Chronic Erythropoietin Treatment Limits Infarct-size in the Myocardium in Vitro |
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Authors: | Anthony?John?Bullard Email author" target="_blank">Derek?Miles?YellonEmail author |
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Institution: | (1) The Hatter Institute and Centre for Cardiology, University College London Hospital and Medical School, Grafton Way, London, UK, WC1E 6DB;(2) The Hatter Cardiovascular Institute and Centre for Cardiology, University College London Hospital and Medical School, Chenies Mews, London, WC1E 6DB, UK |
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Abstract: | Summary It has been well established that erythropoietin (EPO) can limit myocardial ischemia/reperfusion injury in a variety of acute
settings. However, despite EPO being used chronically to treat anemia the infarct limiting effects of long term treatment
(chronic) have never been fully investigated. In this study we examined the effects of a 3 week treatment of EPO (5,000 IU/Kg)
in male Sprague Dawley rats in limiting myocardial infarction after 35 min ischemia and 2 h reperfusion in an in vitro isolated heart perfusion model. Treating the animals ‘once a week’ failed to limit infarct size significantly compared to
a saline control (54.1% ± 3.5 v 52.3% ± 4.4), whereas a ‘3 times a week’ regime succeeded in significantly reducing infarct
size (36.2% ± 3.2 v 52.3% ± 4.4, p < 0.05). To demonstrate that the effect was not due to improved oxygen supply caused by a raised hematocrit level, we also
administered EPO 24 h prior to ischemia/reperfusion. This treatment again reduced infarct size compared to a saline control
(39.9% ± 4.4 v 58.4% ± 5.0, p < 0.05). To examine the mechanism of protection we used the PI3K inhibitor wortmannin and the nitric oxide synthase inhibitor
L-NAME to try to abrogate EPO mediated protection. Where wortmannin failed to block the effects of EPO (31.7% ± 6.0 v 36.2% ± 3.2),
L-NAME did abrogate protection (51.6% ± 5.6 v 36.2% ± 3.2, p < 0.05). We demonstrate that chronic EPO treatment limits infarct size and that it does so in a nitric oxide dependent manner. |
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Keywords: | ischemia reperfusion infarction kinases |
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