Heparin and angiogenic therapy.

Collateral circulation is an alternative source of blood supply to the myocardium if this is jeopardized by failure of the original vessel to provide adequate flow. Gradual occlusion, or a high grade stenosis of the coronary arteries, is frequently associated with collateral development in patients with coronary artery disease. Although the existence of collateral circulation in such patients is associated with improved clinical outcomes, the net effect is inadequate to compensate for the flow deficit in the native coronary arteries. Why the flow reserve through collateral circulation is limited to half of that of normal coronary circulation is not clear. However, several pieces of evidence indicate that it is possible to promote collateral development intentionally to alleviate myocardial ischaemia under stressed conditions. Angiogenic therapy is defined as the intervention used to treat or prevent pathological clinical situations characterized by local hypovascularity by stimulating or inducing collateral development. Until our clinical study, there had been no reports, except for an intense year-long exercise training programme, showing enhanced collateral development through some kind of intervention. We have demonstrated for the first time that the combination of heparin and exercise-induced myocardial ischaemia enhances collateral function and growth in patients with stable effort angina. Recently, angiogenic growth factors such as basic fibroblast growth factor and vascular endothelial growth factor were successfully used to stimulate cardiac angiogenesis to improve collateral circulation not only in various animal models but also in clinical settings. Heparin was discovered by McLean in 1916. Since then, many investigators have contributed to elucidate the basic and clinical properties of heparin. It has recently been recognized that heparin potentiates the activity of growth factors. This property of heparin