Evaluation of high-pressure retrograde coronary venous delivery of FGF-2 protein.
Delivery of angiogenic factors to ischemic myocardium remains a practical challenge. We evaluated the efficiency and efficacy of delivery of fibroblast growth factor-2 (FGF-2) protein via high-pressure retrograde injection into the anterior interventricular vein (AIV) in a porcine model of chronic myocardial ischemia. Labeled FGF-2 protein was delivered to the myocardium of three pigs via the AIV and the left anterior descending (LAD) coronary artery in three others. At 1 hr, the amount of protein in the left ventricle and the LAD region was quantified. Copper stents were implanted in the LAD of 25 pigs, resulting in chronic myocardial ischemia. At 4 weeks, microsphere-derived myocardial blood flow was assessed at rest and during pacing. In eight pigs (AIV FGF), FGF-2 protein (6 microg/kg) was delivered via high-pressure retrograde injection into the AIV. Six pigs (intracoronary FGF) received the same amount of FGF-2 by intracoronary delivery. Five pigs (AIV saline) received a placebo injection into the AIV and six pigs (control) served as controls. Four weeks later, myocardial blood flow was reassessed. At 1 hr, significantly more FGF remained in the left ventricle (1.3 vs. 0.82 microg; P < 0.04) and in the LAD region (1.2 vs. 0.64 microg; P = 0.03) after AIV compared to intracoronary delivery. Four weeks after treatment, resting LAD blood flow (normalized to right ventricular flow) improved slightly in the AIV FGF and intracoronary FGF arms (1.32-1.37 for both; P = 0.11), while it decreased significantly in the AIV saline (1.32-1.23; P = 0.02) and the control arms (1.32-1.19; P = 0.0004). Pacing LAD blood flow decreased significantly in the control arm (1.30-1.23; P < 0.05), but did not change significantly in the other three arms. High-pressure retrograde injection into the AIV may represent an efficient and effective means for delivering angiogenic factors to ischemic myocardium.
Fearon
William F
WF
Division of Cardiovascular Medicine, Stanford University Medical Center, Stanford, California 94305, USA. wfearon@stanford.edu
Ikeno
Fumiaki
F
Bailey
Lynn R
LR
Hiatt
Bonnie L
BL
Herity
Niall A
NA
Carter
Andrew J
AJ
Fitzgerald
Peter J
PJ
Rezaee
Mehrdad
M
Yeung
Alan C
AC
Yock
Paul G
PG
D000818:Animals; D003326:Coronary Circulation; D003331:Coronary Vessels; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D007269:Injections, Intra-Arterial; D007275:Injections, Intravenous; D008187:Lutetium; D017202:Myocardial Ischemia / Q000188:drug therapy*; D009206:Myocardium / Q000378:metabolism; D015607:Stents; D013552:Swine
D016222:Fibroblast Growth Factor 2; D008187:Lutetium