Thorac Cardiovasc Surg 2013; 61 - OP58
DOI: 10.1055/s-0032-1332297

Local epicardial Erythropoietin-plus-fibrin patch application more efficiently improves cardiac functions than intramyocardial and systemic delivery of Erythropoietin in a rat myocardial infarction model

C Klopsch 1, G Kleiner 1, R Gaebel 1, C Lux 1, M Ludwig 1, P Mela 2, S Jockenhoevel 2, A Kaminski 1, G Steinhoff 1
  • 1University of Rostock, Department of Cardiac Surgery, Rostock, Germany
  • 2RWTH Aachen University, Applied Medical Engineering, Helmholtz Institute for Biomedical Engineering, Aachen, Germany

Objectives: Rising evidence suggests Erythropoietin (EPO) protects the myocardium from ischemic injury and promotes beneficial remodelling when applied at higher dosage early after onset of ischemia. We investigated the therapeutic efficacy of EPO at a moderate dose level and compared local and systemic delivery routes in a rat myocardial infarction (MI) model.

Methods: Following MI, EPO (300 U/kg) was delivered immediately by intraperitoneal (EPO-S, n = 9) injection, intramyocardial (EPO-L, n = 9) injection or epicardially as an EPO-plus-fibrin patch (EPO-X, n = 6). Groups were compared to each other and MI control groups with saline injections (MIC, n = 8) or saline-plus-fibrin patch application (MIC-X, n = 6). Heart functions were examined under baseline and Dobutamine-induced stress conditions using conductance catheter method 6 weeks after MI. Moreover, blood samples were assessed 24 hours after MI. Histology analyses for early and late therapy-related effects are currently performed.

Results: Preliminary results illustrated superior cardiac functions in EPO-X compared with all groups at 6 weeks after MI. Pressure-volume loops in EPO-X demonstrated improved contractility with 38% higher peak rate of systolic pressure rise (dpdtmax), better elasticity with 47% greater peak rate of diastolic pressure decrease (dpdtmin) and 15% enhanced ejection fraction (EF) compared with MIC-X. Furthermore, dpdtmax was 33% and 22% higher and dpdtmin was 32% and 23% greater in EPO-X compared with EPO-S and EPO-L, respectively. EPO-L and EPO-S showed significant improvements in diastolic funtions and volume load compared with MIC, respectively. EF was 6% improved in EPO-L whereas it did not increase in EPO-S compared with MIC. At 24 hours after MI the hematopoietic effect of EPO was proved with increased reticulocyte counts in blood samples of EPO-S and EPO-L. The plasma level of cardiac troponin-t was lowest in EPO-L whereas plasma level of EPO was highest in EPO-X.

Conclusions: Local EPO delivery seemingly better than systemic application might restore cardiac performance after MI at a moderate dose level. Moreover, immediate but prolongated local EPO delivery via an epicardial EPO-plus-fibrin patch might further improve healing potentials and reduce the required EPO dosage for efficient MI treatment. Therapeutic efficacy therefore might be local-dose dependent. Underlying mechanisms are currently under intense investigation.