Enhancing myocardial plasmid expression by retrograde coronary venous delivery.
Myocardial delivery of genes holds great promise for treating many heart diseases; however, the optimal delivery technique, which maximizes safety and efficacy, has not been established. Two delivery techniques were evaluated in swine; percutaneous retrograde coronary venous delivery (RCVD) and direct intramyocardial injection (IM). RCVD was performed in the anterior interventricular vein (AIV) with an end-hole occlusion balloon catheter. The plasmid gWiz, encoding beta-galactosidase (10 ml; 1 mg/ml), was injected using either manual high pressure (HP-RCVD; n = 5) or pressure wire-guided low pressure (LP-RCVD; n = 4). For the IM group (n = 4), beta-Gal plasmid (5 mg/ml) was injected at 10 sites (200 microl/site) in the anterior left ventricular wall. Animals were euthanized after 5 days. The percentage of beta-Gal expressing cells in the delivered region was higher in the HP-RCVD (0.26% +/- 0.05%) than the LP-RCVD (0.05% +/- 0.03%; P = 0.07) and IM groups (0.02% +/- 0.01%; P = 0.01). Myocardium from the HP-RCVD group contained 7- and 17-fold higher levels of beta-Gal activity than either LP-RCVD and IM groups, respectively (P = 0.05 for both). The results of this study confirm the safety and efficacy of RCVD for myocardial gene delivery.
Youssef
Eyas Al-Shaykh
EA
Krannert Institute of Cardiology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Zhang
Ping
P
Rogers
Pamela I
PI
Tremble
Patrice
P
Rokovich
Joe
J
Johnstone
Brian H
BH
March
Keith L
KL
Hou
Dongming
D
D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D003326:Coronary Circulation / Q000502:physiology*; D003331:Coronary Vessels / Q000378:metabolism* / Q000503:physiopathology*; D004195:Disease Models, Animal; D005260:Female; D006352:Heart Ventricles / Q000378:metabolism; D006801:Humans; D008297:Male; D008955:Models, Cardiovascular; D017202:Myocardial Ischemia / Q000378:metabolism / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D010957:Plasmids / Q000008:administration & dosage / Q000096:biosynthesis*; D013552:Swine; D001616:beta-Galactosidase / Q000378:metabolism
D001616:beta-Galactosidase