Biology Reference
In-Depth Information
Recently (2011) the effect of EPO has been tested in the
mini-pig model of MI (
17
). 7,500 IU/kg of EPO (type is not
reported) was injected 30 min following coronary occlusion. The
dose had been repeated once, 24 h later. Fourteen days after sur-
gery MI size was smaller and EF was higher in EPO-treated in
comparison with placebo-treated animals. In the hearts of the EPO
group there were less fibrosis and higher capillary density. Apoptosis
in the peri-infarct area was reduced.
Therapeutic window and effective dose of EPO in the rat
model of permanent coronary occlusion had been systematically
studied by Moon et al. (
9
). In the first experiment five different
doses (3,000, 1,000, 500, 150, and 50 IU/kg) were injected intra-
peritoneally immediately after coronary ligation. Apoptosis in the
AAR 24 h after treatment measured as a number of TUNEL posi-
tive nuclei was significantly reduced in all treatment groups except
one, treated with the lowest, 50 IU/kg, dose. All doses, but
50 IU/kg were also found effective 4 weeks after coronary ligation
with respect to reduction of MI size, LV remodeling and preserva-
tion of EF. In the second experiment 3,000 IU/kg had been
injected with different delays after coronary ligation (0 min, 4, 8,
12, and 24 h). Four weeks after surgery MI was significantly smaller
and EF significantly less reduced in all delayed treatment groups,
except when treatment had been delayed by 24 h. In the final
experiment the smallest effective dose (150 IU/kg) was injected
with the same delays as in the second experiment. Four weeks later
it was found that this dose was effective only if injected immedi-
ately. Any delay longer than 4 h did not affect the MI size or LV
remodeling. In the group where 150 IU/kg treatment was delayed
by 4 h, EF was higher and MI was smaller than in untreated group,
but with respect to MI size the difference did not reach statistical
significance (
p
< 0.07).
Finally, using the rat model of permanent coronary occlusion
(
10
), the effect of a single dose of 3,000 IU/kg injected immedi-
ately after coronary ligation had been compared with the effect of
treatment when immediate dose of 3,000 IU/kg was supple-
mented with seven more daily injections at the same dose.
Comparing with untreated animals 4 weeks after surgery LV
remodeling and the reduction of EF were similarly attenuated in
single dose and repeated dose groups. However, the reduction of
MI size was statistically significant only in the group treated with a
single dose.
Therefore, all published studies but one demonstrated that in
the experimental model of MI induced by a permanent occlusion
of a coronary artery in rats, dogs, and mini-pigs high dose of
rhEPO (³3,000 IU/kg) applied after coronary ligation effectively
protects myocardium from ischemic damage by reducing apoptosis
in the area at risk resulting in smaller MI size and attenuated LV
remodeling. The effect is clearly dose-depended and has a narrow
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