Attenuation of cardiac remodelling by endocardial injection of erythropoietin: ultrasonic strain-rate imaging in a model of hibernating myocardium.

Aims: The aim of this study was to investigate whether erythropoietin (EPO) has cardioprotective effects in a chronic myocardial ischaemia model regarding strain-rate imaging parameters during dobutamine stress echocardiography (DSE).

Methods And Results: An ameroid constrictor was placed around the circumflex artery in 13 pigs to induce hibernating myocardium by a chronic vessel occlusion. The pigs were randomized 14 days later: seven pigs receiving 10,000 U EPO and six pigs receiving placebo injected into the ischaemic region using a NOGAtrade mark-guided transendocardial catheter. At weeks 2 and 6, animals were examined by DSE, electromechanical mapping, and coronary angiography. During incremental dobutamine infusion, regional radial function was monitored by measuring peak systolic strain-rates (SRsys), systolic strains (epsilonsys), and post-systolic strains (epsilonps). At week 6, the animals were pathohistologically investigated. Echocardiography revealed 2.2+/-0.8 hypokinetic segments in the EPO-treated animals in comparison with 3.3+/-0.9 akinetic segments per animal in the controls. The mean ejection fraction was reduced in the control group (55+/-3 vs. 66+/-4%, P=0.057). Strain-rate imaging revealed ischaemic myocardium in EPO-treated animals and non-viable myocardium in the controls (P=0.0001). Histological analysis of the ischaemic region revealed a reduction of myocardial fibrosis (8+/-1 vs. 27+/-5%) in the EPO-treated group. The transmural extension of fibrosis and the echocardiographic deformation data correlated in the posterior walls (EPO group): epsilonsys at rest r=0.83; peak SRsys during dobutamine stimulation r=0.92, P=0.01.

Conclusion: Endocardial EPO injection may induce cardioprotective effects in chronic ischaemic myocardium and helps to obtain the myocardial contractile reserve, objectified by ultrasonic strain-rate imaging.