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Department of Bioengineering, University of Washington, Seattle, Washington 98195
Submitted 11 July 2002 ; accepted in final form 5 May 2003
Osmotic transient responses in organ weight after changes in perfusate
osmolarity have implied steric hindrance to small-molecule transcapillary
exchange, but tracer methods do not. We obtained osmotic weight transient data
in isolated, Ringer-perfused rabbit hearts with NaCl, urea, glucose, sucrose,
raffinose, inulin, and albumin and analyzed the data with a new anatomically
and physicochemically based model accounting for 1) transendothelial
water flux, 2) two sizes of porous passages across the capillary
wall, 3) axial intracapillary concentration gradients, and 4) water
fluxes between myocytes and interstitium. During steady-state conditions
28% of the transcapillary water flux going to form lymph was through the
endothelial cell membranes [capillary hydraulic conductivity
(Lp) = 1.8 ± 0.6 x
10–8 cm · s–1
· mmHg–1], presumably mainly through
aquaporin channels. The interendothelial clefts (with Lp =
4.4 ± 1.3 x 10–8 cm ·
s–1 · mmHg–1)
account for 67% of the water flux; clefts are so wide (equivalent pore radius
was 7 ± 0.2 nm, covering 0.02% of the capillary surface area) that
there is no apparent hindrance for molecules as large as raffinose. Infrequent
large pores account for the remaining 5% of the flux. During osmotic
transients due to 30 mM increases in concentrations of small solutes, the
transendothelial water flux was in the opposite direction and almost 800 times
as large and was entirely transendothelial because no solute gradient forms
across the pores. During albumin transients, gradients persisted for long
times because albumin does not permeate small pores; the water fluxes per
milliosmolar osmolarity change were 200 times larger than steady-state water
flux. The analysis completely reconciles data from osmotic transient, tracer
dilution, and lymph sampling techniques.
capillary permeability; reflection coefficient; transport modeling; microcirculation; isolated rabbit heart; porous transport
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