The Coronary Collateral Circulation in Man

Christian      Seiler

Abstract

Well developed coronary collateral arteries in patients with coronary artery disease (CAD) mitigate myocardial infarcts with less ventricular aneurysm formation and improved ventricular function, they reduce future cardiovascular events, and improve survival. Myocardial infarct size is a product of coronary artery occlusion time, area at risk for infarction and the inverse of collateral supply. Collateral arteries preventing myocardial ischemia during brief vascular occlusion are present in 1/3 of patients with CAD. Collateral flow sufficient to prevent myocardial ischemia during coronary occlusion amounts to ≥25% of the normal flow through the open vessel. Among individuals without relevant coronary stenoses, there are preformed collateral arteries preventing myocardial ischemia in 20-25%. Coronary collateral flow can be assessed only during vascular occlusion of the collateral-receiving artery. Presently, the gold standard for clinical coronary collateral assessment is the measurement of intracoronary occlusive pressure- or velocity- derived collateral flow index which expresses collateral as a fraction of flow during vessel patency. Clinical variables predicting the development of collateral arteries are the hemodynamic severity of coronary stenoses and the duration of myocardial ischemic symptoms. One fifth to one third of patients with CAD cannot be revascularized by percutaneous coronary intervention or coronary artery bypass grafting; therapeutic promotion of collateral growth appears to be a valuable treatment strategy in those patients. Promotion of collateral growth should aim at inducing the development of large conductive collateral arteries (i.e. arteriogenesis) and not so much the sprouting of capillary like vessels (i.e. angiogenesis). So far, the largest, controlled clinical angiogenesis trials on the efficacy of VEGF and basic FGF have been negative with regard to treadmill exercise time and myocardial scintigraphic data. Large conductive collateral arteries (i.e. arteriogenesis) appear to be effectively promoted via the activation of monocytes / macrophages, which release VEGF, FGF, tumor necrosis factor alpha, granulocyte colony stimulating factors and other growth and remodelling-associated factors.

Keywords: Coronary circulation, collateral circulation, arteriogenesis, angiogenesis