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.
Division of Cardiovascular Medicine, Stanford University Medical Center, Stanford, California 94305, USA. wfearon@stanford.edu
William F
WF
Fearon
Fumiaki
F
Ikeno
Lynn R
LR
Bailey
Bonnie L
BL
Hiatt
Niall A
NA
Herity
Andrew J
AJ
Carter
Peter J
PJ
Fitzgerald
Mehrdad
M
Rezaee
Alan C
AC
Yeung
Paul G
PG
Yock
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