European Heart Journal Advance Access originally published online on January 22, 2007
European Heart Journal 2007 28(4):499-509; doi:10.1093/eurheartj/ehl439
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Attenuation of cardiac remodelling by endocardial injection of erythropoietin: ultrasonic strain-rate imaging in a model of hibernating myocardium
1 Department of Cardiology, Asklepios Klinik, St. Georg II. Med. Abteilung (Kardiologie), Lohmühlenstraße 5, 20099 Hamburg, Germany
2 Department of Cardiac Surgery, St. Georg Hospital, Hamburg, Germany
3 Institute of Experimental and Clinical Pharmacology, University Medical Center Hamburg-Eppendorf, Germany
Received 29 June 2006; revised 8 November 2006; accepted 23 November 2006; online publish-ahead-of-print 22 January 2007.
* Corresponding author. Tel: +49 40 2890 2305; fax: +49 40 2890 4444. E-mail address: dr_c_schneider{at}hotmail.com
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 NOGATM-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 (
sys), and post-systolic strains (ps). 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): sys 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.
Key Words: Dobutamine stress echocardiography • Strain-rate imaging • Myocardial viability • Erythropoietin
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