17 Femoral artery ligation induces rapid arteriogenesis that correlates with recovery of perfusion in the foot

Abstract

Background and hypothesis Reperfusion following acute hindlimb ischaemia is mediated by both arteriogenesis (collateral growth) and angiogenesis. According to Poiseuille’s Law, the arterial ability to conduct blood is proportional to the 4th order of its diameter. This suggests collateral arteries with a relatively large diameter are better suited to conduct blood than smaller vessels. We hypothesise that arteriogenic remodelling of collateral vessels has a greater role than angiogenesis in restoring blood supply to the ischaemic hindlimb. Methods Acute hindlimb ischaemia was induced in 12-week-old male C57BL/6J mice by unilateral femoral artery ligation. Reperfusion in the foot pad was monitored by laser Doppler immediately before and after femoral artery ligation and subsequently on days 1, 3 and 7 (n=3 for each time point). Vascular resin casts plus optical projection tomography (OPT) were used to illustrate the arterial network before and after ischaemia. Results Blood perfusion in the foot pad dropped by ~90% immediately following ligation but exhibited a 40% recovery over the next 7 days. This restoration of flow correlated with the emergence and growth of collateral arteries in the thigh (upstream of the ligation point). Conclusion A pre-existing collateral circulation provides the residual blood supply after femoral ligation. A rapid increase in the diameter of a small number of collateral arteries appeared to be the major mechanism for acute restoration of blood supply to the ischaemic lower leg and foot pad. Future work will use histology and immunohistochemistry to investigate the role of angiogenesis in reperfusion following femoral ligation.