Endogenous erythropoietin and a single bolus of 40,000 IU of epoetin alpha do not protect the heart from ischaemia-reperfusion injury during extracorporeal circulation for cardiac surgery

Abstract

Erythropoietin (EPO) exerts a tissue-protective activity in several non-haematopoietic tissues such as heart, brain, spinal cord and muscle. We evaluated the relationship between pre-operative endogenous EPO blood levels and myocardial damage in patients undergoing cardiopulmonary bypass (CPB). Furthermore, we investigated whether pre-operative administration of a single bolus of 40,000 IU epoetin alpha (EPOα) would reduce troponin I or creatine kinase isoenzyme (CK-MB) after on-pump coronary artery bypass graft (CABG) surgery. Sixty-seven patients (45 CABG, 22 valvular surgery) were enrolled. EPO was measured in the pre-surgical period and correlated to post-surgical troponin I and CK-MB peaks. Subsequently, forty patients scheduled for CABG were randomized into two groups, receiving, respectively, a) standard medical and surgical treatment (20 patients) and b) the same treatment plus 40,000 IU of EPOα in a single bolus injection in the immediate pre-surgical period (20 patients). In our population, we did not find any correlation between pre-surgical EPO and post-surgical troponin I or CK-MB peaks (p Pearson > 0.05). Furthermore, patients treated with EPOα did not show differences compared to the control group in either troponin I (1.7±1.8 vs 2.6±3.4, p>0.05) or CK-MB (19.6 ±13.2 vs 17.1±12.6, p>0.05) peaks measured in the post-surgical period.

Keywords

epoetin alpha erythropoietin ischaemia myocardial reperfusion injury

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References

1 Fisher JW . Erythropoietin: physiology and pharmacology update. Exp Biol Med (Maywood) 2003; 228(1): 1–14.

2 Maiese K Li F Chong ZZ . New avenues of exploration for erythropoietin. Jama 2005; 293(1): 90–95.

3 Mocini D Leone T Tubaro M . Structure, production and function of erythropoietin: implications for therapeutical use in cardiovascular disease. Curr Med Chem 2007; 14(21): 2278–2287.

4 Siren AL Fratelli M Brines M . Erythropoietin prevents neuronal apoptosis after cerebral ischaemia and metabolic stress. Proc Natl Acad Sci U S A 2001; 98(7): 4044–4049.

5 Celik M Gokmen N Erbayraktar S . Erythropoietin prevents motor neuron apoptosis and neurologic disability in experimental spinal cord ischemic injury. Proc Natl Acad Sci U S A 2002; 99(4): 2258–2263.

6 Calvillo L Latini R Kajstura J . Recombinant human erythropoietin protects the myocardium from ischaemia-reperfusion injury and promotes beneficial remodeling. Proc Natl Acad Sci U S A 2003; 100(8): 4802–4806.

7 Moon C Krawczyk M Ahn D . Erythropoietin reduces myocardial infarction and left ventricular functional decline after coronary artery ligation in rats. Proc Natl Acad Sci U S A 2003; 100(20): 11612–11617.

8 Parsa CJ Matsumoto A Kim J . A novel protective effect of erythropoietin in the infarcted heart. J Clin Invest 2003; 112(7): 999–1007.

9 Rafiee P Shi Y Su J . Erythropoietin protects the infant heart against ischaemia-reperfusion injury by triggering multiple signaling pathways. Basic Res Cardiol 2005; 100(3): 187–197.

10.

10 Ogilvie M Yu X Nicolas-Metral V . Erythropoietin stimulates proliferation and interferes with differentiation of myoblasts. J Biol Chem 2000; 275(50): 39754–39761.

11.

11 Hirata A Minamino T Asanuma H . Erythropoietin enhances neovascularization of ischemic myocardium and improves left ventricular dysfunction after myocardial infarction in dogs. J Am Coll Cardiol 2006; 48(1): 176–184.

12.

12 Hausenloy DJ Yellon DM . New directions for protecting the heart against ischaemia-reperfusion injury: targeting the Reperfusion Injury Salvage Kinase (RISK)-pathway. Cardiovasc Re 2004; 61(3): 448–460.

13.

13 Namiuchi S Kagaya Y Ohta J . High serum erythropoietin level is associated with smaller infarct size in patients with acute myocardial infarction who undergo successful primary percutaneous coronary intervention. J Am Coll Cardiol 2005; 45(9): 1406–1412.

14.

14 Wright GL Hanlon P Amin K . Erythropoietin receptor expression in adult rat cardiomyocytes is associated with an acute cardioprotective effect for recombinant erythropoietin during ischaemia-reperfusion injury. Faseb J 2004; 18(9): 1031–1033.

15.

15 Mengozzi M Latini R Salio M . Increased erythropoietin production after myocardial infarction in mice. Heart 2006; 92(6): 838–839.

16.

16 Negoro S Kunisada K Tone E . Activation of JAK/STAT pathway transduces cytoprotective signal in rat acute myocardial infarction. Cardiovasc Res 2000; 47(4): 797–805.

17.

17 Tramontano AF Muniyappa R Black AD . Erythropoietin protects cardiac myocytes from hypoxia-induced apoptosis through an Akt-dependent pathway. Biochem Biophys Res Commun 2003; 308(4): 990–994.

18.

18 Lipsic E van der Meer P Voors AA . A single bolus of a long-acting erythropoietin analogue darbepoetin alfa in patients with acute myocardial infarction: a randomized feasibility and safety study. Cardiovasc Drugs Ther 2006; 20(2): 135–141.