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Catheter-based intramyocardial delivery (NavX) of adenovirus achieves safe and accurate gene transfer in pigs.
- Source :
-
PloS one [PLoS One] 2013; Vol. 8 (1), pp. e53007. Date of Electronic Publication: 2013 Jan 03. - Publication Year :
- 2013
-
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.<br />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.<br />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.<br />Conclusion: Intramyocardial injection guided by NavX system provides a method of feasible and safe percutaneous gene transfer to myocardial infarct regions.
- Subjects :
- Animals
Catheterization
Genetic Therapy methods
Genetic Vectors
HEK293 Cells
Heart Ventricles pathology
Humans
Male
Myocardial Ischemia pathology
Myocardium pathology
Random Allocation
Reproducibility of Results
Swine
Swine, Miniature
Tomography, Emission-Computed, Single-Photon methods
Adenoviridae genetics
Gene Transfer Techniques
Hepatocyte Growth Factor genetics
Myocardium metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 8
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 23301013
- Full Text :
- https://doi.org/10.1371/journal.pone.0053007