Delivery strategies to achieve therapeutic myocardial angiogenesis.
The use of recombinant genes or growth factors to enhance myocardial collateral blood vessel function may represent a new approach to the treatment of cardiovascular disease. Proof of concept has been demonstrated in animal models of myocardial ischemia, and clinical trials are underway. Currently, it is unknown which is the safest and most effective delivery strategy to induce clinically important therapeutic angiogenic responses in ischemic myocardium. Most strategies for transcatheter delivery of angiogenic factors have used an intracoronary route, which may have limitations because of imprecise localization of genes or proteins and systemic delivery to noncardiac tissue. The effect of direct intraoperative intramyocardial injection of angiogenic factors on collateral function has been reported in experimental models, and angiogenesis is being studied after direct intramyocardial injection of angiogenic peptides or plasmid vectors during open heart surgery in patients. Catheter-based transendocardial injection of angiogenic factors may provide equivalent benefit without the need for surgery. Intrapericardial delivery of angiogenic factors may offer a theoretical advantage of prolonged exposure of either coronary or myocardial tissue to the administered drug as result of a reservoir function of the pericardium. In this article, we review the different modes of administration for therapeutic myocardial angiogenesis therapy.
Kornowski
R
R
Cardiovascular Research Foundation, Washington Hospital Center, Washington DC 20010, USA. rxk3@mhg.edu
Fuchs
S
S
Leon
M B
MB
Epstein
S E
SE
D000818:Animals; D002318:Cardiovascular Diseases / Q000188:drug therapy* / Q000503:physiopathology; D003097:Collateral Circulation; D003331:Coronary Vessels / Q000187:drug effects / Q000503:physiopathology*; D016228:Endothelial Growth Factors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008222:Lymphokines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D017202:Myocardial Ischemia / Q000188:drug therapy*; D018919:Neovascularization, Physiologic; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D016222:Fibroblast Growth Factor 2