Mc. Oz et al., ATTENUATION OF MICROVASCULAR PERMEABILITY DYSFUNCTION IN POSTISCHEMICSTRIATED-MUSCLE BY HYDROXYETHYL STARCH, Microvascular research, 50(1), 1995, pp. 71-79
We examined the effect of hydroxyethyl starch macromolecule (HES-Pz) p
retreatment on microvascular transport of macromolecules in ischemia-r
eperfusion injury. The rat cremaster was splayed, placed in a Lucite i
ntravital chamber, and suffused with bicarbonate buffer. The clearance
of fluorescein isothiocyanate dextran 150 (FITC-Dx 150) was measured
as an index of microvascular transport. After determination of baselin
e data, the muscle was made ischemic for 4 hr by clamping the vascular
pedicle and subsequently reperfused for 2 hr. In control animals not
subjected to ischemia, clearance of FITC-Dx 150 remained constant thro
ughout the experimental 7-hr period. In saline-treated animals, ischem
ia-reperfusion increased the clearance of FITC-Dx 150 from 1.8 +/- 0.3
to 9.7 +/- 1.0 mu l/15 min/g by the end of the reperfusion period. Pr
etreatment with HES-Pz, at a concentration of 6% in a volume of saline
equivalent to 10% of blood volume, significantly attenuated the micro
vascular dysfunction produced by ischemia-reperfusion. The mean ratio
of postischemic to baseline clearance of FITC-Dx 150 was 1.28 +/- 0.07
(mean +/- SE) for samples taken from the 30th to the 120th min of rep
erfusion at 15 intervals. Our data support a beneficial effect of HES-
Pz on microvascular transport of macromolecules. The role of leukocyte
-endothelium adhesion as an underlying mechanism explaining these resu
lts was studied by evaluating the effect of HES-Pz on the ability of t
hrombin-stimulated human umbilical vein endothelial cells (HUVECs) to
bind neutrophils. These experiments demonstrated that thrombin-treated
HUVECS bound 229% more indium-111-labeled neutrophils than did simila
rly stimulated HUVECS treated with HES-Pz (P < 0.05). We propose that
HES-Pz may act by sealing and restoring microvascular integrity and by
blunting the increased adhesiveness of stimulated endothelial cells f
or neutrophils. (C) 1995 Academic Press, Inc.