Short-term intra-arterial infusion of monocyte chemoattractant protein-1 results in sustained collateral artery growth.
Monocyte chemoattractant protein-1 (MCP-1) is a stimulator of collateral artery growth and has been shown to increase collateral artery conductance in rabbits and pigs. The minimal infusion duration and the minimally effective dose of MCP-1 are currently unknown, as is the sustainability of the therapeutic effect over a longer observation period than tested before. MCP-1 was infused intra-arterially in pigs after unilateral femoral artery occlusion in different doses and infusion durations between 2 hours and 2 weeks. Two weeks after ligation, arterial conductance under maximal vasodilatation was measured. The long-term efficacy was investigated in 2 additional groups of animals after 6 weeks. Infusion with 2 microg/min of MCP-1 for 6 hours was sufficient to double arterial conductance, and arterial conductance after 6 weeks was still significantly increased.
Seidler
Randolph W
RW
Department of Cardiovascular Disease, Boehringer Ingelheim Pharmaceuticals Inc., 900 Ridgebury Road, Ridgefield, CT 06877, USA. rseidler@rdg.boehringer-ingelheim.com
Lenter
Martin C
MC
Guth
Brian D
BD
Doods
Henri
H
D000818:Animals; D001158:Arteries / Q000187:drug effects* / Q000254:growth & development / Q000503:physiopathology; D016466:CHO Cells; D018932:Chemokine CCL2 / Q000008:administration & dosage / Q000235:genetics / Q000494:pharmacology*; D003097:Collateral Circulation / Q000187:drug effects; D006224:Cricetinae; D003412:Cricetulus; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D005263:Femoral Artery / Q000601:surgery; D006801:Humans; D007261:Infusions, Intra-Arterial; D008026:Ligation / Q000009:adverse effects; D008297:Male; D016491:Peripheral Vascular Diseases / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D054390:Receptors, CCR2; D019707:Receptors, Chemokine / Q000235:genetics / Q000502:physiology; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D013552:Swine; D013556:Swine, Miniature; D013997:Time Factors; D016896:Treatment Outcome
C515334:CCR2 protein, human; D018932:Chemokine CCL2; D054390:Receptors, CCR2; D019707:Receptors, Chemokine; D011994:Recombinant Proteins