Lack of acute cardioprotective effect from preischaemic erythropoietin administration in a porcine coronary occlusion model

Clin Physiol Funct Imaging. 2005 Sep;25(5):305-10. doi: 10.1111/j.1475-097X.2005.00626.x.

Abstract

Background: Recombinant human erythropoietin (rhEPO) has been proposed to possess important tissue protective, apart from haematopoietic, effects. Cardioprotective effects have thus been reported in rodents exposed to myocardial ischaemia. Pathways common to the mediation of ischaemic preconditioning may be involved. Before clinical testing such possible cardioprotective effects needs assessment in an experimental large animal model with closer similarity to human ischaemic pathophysiology.

Methods: A control group and two rhEPO groups were studied. EPO1 pigs were given EPO corresponding to the early window and EPO2 pigs to the early and late window of ischaemic preconditioning in a closed chest, catheter-based, porcine coronary occlusion model (45 min of occlusion of the left anterior descending artery). Infarct size as a proportion of the ischaemic area (IS/AAR) was measured in vivo by myocardial perfusion imaging (MPI) and postmortem by a histochemical procedure (at 150 min of reperfusion).

Results: IS/AAR did not differ significantly between control (C), EPO1 and EPO2 groups, neither measured by MPI (mean+/-SD for C: 0.87+/-0.13; EPO1: 0.92+/-0.08; EPO2: 0.87+/-0.11), nor histochemically (mean+/-SD for C: 0.64+/-0.20; EPO1: 0.75+/-0.17; EPO2: 0.80+/-0.07). In the EPO2 group mean arterial pulmonary pressure and dP/dtmax were increased compared with control group.

Conclusion: Despite promising results from studies in rodents, rhEPO did not reduce infarct size measured after 2.5 h of reperfusion in our porcine model.

MeSH terms

  • Animals
  • Blood Pressure / drug effects
  • Cardiac Output / drug effects
  • Cardiotonic Agents / pharmacology*
  • Coronary Stenosis / diagnostic imaging
  • Coronary Stenosis / physiopathology*
  • Disease Models, Animal
  • Erythropoietin / pharmacology*
  • Myocardial Infarction / diagnostic imaging
  • Myocardial Infarction / physiopathology
  • Myocardial Ischemia / physiopathology
  • Recombinant Proteins
  • Swine
  • Tomography, Emission-Computed, Single-Photon

Substances

  • Cardiotonic Agents
  • Recombinant Proteins
  • Erythropoietin