Following A Heart Attack 1 Dose Of EPO May Halt Cell Suicide

Main Category: Cardiovascular / Cardiology
Also Included In: Biology / Biochemistry;  Endocrinology;  Radiology / Nuclear Medicine
Article Date: 09 Oct 2008 - 5:00 PDT

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Two things happen following a heart attack - necrosis (normal cell death) and apoptosis (programmed cell death) - and both are bad. Now researchers in Japan have found that a single intravenous dose of the hormone erythropoietin (EPO) immediately after myocardial infarction (heart attack) can drastically reduce or eliminate apoptosis and thereby limit the amount of damage to the heart, according to an article in the October issue of The Journal of Nuclear Medicine.

"The study's concept is very novel. We wanted to see if the area of cell death following acute coronary occlusion could be reduced by a single dose of EPO," said H William. Strauss, M.D., attending physician in the Nuclear Medicine Service at Memorial Sloan Kettering Cancer Center, professor of radiology at Weill Cornell School of Medicine and a co-author of the manuscript. "Cells deprived of blood quickly begin to die. By administering 99mTc-annexin V, a radiotracer with a high affinity for apoptotic cells, we were able to view the effects of EPO on heart cells immediately following the restriction of blood flow that occurs during MI."

In the study, 18 Wistar rats were randomized into two groups. In both groups, arteries were blocked to induce a heart attack; 20 minutes later, they were unblocked. Immediately afterward, one group (treatment) received an injection of EPO and the other group of saline (non-treatment). Both groups were then injected with 99mTc-annexin V, and their hearts were examined using autoradiography to evaluate the distribution of the radiotracer. In the treatment group, EPO therapy caused a 2.7-fold reduction of tracer accumulation, indicating a reduction in apoptosis and, therefore, less damage to heart tissue. The reduction in damage to the heart was also demonstrated by measurement of regional cardiac function, which was significantly better in the EPO-treated group. These findings suggest that EPO may be useful to prevent long-term heart damage and dysfunction after a heart attack.

"Although other drugs to inhibit apoptosis have been studied, none appears nearly as effective as a single dose of EPO," Strauss said.

EPO is a naturally occurring hormone that promotes the formation of red blood cells in the bone marrow. It was first produced artificially to aid in the treatment of anemia. More recently, scientists discovered its cardioprotective capability in minimizing apoptosis.

Apoptosis is sometimes referred to as "cell suicide," because the biochemically programmed mechanism triggers damaged cells to self-destruct, albeit in an orderly way. Researchers have found that cells can die by several pathways, only one of which is apoptosis. Because cell death is central to normal physiology and numerous disease states, research into apoptosis is ongoing in a variety of medical areas, including oncology and cardiology.

"In cardiovascular medicine, imaging of apoptosis could be highly useful in managing myocardial infarction, atherosclerotic plaques [hardening of the arteries] and cardiac allograft rejection [heart transplant rejection]. Because molecular probes such as 99mTc-annexin V are capable of imaging apoptosis in living patients, they are vital to this research," said Robert W. Atcher, Ph.D., president of SNM, an international scientific and medical association dedicated to advancing molecular imaging and therapy.

"More translational research is needed to evaluate cell death pathways and their significance for imaging in the diagnosis or monitoring of disease. SNM is currently working with molecular imaging practitioners, government agencies and pharmaceutical manufacturers to streamline the process to progress promising molecular imaging agents from the laboratory into the clinical setting, " Atcher added.

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Article adapted by Medical News Today from original press release.
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Coauthors of "Cardioprotective Effects of Erythropoietin in Rats Subjected to Ischemia-Reperfusion Injury: Assessment of Infarct Size with 99mTc-Annexin V" include Katsuichi Ohtsuki and Tomoki Doue, Department of Cardiology and Nephrology, Kyoto Prefectural University of Medicine, Kyoto, Department of Medicine, Kyoto, and Meiji University of Integrative Medicine, Nantan; Akihiro Azuma and Hiroaki Matsubara, Department of Cardiology and Nephrology, Kyoto Prefectural University of Medicine, Kyoto; Kazuma Ogawa, Division of Tracer Kinetics, Advanced Science Research Center, Kanazawa University, Kanazawa; Masashi Ueda, Radioisotopes Research Laboratory, Kyoto University Hospital Faculty of Medicine, Kyoto University, Kyoto; Hideo Saji, Department of Patho-Functional Bioanalysis, Graduate School of Pharamceutical Sciences, Kyoto University, Kyoto, all of Japan; and H. William Strauss, Division of Nuclear Medicine, Department of Radiology, Memorial Sloan-Kettering Hospital, New York, N.Y.

About SNM

SNM is an international scientific and medical organization dedicated to raising public awareness about what molecular imaging is and how it can help provide patients with the best health care possible. SNM members specialize in molecular imaging, a vital element of today's medical practice that adds an additional dimension to diagnosis, changing the way common and devastating diseases are understood and treated.

SNM's more than 17,000 members set the standard for molecular imaging and nuclear medicine practice by creating guidelines, sharing information through journals and meetings and leading advocacy on key issues that affect molecular imaging and therapy research and practice. For more information, visit http://www.snm.org/.

Source: Amy Shaw
Society of Nuclear Medicine