Erythropoietin to Augment Myocardial Salvage Induced by Coronary Thrombolysis in Patients With ST Segment Elevation Acute Myocardial Infarction

Binbrek, Azan S.; Rao, Nayan S.; Khaja, Najib Al; Assaqqaf, Jamal; Sobel, Burton E.

doi:10.1016/j.amjcard.2009.05.050

Cited by 49 publications

(38 citation statements)

References 25 publications

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“…However, a recent study did not find any benefits of EPO in patients presenting with acute ischemic stroke and raised safety concern for its use, particularly in patients receiving thrombolytic therapy (32). Similarly, administration of high-dose intravenous EPO did not reduce infarct size in patients presenting with ST-segment elevation myocardial infarction who received thrombolytic therapy or percutaneous coronary intervention; the latter study found higher rates of adverse cardiovascular events in the EPO group (33,34).…”

Section: Discussionmentioning

confidence: 87%

Effect of High-Dose Erythropoietin on Graft Function after Kidney Transplantation

Sureshkumar

Hussain

et al. 2012

Clinical Journal of the American Society of Nephrology

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SummaryBackground and objectives Delayed graft function (DGF) is associated with adverse long-term outcomes after deceased-donor kidney (DDK) transplantation. Ischemia-reperfusion injury plays a crucial role in the development of DGF. On the basis of promising animal data, this study evaluated any potential benefits of erythropoietin-alfa (EPO-a) given intra-arterially at the time of reperfusion of renal allograft on the degree of allograft function, as well as tubular cell injury measured by urinary biomarkers in the early post-transplant period.Design, setting, participants, & measurements A prospective, randomized, double-blind, placebo-controlled clinical trial was conducted to evaluate the influence of EPO-a administered intraoperatively on the outcomes of DDK transplantations performed at the study center between March 2007 and July 2009.Results Seventy-two patients were randomly assigned to EPO-a (n=36) or placebo (n=36). The incidences of DGF, slow graft function, and immediate graft function did not significantly differ between the treatment and control groups (41.7% versus 47.2%, 25.0% versus 36.1%, and 33.3% versus 16.7%, respectively; P=0.24). The groups had similar levels of urinary biomarkers, including neutrophil gelatinase-associated lipocalin and IL-18 at multiple times points soon after transplantation; urinary output during the first 3 postoperative days; 1-month renal function; and BP readings, hemoglobin, and adverse effects during the first month.Conclusions This study did not show any clinically demonstrable beneficial effects of high-dose EPO-a given intra-arterially during the early reperfusion phase in DDK transplant recipients in terms of reducing the incidence of DGF or improving short-term allograft function.

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Section: Discussionmentioning

confidence: 87%

Effect of High-Dose Erythropoietin on Graft Function after Kidney Transplantation

Sureshkumar

Hussain

et al. 2012

Clinical Journal of the American Society of Nephrology

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“…2a). There was no statistical improvement in the LVEF with exclusion of any one of the trials performed by Ott et al [8], Binbrek et al [12], or Lipsic et al [13]. The WMD of LVESV and LVEDV at the end of the follow-up period between the ESAs and control groups were −2.26 (95% CI −6.15 to 1.63; p =0.26; Fig.…”

Section: Discussionmentioning

confidence: 83%

“…Among the remaining 16 RCTs, seven were ultimately excluded because they were duplicated reports or unfinished trials or they did not fulfill the inclusion criteria. The remaining nine RCTs [5][6][7][8][9][10][11][12][13] fulfilled our inclusion criteria and were included in this meta-analysis (Fig. 1).…”

Section: Selected Studies and Characteristicsmentioning

confidence: 99%

“…It has been suggested that drug treatments for acute myocardial infarction (AMI) that include erythropoiesis-stimulating agents (ESAs), such as recombinant human EPO and its analogue darbepoetin, may protect the affected myocardium, limit infarct size, and attenuate post-infarct remodeling when administered well after the onset of reperfusion [3,4]. Random control trials (RCTs) using either EPO or its analog darbepoetin [5][6][7][8][9][10][11][12][13] are currently underway to examine the clinical efficacy and safety of ESAs in patients with acute ST-segment elevation myocardial infarction (STEMI). Since the RCTs conducted to date have involved relatively limited sample sizes and have yielded heterogeneous results regarding to the effects of ESAs, we have performed a meta-analysis of results collected from clinical RCTs with the aim to explore the potential therapeutic effects and to assess the safety of EPO in the treatment of patients with acute STEMI.…”

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confidence: 99%

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Effect of erythropoiesis-stimulating agents in acute ST-segment elevation myocardial infarction: a systematic review

Gao

et al. 2011

Eur J Clin Pharmacol

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“…16 However, it is now well known that it has tissue-protective properties. [17][18][19][20] Furthermore, the authors have recently reported that EPO receptors (EpoR) are upregulated in human skeletal muscle obtained from patients with CLI, 21 suggesting the potential of EPO and its derivatives in treating CLI. The possible effect of EPO on preventing apoptosis in skeletal muscle and the pathways involved, however, are unknown and can be assessed using this model.…”

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confidence: 99%

Development of an in vitro model of myotube ischemia

Joshi

Patel

Baker

et al. 2011

Laboratory Investigation

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Critical limb ischemia causes severe damage to the skeletal muscle. This study develops a reproducible model of myotube ischemia by simulating, in vitro, the critical parameters that occur in skeletal muscle ischemia. Monolayers of C2C12 myoblasts were differentiated into mature myotubes and exposed to nutrition depletion, hypoxia and hypercapnia for variable time periods. A range of culture media and gas mixture combinations were used to obtain an optimum ischemic environment. Nuclear staining, cleaved caspase-3 and lactate dehydrogenase (LDH) release assay were used to assess apoptosis and myotube survival. HIF-1a concentration of cell lysates, pH of conditioned media as well as partial pressures of oxygen (PO 2 ) and carbon dioxide (PCO 2 ) in the media were used to confirm ischemic simulation. Culturing myotubes in depleted media, in a gas mixture containing 20% CO 2 þ 80% N 2 for 6-12 h increased the PCO 2 and decreased the pH and PO 2 of culture media. This attempts to mimic the in vivo ischemic state of skeletal muscle. These conditions were used to study the potential tissue-protective effects of erythropoietin (EPO) in C2C12 myotubes exposed to ischemia. EPO (60 ng/ml) suppressed LDH release, decreased cleaved caspase-3 and reduced the number of apoptotic nuclei, suggesting significantly decreased ischemia-induced apoptosis in myotubes (Po0.01) and a potential role in tissue protection. Additional therapeutic agents designed for tissue protection can also be evaluated using this model.

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Erythropoietin to Augment Myocardial Salvage Induced by Coronary Thrombolysis in Patients With ST Segment Elevation Acute Myocardial Infarction

Cited by 49 publications

References 25 publications

Effect of High-Dose Erythropoietin on Graft Function after Kidney Transplantation

Effect of High-Dose Erythropoietin on Graft Function after Kidney Transplantation

Effect of erythropoiesis-stimulating agents in acute ST-segment elevation myocardial infarction: a systematic review

Development of an in vitro model of myotube ischemia

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