Biology Reference
In-Depth Information
Chapter 17
Myocardial Infarction: Cardioprotection by Erythropoietin
Mark I. Talan and Roberto Latini
Abstract
Extensive research during the last decade demonstrated that a single systemic administration of erythropoietin
(EPO) lead to significant attenuation of myocardial infarction (MI) induced in animals, mostly small
rodents, either by a myocardial ischemia followed by reperfusion or by a permanent ligation of a coronary
artery. Both methods are critically reviewed with the aim of helping the reader in appreciating key issues in
the translation of experimental results to the clinic. Results of several clinical trials in patients with acute
MI completed to date failed to demonstrate beneficial effects of EPO, and thus put into question the valid-
ity of results obtained in animal models. Comprehensive review of design and results of animal experiments
and clinical trials presented here allowed authors to postulate that therapeutic window for EPO during
developing MI is very narrow and was possibly missed in negative clinical trials. This point was illustrated
by the negative outcome of experiment in the rat model of MI in which timing of EPO administration was
similar to that in clinical trials. The design of future clinical trials should allow for a narrow therapeutic
window of EPO. Given current standards for onset-to-door and door-to-balloon time the optimal time for
EPO administration should be just prior to PCI.
Key words
Heart,
Cardiac,
Ischemia,
Ischemia-reperfusion,
Cardiomyocytes,
Clinical trials
1
Introduction
Chronic Heart Failure (CHF)—a debilitating condition that
reached epidemic proportion in the Western society and responsi-
ble for probably the largest portion of health care budget predomi-
nantly affecting the aging population. The major cause for severity
of developing CHF is the extent of myocardial damage during an
ischemic episode leading to a myocardial infarction (MI). Thus,
one strategic approach to reduce the severity of CHF is to limit the
extent of myocardial damage during an ischemic event. In spite of
a great progress achieved during the last 20 years to treat an acute
MI, mainly using timely revascularization of myocardium, the need
for additional therapies to limit myocardial damage remains on the
forefront of cardiovascular research.
The first experimental study demonstrating that exogenous
recombinant human erythropoietin rhEPO protects myocardium
Search WWH ::
Custom Search