RECENT INSIGHTS INTO CORONARY COLLATERAL CIRCULATION

The functional significance of coronary collaterals in humans has been debated for many years. Correlations have now been made between the anatomic appearance of coronary collateral vessels visualized at the time of intracoronary thrombolytic therapy during the acute phase of myocardial infarction and the creatine kinase time-activity curve, infarct size, and aneurysm formation. These studies demonstrate a protective role of collaterals in hearts with coronary obstructive disease, showing smaller infarcts, less aneurysm formation, and improved ventricular function compared with patients in whom collaterals were not visualized. There is ample evidence that collaterals respond to myocardial ischemia by opening preexistent channels. When the cardiac myocyte is rendered ischemic, collaterals develop actively by growth with DNA replication and mitosis of endothelial and smooth muscle cells. Heparin-binding growth factors are present in the heart, but their biological activity is quiescent under normal physiological conditions. Once ischemia develops, these factors are activated and become available for receptor occupation, which may initiate angiogenesis after exposure to exogenous heparin. This characteristic of heparin to potentiate the mitogenic activity of acidic fibroblast growth factor has recently been used in the clinical setting as a possible therapeutic modality in patients with coronary artery disease. Patients performing 20 rounds of exercise serially after receiving intravenous injection of heparin showed significantly greater increases in exercise capacity and improvement of clinical symptoms compared with the control group who performed the same exercise without heparin. Further study of neovascularization may lead to a new therapeutic strategy for ischemic heart disease. Thus, recent basic and clinical investigations have elucidated the importance of the coronary collateral circulation for protection of compromised myocardium during severe coronary stenosis. A complete understanding of the precise mechanism of angiogenesis could lead to the development of new drugs capable of enhancing angiogenesis of collateral vessels more effectively in patients with coronary artery disease.