Single high-dose erythropoietin administration immediately after reperfusion in patients with ST-segment elevation myocardial infarction: results of the Erythropoietin in Myocardial Infarction Trial

Prunier, Fabrice; Bière, Loïc; Gilard, Martine; Boschat, J; Mouquet, Frédéric; Bauchart, Jean-Jacques; Charbonnier, B; Genée, Olivier; Guérin, Patrice; Warin-Fresse, K.; Durand, Éric; Lafont, Antoine; Christiaens, Luc; Abi-Khalil, Wissam; Delépine, Stéphane; Benard, Thomas; Furber, Alain

doi:10.1016/j.ahj.2011.11.005

Cited by 45 publications

(21 citation statements)

References 28 publications

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“…The dose used has been safely tested in humans. 9,13,29 Our results suggest that intravenous administration of a single 1000-IU/kg dose of rhEPO just prior to a transitory occlusion of a cerebral artery may decrease secondary brain insult, resulting in a better neurological outcome.…”

Section: Discussionmentioning

confidence: 82%

Neuroprotective effects of erythropoietin pretreatment in a rodent model of transient middle cerebral artery occlusion

Ratilal

Arroja

Rocha

et al. 2014

JNS

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Object There is an unmet clinical need to develop neuroprotective agents for neurosurgical and endovascular procedures that require transient cerebral artery occlusion. The aim in this study was to explore the effects of a single dose of recombinant human erythropoietin (rhEPO) before middle cerebral artery (MCA) occlusion in a focal cerebral ischemia/reperfusion model. Methods Twenty-eight adult male Wistar rats were subjected to right MCA occlusion via the intraluminal thread technique for 60 minutes under continuous cortical perfusion monitoring by laser Doppler flowmetry. Rats were divided into 2 groups: control and treatment. In the treated group, rhEPO (1000 IU/kg intravenously) was administered 10 minutes before the onset of the MCA ischemia. At 24-hour reperfusion, animals were examined for neurological deficits, blood samples were collected, and animals were killed. The following parameters were evaluated: brain infarct volume, ipsilateral hemispheric edema, neuron-specific enolase plasma levels, parenchyma histological features (H & E staining), Fluoro-Jade–positive neurons, p-Akt and total Akt expression by Western blot analysis, and p-Akt–positive nuclei by immunohistochemical investigation. Results Infarct volume and Fluoro-Jade staining of degenerating neurons in the infarct area did not vary between groups. The severity of neurological deficit (p < 0.001), amount of brain edema (78% reduction in treatment group, p < 0.001), and neuron-specific enolase plasma levels (p < 0.001) were reduced in the treatment group. Perivascular edema was histologically less marked in the treatment group. No variations in the expression or localization of p-Akt were seen. Conclusions Administration of rhEPO before the onset of 60-minute transient MCA ischemia protected the brain from this insult. It is unlikely that rhEPO pretreatment leads to direct neuronal antiapoptotic effects, as supported by the lack of Akt activation, and its benefits are most probably related to an indirect effect on brain edema as a consequence of blood-brain barrier preservation. Although research on EPO derivatives is increasing, rhEPO acts through distinct neuroprotective pathways and its clinical safety profile is well known. Clinically available rhEPO is a potential therapy for prevention of neuronal injury induced by transitory artery occlusion during neurovascular procedures.

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Section: Discussionmentioning

confidence: 82%

Neuroprotective effects of erythropoietin pretreatment in a rodent model of transient middle cerebral artery occlusion

Ratilal

Arroja

Rocha

et al. 2014

JNS

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“…However, larger studies did not demonstrate a reduction in infarct size with EPO treatment [218,219,220,221]. The Reduction of Infarct Expansion and Ventricular Remodeling With Erythropoietin After Large Myocardial Infarction (REVEAL) trial included patients with ST-segment elevation myocardial infarction (STEMI) with successful percutaneous coronary intervention or rescue reperfusion strategy and utilized EPO treatment within 4 h of reperfusion, demonstrated no reduction in infarct size and was associated with higher rates of adverse cardiovascular events [218].…”

Section: Epo Therapy and Associated Adverse Eventsmentioning

confidence: 99%

Erythropoietin Action in Stress Response, Tissue Maintenance and Metabolism

Zhang

Wang²,

Dey

et al. 2014

IJMS

104

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Erythropoietin (EPO) regulation of red blood cell production and its induction at reduced oxygen tension provides for the important erythropoietic response to ischemic stress. The cloning and production of recombinant human EPO has led to its clinical use in patients with anemia for two and half decades and has facilitated studies of EPO action. Reports of animal and cell models of ischemic stress in vitro and injury suggest potential EPO benefit beyond red blood cell production including vascular endothelial response to increase nitric oxide production, which facilitates oxygen delivery to brain, heart and other non-hematopoietic tissues. This review discusses these and other reports of EPO action beyond red blood cell production, including EPO response affecting metabolism and obesity in animal models. Observations of EPO activity in cell and animal model systems, including mice with tissue specific deletion of EPO receptor (EpoR), suggest the potential for EPO response in metabolism and disease.

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“…71 Additionally, a different regime of 1000 IU/kg of EPO given intravenously immediately following reperfusion in a randomized trial by Prunier et al showed a reduced incidence of MVO in the EPO group along with a short-term improvement in LV volume and function. 72 Similar intravenous regimes in 2 other trials showed improvement in LV function in favor of EPO. 73,74 Thus, the infarct-reducing capabilities of EPO may be demonstrated, if the dosage, timing, and route of administration are optimized.…”

Section: Erythropoeitinmentioning

confidence: 91%

Pharmacologic Therapy That Simulates Conditioning for Cardiac Ischemic/Reperfusion Injury

Sivaraman

Yellon

2013

J Cardiovasc Pharmacol Ther

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Cardiovascular disease remains a leading cause of deaths due to noncommunicable diseases, of which ischemic heart disease forms a large percentage. The main therapeutic strategy to treat ischemic heart disease is reperfusion that could either be medical or surgical. However, reperfusion following ischemia is known to increase the infarct size further. Newer strategies such as ischemic preconditioning (IPC), ischemic postconditioning, and remote IPC have been shown to condition the myocardium to ischemia-reperfusion injury and thus reduce the final infarct size. Research over the past 3 decades has deepened our understanding of cellular and subcellular pathways that mediate ischemia-reperfusion injury. This in turn has resulted in the development of several pharmacological agents that act as conditioning agents, which reduce the final myocardial infarct size following ischemia-reperfusion. This review discusses many of these agents, their mechanisms of action, and the animal and clinical evidence behind them.

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Single high-dose erythropoietin administration immediately after reperfusion in patients with ST-segment elevation myocardial infarction: results of the Erythropoietin in Myocardial Infarction Trial

Cited by 45 publications

References 28 publications

Neuroprotective effects of erythropoietin pretreatment in a rodent model of transient middle cerebral artery occlusion

Neuroprotective effects of erythropoietin pretreatment in a rodent model of transient middle cerebral artery occlusion

Erythropoietin Action in Stress Response, Tissue Maintenance and Metabolism

Pharmacologic Therapy That Simulates Conditioning for Cardiac Ischemic/Reperfusion Injury

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