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Fig. 1
Area of myocardium at risk (AAR) and size of myocardial infarction (MI) 24 h after permanent occlusion
of the left descending coronary artery or after 2 h of occlusion followed by 22 h of reperfusion. rhEPO is admin-
istered at the time of reperfusion (IR-EPO-0 h) or 4 h after beginning of reperfusion (IR-EPO-4 h) or 6 h after
permanent coronary occlusion (MI-EPO-6 h). Data presented as means ± SEM. AAR is presented as percent of
left ventricle (LV). MI is presented as percent of AAR or percent of LV. *
p
< 0.05 vs. all other group (Bonferroni
post hoc comparison)
exceed 12 h. In doses approaching acceptable therapeutic doses
the efficacy of EPO was lost even with small delay from the time of
coronary occlusion. These considerations drawn on the basis of
animal experiments were disregarded in the clinical trials design.
The issue whether this chasm stemmed from regulatory difficulties
in conducting clinical trial involving a patient in clinical emergency
that creates a pressure on clinicians to shorten the door-to-balloon
time and makes it difficult to obtain informed consent early enough,
or the problem is much deeper and have its roots in a growing
culture among clinical scientist not to accept data obtained from
animal research for anything more than proof of concept that can
serve only as a trigger to start independent clinical evaluation
deserves special discussion elsewhere.
Two, mostly used experimental MI models are permanent occlu-
sion of a coronary artery or temporary coronary occlusion followed
by a reperfusion (I/R model). Permanent occlusion is the most
“pure” experimental model, which allows studying and interven-
ing into the effects of ischemic damage of the myocardium per se.
Nevertheless, reperfusion following acute MI is the most effective
intervention to reduce the extent of injury and to improve clinical
outcomes, and contemporary treatment of MI always includes rep-
erfusion either by thrombolysis or by percutaneous coronary inter-
vention (PCI). In the light of this clinical mandate I/R experimental
model is more clinically relevant model with respect to translation
1.4 Experimental
Models of Myocardial
Infarction
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