Fructose-1,6-diphosphate or adenosine attenuate leukocyte adherence
and microvascular dysfunction in postischemic skeletal muscle.
Akimitsu, Tadafumi, Jacqueline A. White, Donna L. Carden, Dean C.
Gute, and Ronald J. Korthuis.
Department of Physiology and Biophysics, Louisiana State
University, School of Medicine in Shreveport, Shreveport, LA
71130
APStracts 2:0218H, 1995.
The purpose of this study was to determine whether fructose-1,6
-diphosphate (FDP) or adenosine (ADO), administered at the onset of
reperfusion, would prevent I/R-induced leukocyte adherence and
microvascular dysfunction in skeletal muscle. Changes in vascular
permeability and tissue neutrophil content were assessed by
measurement of the solvent drag reflection coefficient ([sigma]) for
total plasma proteins and muscle myeloperoxidase (MPO) activity,
respectively, in continuously perfused, isolated canine gracilis
muscles and in muscles subjected to I/R alone, I/R+FDP, and I/R+ADO.
To determine whether FDP or ADO would attenuate leukocyte-endothelial
cell adhesive interactions induced by I/R, leukocyte adherence and
emigration were assessed in postischemic mouse cremaster muscles
using intravital microscopy in the presence and absence of FDP or ADO
during reperfusion. I/R was associated with a marked increase in
microvascular permeability (1-[sigma]=0.41+/-0.09) and muscle MPO
activity (8.8+/-1.7 U/g) relative to non-ischemic controls (0.11+/
-0.01 and 2.9+/-0.6 U/g, respectively). These increases were
attenuated by FDP (1-[sigma]=0.24+/-0.01; MPO=1.3+/-0.6 U/g) and ADO
(1-[sigma]=0.23+/-0.06; MPO=2.1+/-0.5 U/g). I/R also increased the
number of adherent leukocytes (AL) (from 4.2+/-1.0 to 47.7+/-1.7
leukocytes per 100 [mu]m length of venule) and emigrated leukocytes
(EL) (from 5.2+/-0.6 to 25.8+/-1.3 leukocytes per microscopic field)
relative to control. I/R-induced leukocyte adherence and emigration
were significantly attenuated by either FDP (AL=21.8+/-2.5 leukocytes
per 100 [mu]m length of venule, EL=12.5+/-1.0 leukocytes per
microscopic field) or ADO (AL=24.0+/-2.9 leukocytes per 100 [mu]m
length of venule, EL=13.8+/-3.1 leukocytes per microscopic field).
These results indicate that FDP and ADO attenuate postischemic
microvascular barrier dysfunction in skeletal muscle by a mechanism
that may be related to their ability to inhibit leukocyte adhesion
and emigration.
Received 21 December 1994; accepted in final form 15 May 1995.
APS Manuscript Number H1121-4.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 30 May 1995.