Erythropoietin improves left ventricular function and coronary flow in an experimental model of ischemia-reperfusion injury.
BACKGROUND
Recent studies show that erythropoietin (EPO) plays a protective role in brain ischemia. In this condition, administration of EPO protects neurons from ischemic damage. Recently, it has been shown that in patients with chronic heart failure (CHF), EPO treatment improved cardiac function. In the present study we assessed the role of EPO and EPO-receptor (EPO-R) in the heart.


RESULTS
We studied the presence and functionality of the EPO-R in isolated rat hearts in the Langendorff set-up. Hearts were perfused for 20 min with 10 U/ml EPO or vehicle. Immunohistochemistry revealed the presence of the EPO-R on endothelial cells, fibroblasts and to a lesser extent cardiomyocytes. Furthermore, perfusion with EPO resulted in a 50% increase in the phosphorylated MAP kinases p42/p44. To evaluate the protective role of EPO in cardiac ischemia, we performed low-flow (0.6 ml/min) ischemia/reperfusion experiments in isolated rat hearts. Administration of EPO (10 U/ml) reduced the cellular damage by 56% (P<0.05) during reperfusion, diminished apoptosis by 15% (P<0.05) and resulted in a significantly improved recovery of left ventricular pressure (P=0.02) and coronary flow (P=0.01).


CONCLUSIONS
The present data suggest that a functional EPO-R is present in rat adult cardiac tissue and that exogenous EPO administration improves cardiac function after ischemia/reperfusion injury.
van der Meer
Peter
P
Department of Cardiology, University Hospital Groningen, Groningen, The Netherlands.
Lipsic
Erik
E
Henning
Robert H
RH
de Boer
Rudolf A
RA
Suurmeijer
Albert J H
AJ
van Veldhuisen
Dirk J
DJ
van Gilst
Wiek H
WH
D000818:Animals; D003326:Coronary Circulation; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D004921:Erythropoietin / Q000008:administration & dosage* / Q000378:metabolism*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D020928:Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism; D008955:Models, Cardiovascular; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017467:Receptors, Erythropoietin / Q000378:metabolism; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology*; D015398:Signal Transduction / Q000187:drug effects; D016277:Ventricular Function, Left
D017467:Receptors, Erythropoietin; D004921:Erythropoietin; D020928:Mitogen-Activated Protein Kinases