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from ANILAB (Campinas, SP, Brazil). Experiments
were performed according to protocols approved by
the Ethical Committee of the State University of Rio
de Janeiro (H36/94). Animals received appropriate labo-
ratory diet (Nuvital, Nuvilab, Paulinia, PR, Brazil). All
drugs tested were administered by gavage, at a dose of
3 mg/kg body weight, 30 min before the induction of
anesthesia by an intraperitoneal injection of sodium
pentobarbital and maintained with a-chloralose admin-
istered through the femoral vein. The femoral artery was
also cannulated for pressure measurements. Throughout
surgery and the subsequent experiment, the temperature
of the animals was kept at 37.5 ꢁC with a heating pad
controlled by a rectal thermistor. A tracheal tube was in-
serted to facilitate spontaneous breathing. The cheek
pouch was everted gently and pinned with four to five
needles into a circular well filled with silicone rubber
to provide a flat bottom layer, thus avoiding stretching
of the tissue, but preventing shrinkage. In this position,
the pouch was submerged in a superfusion solution that
continuously flushed the pool of the microscope stage.
In order to produce a single-layer preparation, an inci-
sion was made in the upper layer so that a triangular
flap could be displaced to one side.
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Thirty minutes after the completion of the preparative
procedure, FITC-dextran 150 (Bioflor HB, Uppsala,
Sweden) was given as an intravenous injection of a 5%
solution in 0.9% saline. Local ischemia of the cheek
pouch was produced by means of a cuff, made of thin
latex tubing, which was mounted around the neck of
the everted pouch where it leaves the mouth of the ham-
ster. An intracuff pressure of 200–220 mmHg resulted in
a complete arrest of microvascular blood flow within
few seconds. Throughout the 30-min occlusion period,
minor adjustments of blood movements could be seen
in the larger vessels.
The fluorescent spots formed at leakage sites could be
traced when they reached a certain minimal size and
fluorescent intensity. Each was classified as a leakage
site when its diameter was >100 lm, expressed by cm2.
The maximum number of leaks occurred 10 min after
the onset of reperfusion and it is reported in the result
section.
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