The collateral circulation of the heart

Abstract

The coronary arteries have been regarded as end arteries for decades. However, there are functionally relevant anastomotic vessels, known as collateral arteries, which interconnect epicardial coronary arteries. These vessels provide an alternative source of blood supply to the myocardium in cases of occlusive coronary artery disease. The relevance of these collateral arteries is a matter of ongoing debate, but increasing evidence indicates a relevant protective role in patients with coronary artery disease. The collateral circulation can be assessed by different methods; the gold standard involves intracoronary pressure measurements. While the first clinical trials to therapeutically induce growth of collateral arteries have been unavailing, recent pilot studies using external counterpulsation or growth factors such as granulocyte colony stimulating factor (G-CSF) have shown promising results.

Figure 1

Schematic drawing of the coronary artery circulation with (left panel) and without (right panel) interarterial anastomoses between the right coronary artery and the occluded left anterior descending artery (LAD; occluded beyond the third diagonal branch). The gray area indicates the area at risk for myocardial infarction in case of the LAD occlusion and in the absence of collaterals (corresponding to the infarct size in the example on the right side). (Illustration by Anne Wadmore, Medical Illustrations Ltd, London, UK).

Figure 2

Mechanism of induction of collateral growth (arteriogenesis). (1) Endothelium senses shear stress via Ca+ channels, transduction via glycocalyx and cytoskeleton. (2) Actin-binding Rho-activating protein (ABRA) and early growth response protein 1 (EDGR1) genes are upregulated. (3) Activated endothelium expresses adhesion molecules such as intercellular adhesion molecule (ICAM) and growth factors such as monocyte chemoattractant protein 1 (MCP1) as well as NO. (4) Circulating monocytes bind their macrophage 1 antigen (Mac-1) receptors to ICAM. (5) Monocytes differentiate into macrophages and secrete additional growth factors and chemoattractants, stimulating proliferation of smooth muscle and endothelial cells. (Illustration by Anne Wadmore, Medical Illustrations Ltd).

Figure 3

Forest plot illustrating the results of a meta-analysis of all studies that have assessed the association between the degree of collateralization and mortality[13]. 95% CI, 95% confidence interval; CCC, coronary collateral circulation; RR, relative risk.