Three catheter-based strategies for cardiac delivery of therapeutic gelatin microspheres.
Gelatin hydrogel microspheres (GHMs) have been reported as novel non-viral vectors for gene or protein delivery (GHM therapy). However, the components of an effective catheter-based delivery strategy for GHM therapy are unknown. We evaluated the effectiveness of three catheter-based strategies for cardiac GHM therapy: (1) antegrade injection (AI) via coronary arteries; (2) retrograde injection (RI) via coronary veins; and (3) direct myocardial injection (DI) via the coronary sinus. AI distributed microspheres homogeneously throughout the target area with 73+/-11% retention. RI scattered microspheres non-homogenously with 22+/-8% retention. DI distributed microspheres in the needle-advanced area with 47+/-14% retention. However, despite high efficiency, AI did not show biological effects of inducing angiogenesis from basic fibroblast growth factor bound to GHMs. Furthermore, focal micro-infarctions, owing to micro-embolism of aggregated GHMs into small coronary arterioles, were detected in the AI group. Conversely, only RI and DI groups displayed increased coronary flow reserve. DI groups also demonstrated increased capillary density. These results suggest that RI and DI are effective for cardiac GHM therapy, while AI appears inappropriate owing to the risk of focal infarctions.
Hoshino
K
K
Cardiology Laboratory for Integrative Physiology and Imaging, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA. kozo@kyoto-u.ac.jp
Kimura
T
T
De Grand
A M
AM
Yoneyama
R
R
Kawase
Y
Y
Houser
S
S
Ly
H Q
HQ
Kushibiki
T
T
Furukawa
Y
Y
Ono
K
K
Tabata
Y
Y
Frangioni
J V
JV
Kita
T
T
Hajjar
R J
RJ
Hayase
M
M
D000818:Animals; D002404:Catheterization; D003326:Coronary Circulation; D003331:Coronary Vessels; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage* / Q000378:metabolism; D005780:Gelatin; D015316:Genetic Therapy / Q000379:methods; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D007267:Injections / Q000009:adverse effects / Q000379:methods; D008863:Microspheres; D023421:Models, Animal; D009203:Myocardial Infarction / Q000209:etiology; D009206:Myocardium / Q000378:metabolism*; D018919:Neovascularization, Physiologic; D011994:Recombinant Proteins / Q000008:administration & dosage; D012039:Regional Blood Flow; D033581:Stem Cell Transplantation / Q000379:methods; D013552:Swine
D011994:Recombinant Proteins; D016222:Fibroblast Growth Factor 2; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D005780:Gelatin