Extravascular distribution of low-density lipoprotein and dextran in a high-permeability state

Abstract

Previous studies from this laboratory indicated that in the early phase of a high-permeability state, low-density lipoprotein (LDL) crosses the microvascular barrier by porous pathways ( J. C. Rutledge, F. E. Curry, J. F. Lenz, and P. Davis, 1989, Circ. Res. 1990 ; 66, 486–495). To determine the extravascular distribution of LDL (3,500,000 MW) and a smaller reference macromolecule [20,000 MW dextran (D20)] image processing techniques were employed, and extravascular accumulation of solutes from different microvessels was compared to quantitative fluorescence microscopy. Frog mesenteric venular microvessels ( n = 8) were cannulated and perfused with fluorescent-labeled LDL and D20 and extravascular distribution of both solutes was imaged at control and after permeability was increased with the calcium ionophore ionomycin (5 μ M). At the peak increase in apparent permeability (2–4 min after ionophore), the processed images of the microvessels demonstrated that the extravascular distribution of fluorescent-labeled solute was not uniform and that D20 accumulated outside the microvessel wall in some areas where LDL did not accumulate. The patterns of extravascular accumulation of LDL and D20 in a high-permeability state imply a distribution of effective microvascular pore sizes and/or a distribution of resistances to solute flow in the pore or in the tissue surrounding the microvessel.