
  Transendocardial gene injection using a multifunctional intracardiac echocardiography catheter is feasible and could improve procedure-related safety which may provide a new strategy for transgene delivery in future.
authors: Institute of Ultrasound Imaging, Chongqing Medical University, Department of Cardiology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, PR China.
authors: Rui
authors: R
authors: Guo
authors: Jun
authors: J
authors: Qian
authors: Ya
authors: Y
authors: Yang
authors: Dayan
authors: D
authors: Zhou
authors: Que
authors: Q
authors: Zhu
authors: Dichuan
authors: D
authors: Liu
authors: Changming
authors: C
authors: Deng
authors: Zhigang
authors: Z
authors: Wang
authors: Jing
authors: J
authors: Huang
mesh_terms: D000818:Animals; D006328:Cardiac Catheterization / Q000009:adverse effects / Q000379:methods*; D004285:Dogs; D004452:Echocardiography / Q000379:methods; D004699:Endocardium / Q000000981:diagnostic imaging* / Q000187:drug effects / Q000502:physiology*; D005240:Feasibility Studies; D005260:Female; D018014:Gene Transfer Techniques / Q000009:adverse effects; D008297:Male