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1 Department of Cardiology, Academic Medical Center, Amsterdam, The Netherlands
2 Department of Cardiology, Academic Medical Center, Amsterdam, The Netherlands; Department of Cardiology, Albert-Ludwigs University, Freiburg, Germany
3 Department of Cardiology, Albert-Ludwigs University, Freiburg, Germany
4 Cardiovascular Research, Boehringer Ingelheim Pharma KG, Biberach, Germany
5 Experimental Cardiology, Max-Planck Institute, Bad Nauheim, Germany
* To whom correspondence should be addressed. E-mail: j.j.piek{at}amc.uva.nl.
For an appropriate extrapolation to patients with peripheral arterial obstructive disease we tested the efficacy of monocyte chemoattractant protein 1 (MCP-1) treatment in a porcine hind limb ligation model. In 40 minipigs, a femoral artery ligation was performed. Control animals was examined immediately after ligation (n = 4), or after two weeks of intra-arterial infusion of phosphate buffered saline (PBS; n = 11). A second group of animals was evaluated after intra-arterial infusion of 2.0 µg/h of MCP-1 for 48 hours (followed by 12 days of PBS; n = 13) or two weeks continuously (n = 12). In the terminal experiment after two weeks, resting flow to the leg and peripheral arterial pressures were assessed, without vasodilatation. Subsequently, vascular conductance was determined using a pump driven extra corporal circulation, during maximal vasodilatation. The results showed that resting blood flow to the hind limb was 53% of normal after two weeks of infusion of PBS, compared to 81% in both MCP-1 treatment groups (P < 0.05). Collateral conductance was 645 ± 346 ml/min/mmHg after two weeks of infusion with PBS, compared to 1070 ± 530 and 1158 ± 535 ml/min/mmHg after 48 hours and two weeks treatment with MCP-1, respectively (P < 0.05). Modulation of the process of arteriogenesis is feasible in this large animal model via intra-arterial infusion of the C-C-chemokine MCP-1.
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