A simple fluid-structure coupling algorithm for the study of the anastomotic mechanics of vascular grafts.

Vascular anastomoses constitute a main factor in poor graft performance due to mismatches in distensibility between the host artery and the graft. This work aims at computational fluid-structure investigations of proximal and distal anastomoses of vein grafts and synthetic grafts. Finite element and finite volume models were developed and coupled with a user-defined algorithm. Emphasis was placed on the simplicity of the coupling algorithm. An artery and vein graft showed a larger dilation mismatch than an artery and synthetic graft. The vein graft distended nearly twice as much as the artery while the synthetic graft displayed only approximately half the arterial dilation. For the vein graft, luminal mismatching was aggravated by development of an anastomotic pseudo-stenosis. While this study focused on end-to-end anastomoses as a vehicle for developing the coupling algorithm, it may serve as useful point of departure for further investigations such as other anastomotic configurations, refined modelling of sutures and fully transient behaviour.

Effect of gamma-irradiation and bone marrow transplantation on atherosclerosis in LDL receptor-deficient mice.

Bone marrow transplantation (BMT) is commonly used to study the participation of bone marrow-derived cells in atherosclerosis. To determine the effect of this methodology on lesions, 16 male low density lipoprotein (LDL) receptor knockout (LDLr-/-) mice were reconstituted with bone marrow from syngeneic LDLr-/- mice after 10 Gy gamma-irradiation and compared with 12 male LDLr-/- littermates that did not undergo BMT (no-BMT group). Mice were fed a high fat diet (HFD) for 16 weeks to induce atherosclerosis. Sixteen additional LDLr-/- mice underwent BMT, and 12 male LDLr-/- mice that did not undergo BMT were fed a chow diet for 56 weeks. Thoracic aorta lesion areas were smaller in BMT mice than in no-BMT mice fed the HFD (P<0.0001). In contrast, aortic root lesion areas were greater in the BMT mice fed the HFD (P<0.0001) as well as in those fed the chow diet (P=0.0001). Abdominal aorta free cholesterol and cholesteryl ester mass were minimal in all groups studied. Aortic root lesions from all no-BMT mice were densely collagenous and encapsulated by a cellular cap, whereas lesions in the BMT mice contained lipid cores and minimal collagen staining. Although the reason for these differences in lesion size and composition remains unresolved, this study suggests that multiple parameters of lesion formation should be examined to assess atherosclerosis.

Participation of innate and acquired immunity in atherosclerosis.

Coronary artery disease, the major manifestation of atherosclerosis, is the leading cause of death in the Western world. However, the pathogenesis of atherosclerosis is still poorly understood. Controversy exists regarding the participation of innate immunity involving macrophages and natural killer (NK) cells vs antigen-specific acquired immunity involving lymphocytes. Macrophages predominate in atherosclerotic lesions. NK cells, although smaller in number, are present as well. Furthermore, T lymphocytes that participate in acquired immunity are frequently observed in lesions and can modulate lesion progression. By using mouse models of hyperlipidemia, our laboratory is addressing in vivo the participation of both innate inflammatory responses and acquired immune responses in atherosclerosis.

Endothelial cell regrowth and morphology after balloon catheter injury of alloxan-induced diabetic rabbits.

Neointimal thickening after catheter injury has been reported to be influenced by the integrity of the vascular endothelium. We have previously shown that neointimal thickening is significantly reduced in alloxan-induced diabetic New Zealand White rabbits after catheter injury compared with euglycemic rabbits. In the present study, it was hypothesized that endothelial cell regrowth, morphology, and endothelium-dependent vasoreactivity after catheter injury are improved in the diabetic rabbit (glucose >/=400 mg/dl) compared with the euglycemic rabbit. Two weeks after catheter injury, the percent endothelial regrowth was significantly increased in diabetic animals compared with euglycemic animals (32.1 +/- 2 and 15.6 +/- 1, respectively; P < 0.05). The endothelial cell morphology analyzed by scanning electron microscopy was also restored 2 wk after catheter injury in thoracic aortas from the diabetic animals compared with vessels from euglycemic animals. Endothelium-dependent relaxation to ACh in vessels from diabetic and euglycemic rabbits was attenuated 2 wk after injury, and, although improved by 4 and 8 wk, relaxation remained significantly depressed. These results suggest that endothelial cell regrowth and morphology in diabetic animals was improved compared with euglycemic animals; however, endothelium-dependent vasoreactivity remained impaired. Thus the attenuated neointimal thickening seen in the diabetic rabbit may be a function of the rate and degree of regrowth rather than the normalization of ACh-induced relaxation.

Balloon catheter vascular injury of the alloxan-induced diabetic rabbit: the role of insulin-like growth factor-1.

Neointimal thickening following catheter injury is characterized, in part, by growth factor-induced vascular smooth muscle cell (VSMC) proliferation. It was hypothesized that a reduction in serum insulin-like growth factor-1 (IGF-1), characteristic of chemically-induced diabetes, would result in decreased VSMC proliferation and attenuate neointimal thickening. It was found that alloxan-treated New Zealand White rabbits exhibit varying degrees of glycemia. Rabbits classified as diabetic (glucose > or = 400 mg/dL) had significantly decreased serum concentration of IGF-1 (87.4+/-14 nmol/L vs. 170+/-14 nmol/L) and significantly decreased intimal/medial (I/M) ratios 2, 4, and 8 weeks after aortic injury compared to euglycemic rabbits (13.7+/-2, 21.1+/-2, 32.4+/-3 in euglycemics and 6.6+/-1, 14+/-2, 19+/-5 in diabetics, respectively). The I/M for high hyperglycemic animals (glucose 286-399 mg/dL) was comparable to diabetic animals yet their serum IGF-1 levels were normal rather than depressed. Vascular IGF-1 content similarly increased upon injury in both diabetic and euglycemic animals. In diabetic animals, proliferating cell nuclear antigen (PCNA) immunostaining was present by day 1 peaked by day 5 and returned to control by day 14. In euglycemic animals, staining by day 1 continued to increase through day 14. A similar increase in mitogen-activated protein kinase (MAPK) activity occurred from day 1 through day 5 in both diabetic and euglycemic animals. This is the first demonstration of an association between MAPK activity and VSMC proliferation following vascular injury in diabetic animals as previously reported in euglycemic animals. In conclusion, this study provides evidence against a direct effect of IGF-1 in the reduction in neointimal thickening, VSMC proliferation, and MAPK activity upon catheter injury in chemically-induced diabetic rabbits.