Modulation of collateral artery growth in a porcine hindlimb ligation model using MCP-1.
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 microg/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 x min(-1) x mmHg(-1) after 2 wk of infusion with PBS, compared with 1,070 +/- 530 and 1,158 +/- 535 ml x min(-1) x mmHg(-1) 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.
Voskuil
Michiel
M
Department of Cardiology, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.
van Royen
Niels
N
Hoefer
Imo E
IE
Seidler
Randolph
R
Guth
Brian D
BD
Bode
Christoph
C
Schaper
Wolfgang
W
Piek
Jan J
JJ
Buschmann
Ivo R
IR
D000792:Angiography; D000818:Animals; D001158:Arteries / Q000254:growth & development*; D001783:Blood Flow Velocity; D001794:Blood Pressure; D018932:Chemokine CCL2 / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D005263:Femoral Artery / Q000601:surgery*; D006614:Hindlimb / Q000098:blood supply*; D007261:Infusions, Intra-Arterial; D008026:Ligation; D008297:Male; D009000:Monocytes; D009131:Muscle, Smooth, Vascular / Q000166:cytology; D009504:Neutrophils; D013552:Swine; D013556:Swine, Miniature
D018932:Chemokine CCL2