Biology Reference
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In another study employing a permanent ligation model in
rabbits (
13
) a single dose of 5,000 IU/kg of epoetin-alfa was
injected immediately after ligation (the route of injection was not
reported) and animals were sacrificed 4 days after surgery. AAR
was not different between groups. While the number of TUNEL-
positive cells in the AAR at 6 h after ligation was 50% less in the
EPO-treated animals, the MI size at day 4 had only a tendency to
be smaller (
p
< 0.1).
In 2005, in experiments on rats van der Meer et al. (
14
) used
8,000 IU/kg of Darbepoetin alfa, prolong action epoetin, in three
different treatment strategies: (1) a single dose of EPO immedi-
ately after coronary ligation, (2) repeated doses of EPO every 3
weeks starting the first dose immediately after coronary ligation,
and (3) repeated doses of EPO every 3 weeks starting the first dose
3 weeks after coronary ligation. Experiment lasted 9 weeks. At the
end of 9 weeks MI size was significantly smaller in groups 1 and 2,
i.e., in groups in which treatment was started immediately after
coronary ligation. There were no effects on the MI size in group 3
(treatment started 3 weeks after coronary ligation) and there were
no differences in the magnitude of effect on the MI size between
groups 1 and 2. Capillary density was significantly increased in all
three treatment groups and there were no differences in the mag-
nitude of effect.
Study reported by Hale et al. (
15
) is the only one among
studies employing the permanent coronary occlusion model with
clearly negative results. 24 h prior coronary ligation rats had
been injected subcutaneously with 5,000 IU/kg of Epoetin alfa.
The dose had been repeated at the day of ligation (20-25 min
before occlusion), and five more times daily. Six weeks after sur-
gery there were no significant effects of treatment either with
respect to MI size or with respect to LV volume and function. It
was noted, however, that at each given MI size the EF was higher
in the EPO treated animals. Notably, after 7 days the hematocrit
in the EPO treated rats was elevated to 67%, compared to 45% in
untreated animals.
Hirata et al. (
16
) studied the effect of EPO in the dog experi-
mental model of MI. rhEPO (type of EPO is not reported) had
been injected as a single bolus intravenously in three different
treatment groups either immediately after permanent coronary
occlusion (0 group), or 6 h after occlusion (6 h group), or 1 week
after occlusion (1 week group). Six hours after occlusion (0 group)
MI was statistically smaller in the EPO treated group vs. control.
One week after occlusion the number of progenitor cells was
increased in the both EPO treated groups (0 group and 6 h
group). Measured 4 weeks after occlusion, the MI was significantly
smaller only in the 0 group; EF and capillary density were increased
in the 0 group and 6 h group, but not in 1 week group of EPO
treated dogs.
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