European Heart Journal Advance Access originally published online on June 10, 2008
European Heart Journal 2008 29(15):1911-1921; doi:10.1093/eurheartj/ehn218
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Role of balloon occlusion for mononuclear bone marrow cell deposition after intracoronary injection in pigs with reperfused myocardial infarction
1 Department of Cardiothoracic Surgery, University of Essen, Essen, Germany
2 Laboratory of Muscle Research and Molecular Cardiology, Department of Internal Medicine III, University of Cologne, Kerpener Str 62, 50937 Köln, Germany
3 Department of Nuclear Medicine, University of Cologne, Köln, Germany
4 Institute of Pathology, University of Cologne, Köln, Germany
5 Institute of Medical Statistics, Informatics and Epidemiology, University of Cologne, Köln, Germany
6 Institute for Experimental Medicine, University of Cologne, Köln, Germany
7 German Sports University, Cologne, Köln, Germany
8 Department of Cardiothoracic Surgery, University of Mainz, Mainz, Germany
9 Department of Internal Medicine II, Klinikum Weiden, Weiden, Germany
Received 19 November 2007; revised 15 April 2008; accepted 6 May 2008; online publish-ahead-of-print 10 June 2008.
*Corresponding author. Tel: +49 221 478 32356, Fax: +49 221 478 32355, Email: muller.ehmsen{at}uni-koeln.de
Aims: In clinical studies on cell therapy for acute myocardial infarction (MI), cells are usually applied by intracoronary infusion with balloon (IC/B). To test the utility of balloon occlusion, mononuclear bone marrow cell (MNC) retention after intracoronary infusion without balloon (IC/noB) was compared with IC/B and intramyocardial (IM) injection.
Methods and results: Four hours after LAD ligation in male pigs, reperfusion was allowed (confirmed by coronary angiography). Five days later, 1 x 108 autologous 111Indium-labelled MNC were injected IC/noB (n = 4), IC/B (n = 4), or IM (n = 4). At 1 h the fraction of injected MNC that was detected in the heart was 4.1 ± 1.1% after IC/noB injection, 6.1 ± 2.5% after IC/B injection (P = 0.19), and 20.7 ± 2.3% after IM injection (P < 0.001 vs. IC/noB and IC/B). At 24 h it was 3.0 ± 0.6% (IC/noB), 3.3 ± 0.5% (IC/B, P = 0.43), and 15.0 ± 3.1% (IM, P < 0.001 vs. IC/noB and IC/B). Dynamic scintigrammes during each of four consecutive IC/B injections showed a rapid 19.6 ± 8.0% cell loss during balloon inflation (no-flow period, phase 1) and a rapid 36.6 ± 17.8% cell loss after balloon deflation (re-flow period, phase 2). After each of four consecutive IC/noB injections the peak cell deposit was lower, followed by one phase of rapid cell loss (30.9 ± 11.0% after 6 min). After IM injection only a slow linear cell loss was observed (9.7% per h). In histology, PKH-67 labelled cells only rarely had passed the endothelial barrier after 24 h after IC injection, while they were exclusively found in the interstitium after IM injection.
Conclusion: The observation of a similar cell persistence after IC injections with and without balloon occlusion suggests that the balloon procedures currently applied in clinical studies are not necessary for cell deposit. If longer term persistence of cells plays a role for the clinical benefit of cardiac cell therapy, IM injection may be superior to IC applications.
Key Words: Myocardial infarction • Cell therapy • Bone marrow cells • Mononuclear cells • Stem cells • Heart • Intracoronary • Intramyocardial • Pig • Organ distribution • Balloon
Both authors contributed equally to this work