| Arteries are dynamic tissues that remodel in response to changing mechanical forces associated with blood flow and pressure. Since a clinically relevant example of mechanical regulation of arterial function occurs in bypass graft failure at distal anastomosis sites, an in vivo model of distal anastomosis was used to test the hypothesis that local hemodynamics influence pathological responses. End-to-side anastomoses of right to left rabbit carotid arteries were performed at acute, intermediate and right angles and the upstream left carotid arteries were ligated to simulate pathological occlusion. Tissue responses were examined in the wall of the recipient vessel opposite the anastomosis site (the bed), where unusual hemodynamic forces are imposed. Three months after surgery, intimal thickening was observed on upstream portions of acute, and more rarely, intermediate anastomoses only. Medial thinning due to loss of cells and matrix, and aneurysmal dilatation, was observed in all right angle and some intermediate anastomoses, but not in acute anastomoses. These data illustrate the sensitivity of arterial remodeling to anastomotic angle, presumably through changes in local hemodynamics.; In addition to the mechanical forces associated with blood flow and blood pressure, arteries are also under considerable lengthwise stretch (axial strain); however, the origin, regulation and significance of axial strain has received little study. To test the hypothesis that axial strain greatly influences adaptive remodeling of arterial tissue, rabbit carotid artery responses to both increases and decreases of axial strain were examined. Arteries were surgically stretched, elevating axial strain from 62 ± 2% to 97 ± 2%, without altering blood flow rate. A rapid growth response involving both cell and matrix turnover returned axial strain to basal levels within one week, via an endothelium, independent mechanism. In converse experiments, axial strain was reduced from 62 ± 2% to 30 ± 2% without affecting blood flow rate, by the use of interposition arterial grafts. Axial strain remained unaltered after 12 weeks and extreme vessel tortuosity was evident by 5 weeks. These data indicate that normal axial strains are re-established after increases but not decreases in strain. This thesis provides insight into the physiological regulation of axial strain and the pathological consequences regarding its loss. |
