Time course of arteriogenesis following femoral artery occlusion in the rabbit

Objective: We examined the time course of arteriogenesis (collateral artery growth) after femoral artery ligation and the effect of monocyte chemoattr actant protein-1 (MCP-1. Methods: New Zealand White rabbits received MCP-1 or phosphate buffered saline (PBS) for a 1-week period, either directly or 3 weeks after femoral artery ligation (non-ischemic model). A control group was studied with intact femoral arteries and another 1 min after acute fem oral artery ligation. Results: Collateral conductance index significantly i ncreased when MCP-1 treatment started directly after femoral artery ligatio n (acute occlusion: 0.94+/-0.19; without occlusion: 168.56+/-15.99; PBS: 4. 10+/-0.48; MCP-1: 33.96+/-1.76 ml/min/100 mmHg). However, delayed onset of treatment 3 weeks after ligation and final study of conductance at 4 weeks showed no significant difference against a 4-week control (PBS: 79.08+/-7.2 43 MCP-1: 90.03+/-8.73 ml/min/100 mmHg). In these groups increased conducta nce indices were accompanied by a decrease in the number of visible collate ral vessels (from 18 to 36 identifiable vessels at day 7 to about four at 2 1 days). Conclusion: We conclude that the chemokine MCP-1 markedly accelera ted collateral artery growth but did not alter its final extent above that reached spontaneously as a function of time. We show thus for the first tim e that a narrow time window exists for the responsiveness to the arteriogen ic actions of MCP-1. a feature that MCP-1 may share with other growth facto rs. We show furthermore that the spontaneous adaptation by arteriogenesis s tops when only about 50% of the vasodilatory reserve of the arterial bed be fore occlusion are reached. The superiority of few large arterial collatera ls in their ability to conduct large amounts of blood flow per unit of pres sure as compared to the angiogenic response where large numbers of small ve ssels are produced with minimal ability to allow mass transport of bulk flo w is stressed. (C) 2001 Elsevier Science B.V. All rights reserved.