Extracardiac to coronary anastomoses support regional left ventricular function in dogs.
Intramyocardial implantation of a systemic artery [the internal mammary artery (IMA)] causes angiogenesis, with formation of systemic to coronary anastomoses. In dogs, we assessed the magnitude of IMA-derived nutritive flow and determined its influence on regional contraction. We also sought to determine whether acidic fibroblast growth factor (FGF), an angiogenic peptide, could enhance myocardial neovascularization. Ameroid constrictors and hydraulic balloon occluders were placed on the left anterior descending coronary artery (LAD) of 23 dogs, and the left IMA was implanted in the LAD territory. Dogs were randomized to receive continuous infusions of acidic FGF with heparin, heparin alone, or placebo directly into the IMA for 8 wk. Regional myocardial blood flow was assessed in the conscious state 3 days and 8 wk after operation. Left ventricular function was determined in the anesthetized state at the 8-wk conclusion of treatment. In all dogs, IMA occlusion reduced mean maximal LAD zone perfusion by 28% (P < 0.001), without influencing regional contraction. When IMA occlusion was superimposed on left circumflex coronary artery (LCX) occlusion, LAD zone perfusion declined by 34% (relative to LCX occlusion alone), significantly impairing regional contraction. Treatment with either acidic FGF plus heparin or heparin alone improved IMA-derived collateral flow; however, addition of acidic FGF to heparin afforded no additional advantage over heparin by itself. We conclude that acidic FGF did not enhance myocardial angiogenesis in this model. IMA-derived collateral flow has significant functional importance; however, it is evident in the dog only when other sources of collateral flow are compromised.
Unger
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EF
Laboratory of Experimental Physiology and Pharmacology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892.
Shou
M
M
Sheffield
C D
CD
Hodge
E
E
Jaye
M
M
Epstein
S E
SE
D000714:Anastomosis, Surgical; D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects; D003331:Coronary Vessels / Q000502:physiology*; D004285:Dogs; D005260:Female; D016220:Fibroblast Growth Factor 1 / Q000494:pharmacology; D006439:Hemodynamics; D006493:Heparin / Q000494:pharmacology; D008297:Male; D008323:Mammary Arteries / Q000637:transplantation*; D012039:Regional Blood Flow / Q000187:drug effects; D016277:Ventricular Function, Left
D016220:Fibroblast Growth Factor 1; D006493:Heparin