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1 Department of Cardiology, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands; 2 Research Group for Experimental and Clinical Arteriogenesis at the Department for Cardiology and Angiology, Albert-Ludwigs University Freiburg, D-79106 Freiburg; 3 Boehringer Ingelheim Pharma KG, D88397 Biberach; and 4 Max-Planck-Institute for Experimental Cardiology, D-61231 Bad Nauheim, Germany
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 hindlimb ligation model. In 40 minipigs, a femoral artery
ligation was performed. Control animals were examined immediately after
ligation (n = 4) or after 2 wk of intra-arterial
infusion of PBS (n = 11). A second group of animals was
evaluated after intra-arterial infusion of 2.0 µg/h of MCP-1 for
48 h (followed by 12 days of PBS; n = 13) or 2 wk
continuously (n = 12). In the terminal experiment after
2 wk, resting flow to the leg and peripheral arterial pressures were
assessed without vasodilatation. Subsequently, vascular conductance was
determined by using a pump-driven extracorporal circulation during
maximal vasodilatation. The results showed that resting blood flow to
the hindlimb was 53% of the normal after 2 wk of infusion of PBS,
compared with 81% in both MCP-1 treatment groups (P < 0.05). Collateral conductance was 645 ± 346 ml · min
1 · mmHg1
after 2 wk of infusion with PBS, compared with 1,070 ± 530 and 1,158 ± 535 ml · min1 · mmHg1
after 48 h and 2 wk 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 Cys-Cys-chemokine MCP-1.
peripheral arterial obstructive disease; intervention; growth factor
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