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.

Abstract

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<O.OOS). 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<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. (Circulation 1990;82:1449-1466

Direct Left Ventricle-to-Coronary Artery Stent Restores Perfusion to Chronic Ischemic Swine Myocardium

“…The release of angiogenic factors comes after myocardial injury, ischemia, inflammation, mechanical stress, and myocardial hemorrhage, all of which likely occur with VSTENT placement [Kantor 1999;Simons 2004]. A highly regulated sequence of events, from migration of capillary endothelial cells to lumen formation to finally formation of microvascular networks, typically takes at least 2 weeks to occur with measurable results [Unger 1990;Kohmoto 1996]. This corresponds very closely to our results, which demonstrate a marked increase in perfusion at 3 weeks.…”

Extracardiac coronary arterial anastomoses

“…In a later study, they concluded that the extracardiac anastomoses were capable of providing significant support for the improvement of left ventricular function (Unger et al, 1993). This research highlights the therapeutic possibilities for controlled vascular development and angiogenesis (Unger et al, 1990). Such treatment, potentially, could both inhibit pathological vascular growth, and enhance the development of collateral arteries subsequent to myocardial ischemia (Kass et al, 1992).…”

Salvage of Infarcted Myocardium by Angiogenic Action of Basic Fibroblast Growth Factor

“…Whether the capillaries and arterioles that appear in canine cardiac tissue treated with FGF function as well as existing vessels is not clear; however, newly created arterioles and capillaries can function as perfusing vessels (16). The beneficial function of coronary collateral vessels in salvaging the myocardium from ischemia has been discussed in experimental animal models of coronary stenosis or obstruction (4) and in clinical studies of ischemic heart disease (2,4,(17)(18)(19)(20).…”