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1 Lawson Health Research Institute, Departments of 2 Surgery and 3 Medical Biophysics, University of Western Ontario, London, Ontario N6A 4G5, Canada; and 4 Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, Vienna A-1090, Austria
The role of leukocytes and nonleukocyte-derived reactive oxygen
metabolites (ROMs) in reperfusion-induced skeletal muscle injury was
determined. Male rats received 2 h no-flow hindlimb ischemia-reperfusion (I/R, n = 6) or were
rendered neutropenic via antineutrophil serum (ANS) before I/R
(I/R + ANS, n = 5). Oxygen radicals in the absence of
neutrophils were tested by administration of dimethylthiourea (DMTU)
(I/R + ANS + DMTU, n = 5). Perfused capillaries
(CDper) and rolling (Lr), adherent
(La), and extravasated leukocytes (Le) in the
extensor digitorum longus muscle were measured every 15 min during 90 min of reperfusion using intravital microscopy. The vital dyes
bisbenzimide (BB) and ethidium bromide (EB) provided direct measures of
tissue injury (EB/BB). CDper decreased immediately on
reperfusion in the I/R and I/R + ANS groups. CDper in
the I/R + ANS + DMTU group remained at baseline throughout
reperfusion. La increased in the I/R group; however, EB/BB
was the same between I/R and I/R + ANS groups. Injury in the
I/R + ANS + DMTU group did not differ from other groups
60
min, after which EB/BB became significantly lower. Le did
not differ between groups and was highly correlated to tissue injury.
The results suggest that Le lead to parenchymal injury, and
ROMs lead to perfusion deficits during the early reperfusion period
after ischemia.
reactive oxygen; dimethylthiourea; neutropenia
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