Creation of anastomoses between an extracardiac artery and the coronary circulation. Proof that myocardial angiogenesis occurs and can provide nutritional blood flow to the myocardium.
The purpose of this investigation was to determine whether blood vessels could develop de novo between an extracardiac artery and a collateral-dependent zone of the heart and to quantify the nutritive blood flow afforded by the new vessels. We also adapted the preparation so that angiogenically active agents could be chronically administered directly to the site of neovascularization in subsequent studies. To induce neovascularization between a systemic artery and the coronary circulation, the left internal mammary artery (IMA) was implanted in an intramyocardial tunnel in proximity to the left anterior descending coronary artery (LAD). A tube situated in the distal IMA connected to an implanted pump provided for continuous intra-arterial infusion at the site of angiogenesis. During the same procedure, an ameroid constrictor was placed on the proximal LAD, rendering its perfusion territory collateral dependent during a 2-3 week period. After 8 weeks, the functional capacity of the anastomoses established between the implanted IMA and the LAD territory was assessed by determining regional myocardial blood flow under basal conditions, during adenosine-induced vasodilatation, and during differential occlusions of the IMA and left circumflex coronary artery (LCCA). For all dogs, IMA occlusion decreased maximal LAD territory flow from 1.31 +/- 0.11 to 1.16 +/- 0.10 ml/min/g (p less than 0.005). Occlusion of the LCCA decreased LAD zone flow to 0.73 +/- 0.12 ml/min/g, whereas occlusion of the IMA in addition to the LCCA further decreased LAD zone flow to 0.42 +/- 0.11 ml/min/g (p less than 0.02). The IMA provided measurable nutritive blood flow in seven of 12 dogs, and in these dogs, the artery provided 30.0 +/- 2.5% of total LAD zone collateral conductance under conditions of maximal vasodilatation (range, 23-42%). We conclude that angiogenesis can occur between an implanted internal mammary artery and the native coronary circulation in dogs, providing modest nutritive blood flow to a collateral-dependent region. Further studies will be necessary to determine whether direct, local infusion of angiogenically active factors can enhance neovascularization and whether sufficient flow can be reliably supplied to make some variant of this approach clinically applicable.
Laboratory of Experimental Physiology and Pharmacology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892.
E F
EF
Unger
C D
CD
Sheffield
S E
SE
Epstein
D000824:Animal Nutritional Physiological Phenomena; D000818:Animals; D003097:Collateral Circulation; D003326:Coronary Circulation; D003331:Coronary Vessels / Q000502:physiology*; D004285:Dogs; D005260:Female; D006321:Heart / Q000502:physiology*; D006439:Hemodynamics; D008297:Male; D008323:Mammary Arteries / Q000502:physiology / Q000637:transplantation; D008955:Models, Cardiovascular; D009389:Neovascularization, Pathologic; D012039:Regional Blood Flow; D012212:Rheology