Effect of endothelial integrity, transmural pressure, and time on the intimal-medial uptake of serum 125I-albumin and 125I-LDL in an in vitro porcine arterial organ-support system.

Abstract

This report describes a new in vitro, metabolically supported, Sinclair Research Farm minipig aortic preparation in which the intimal-medial uptakes (M, mg.cm-2 of intimal surface) of porcine 125I-albumin and normocholesterolemic (nonoxidized) porcine 125I-low density lipoprotein (LDL) from a stirred, autogenous serum (containing a 125I-protein concentration of c0, mg.cm-3 at 37 degrees C and pH 7.4) were studied as functions of transmural pressure (0 < or = P < or = 150 mm Hg), time (30 < or = t < or = 120 minutes), and endothelial integrity. The following new observations were made: 1) The normalized transendothelial uptakes (M/c0, cm) of both albumin and LDL across normal intact aortic endothelial surfaces were insensitive to P. This indicated that these macromolecular solutes were not readily convected across the normal aortic endothelial surface despite increasing P. 2) However, the associated transendothelial M/c0 versus t relations for the normal intact surfaces were shown to increase monotonically with t in a manner consistent with a simple diffusive transport across a large surface barrier into the subjacent media, either with (Cases 2A and 2B) or without (Case 1) an associated transmural water convection. 3) The shapes of these temporal M/c0 curves of albumin and LDL were virtually the same; however, the magnitude of the albumin M/c0 curve was about sevenfold greater than that of LDL. 4) The M/c0 across the injured endothelial surface (Case 2C) not only increased monotonically with t but also increased significantly with P, indicating that in the absence of a normal endothelial surface, a very large convective component was added to the transport processes across the exposed aortic endothelial basement membrane and internal elastica. We conclude that: 1) the normal porcine aortic endothelial surface can provide a virtually complete barrier to the transendothelial convective transport of both albumin and LDL, 2) the diffusive barrier of the normal endothelial surface to LDL was sevenfold greater than that to albumin, 3) loss of the endothelial cell layer was associated with a threefold increase in the (P = 0) diffusive intimal-medial uptake of serum albumin in contrast to an eightfold increase in the pressurized (P = 150 mm Hg) combined diffusive-convective intimal-medial albumin uptake in the same vessel.