Endothelium and Compound Transfer

Abstract

One approach to the study of cell function in situ and to the quantitative phenotyping required for functional genomics and genetic circuit analysis is the bolus injection—outflow detection—multiple indicator dilution (MID) method. The MID method is a tracer dilution method used to measure tissue volumes (Goresky 1963; Goresky et al. 1970; Chinard 1975; Bassingthwaighte and Goresky 1984; Dawson et al. 1989, 1992), tissue composition (Dawson et al. 1989, 1992; Roerig et al. 1999), transcapillary transport parameters (Goresky et al. 1970; Bassingthwaighte 1974; Harris et al. 1978; Bassingthwaighte and Goresky 1984; Harris et al. 1987; Dawson et al. 1989; Audi et al. 1996 a, 2000; Linehan et al. 1998), enzyme or receptor binding (Maolli et al. 1985; Dawson et al. 1989; Linehan et al. 1998; Roerig et al. 2000), and enzyme kinetics (Goresky et al. 1983, 1993; Riggs et al. 1988; Dawson et al. 1989; Linehan et al. 1998; Audi et al. 2000) within an organ. The focus of this chapter will be on the application of the MID method to measurement of endothelial transport and metabolism, particularly in the lungs. In comparison to other organs, lung tissue is disproportionately comprised of endothelial cells, and the lungs contain a large fraction (nearly half) of the vascular endothelium of the entire body. Although endothelial functions can be organ-specific, the lung serves as a good model for demonstrating general principles involved in the application of the method.