The work in this grant application attempts to study the structure and function of the coronary microvasculature. The investigator hopes to solidify observations of how microbubbles used in myocardial contrast echo interact with endothelial cells and endothelial cell matrix and thus may act as markers of normal and disrupted endothelial cell. Secondly, the investigator also plans to apply the same technology, myocardial contrast echocardiography, to ex vivo and in vivo models of vascular function. The ultimate goal of this proposal is to develop techniques which will allow the investigator to gain pathophysiologic insights into pre-clinical endothelial function/dysfunction and angiogenesis in the intact animal. Although ischemic heart disease has many effects on the coronary microvasculature, this investigator will examine two aspects. First, based on her earlier observation that albumin coated, air-filled microbubbles (which are used in myocardial contrast echocardiography) interact with endothelial cells and the investigator will attempt to quantify the specific determinants of this interaction in a hope that it is a marker of vascular endothelial function. Secondly, the investigator will study the microvascular response to ischemia in the form of angiogenesis and collateral vessel development. Both of these processes have been difficult to study directly in vivo and the development of myocardial contrast echocardiography may enable real time examination of the coronary microvasculature. Thus, the two specific aims of this proposal are 1. to characterize sites and mechanism of microbubble-endothelial cell interaction using cell culture and optical imaging techniques and to use these findings to echocardiographically study endothelial function in ex vivo and in vivo animal models; and 2. to develop a new echocardiographic approach to measuring microvascular blood volume and then to use it for serial non-invasive examination of the distribution, natural history, and flow reserve of collateral vessels induced by specific fibroblast growth factor.
