Ischemia-Induced Coronary Collateral Angiogenesis

Chronic myocardial ischemia is accompanied by growth of interarterial anastomoses in the coronary circulation (1, 2). These anastomoses, termed coronary collaterals, allow alternate sources of perfusion to supply ischemic myocardium and protect myocardium from reversible and irreversible tissue injury. Although the development of the collateral circulation in response to chronic coronary artery constriction/occlusion has been described (1–5), the mechanisms of and triggers for vascular growth are, at best, poorly understood. A plethora of mitogenic cytokines and growth factors have been implicated as initiators of angiogenesis, but the temporal relationships amongst intensity of ischemia, coronary collateral development/perfusion and growth factor production have not been systematically studied. The purpose of the present investigation was to characterize the time-course of development of the coronary collateral circulation in response to chronic myocardial ischemia in vivo and determine if expression of specific growth factors, including vascular endothelial growth factor (VEGF) occurs in a well-defined temporal relation. A microdialysis chamber implanted into the myocardium allowed daily sampling of interstitial fluid for subsequent assessment of mitogenic activity in vitro.