Measurement of strain induced responses at femoral artery bypass graft junctions

Femoral artery bypass grafts have a predilection for failure at the distal anastomosis due to restenosis, within a short period of time, the cause of which has been attributed to altered haemodynamics. This study proposes that pressure induced strain has a profound effect on the endothelium surrounding the junction leading to the onset of stenosis. It is hypothesised that the cellular response in the non-physiological distal junction of a femoral bypass graft can be predicted by measuring the strain response and that this strain response is caused primarily by the intramural pressure. The vascular endothelium represents a highly effective fluid and solute barrier through the synchronised apposition of tight junction protein complexes between adjoining endothelial cells. As endothelial cell mediated functions and pathology are sensitive to mechanical and haemodynamic forces (cyclic strain and shear stress) the author hypothesises that the primary factor responsible for the onset of atherosclerosis surrounding femoral artery bypass grafts is blood pressure as opposed to blood flow. This theory is investigated via the direct measurement of in vivo deflections following elective femoral bypass surgery and the subsequent examination of the precise effects of the recorded cyclic strain versus physiological flow induced shear stress on human aortic endothelial cells (HAEC’s) cultured in vitro, at 12, 24 and 36 hour time intervals. Overall the findings indicate that physiological cyclic strain and shear instigate positive responses such as improved cell turnover and reduced apoptosis. These events were accompanied by a strain-dependent reduction in transendothelial permeability to FITCdextran, an event that indicates improved barrier function. However the strain induced upon the introduction of a synthetic arterial bypass, although close to the normal physiological range, induced negative responses with subsequent consequences for barrier integrity, cell turnover and unprogrammed cell death.