Original ArticlesKinetics of vein graft hyperplasia: Association with tangential stress*,**
Section snippets
Methods
An autologous jugular vein graft model was prepared in New Zealand white rabbits weighing 2.8 to 3.2 kg. The rabbits were anesthetized with xylazine (7 mg/kg) and ketamine (35 mg/kg), and the left carotid artery and jugular vein were exposed through a vertical midline neck incision. Heparin (1000 units) was given intravenously, and a 3 cm segment of jugular vein distal to the main branch point and lacking valves was dissected free from surrounding connective tissue. An adjacent section of left
Morphology
Scanning electron microscopy showed a continuous layer of endothelium on the surface of normal vein. Transplantation of jugular vein into the carotid circulation resulted in loss of endothelium primarily at anastomoses. Denuded regions were covered by a carpet of platelets, occasional microthrombi, and leukocytes. At 1 week small patches of denudation were still present, and by 2 weeks the endothelial layer was fully restored in every graft studied (Fig. 1).
Discussion
The data presented provide a quantitative description of the hyperplastic response in vein segments placed in an arterial environment. In this model grafting causes partial endothelial denudation. Endothelial coverage is restored by proliferation of the remaining viable cells and is complete by 2 weeks although labeling activity is still elevated for at least 4 weeks. This may represent replacement of cells injured during a continued nondenuding injury of venous ECs when exposed to arterial
Conclusions
The kinetic data presented in this study suggest that both the EC and the SMC populations survive transplantation and in fact undergo a massive burst of proliferative activity in the 4 weeks after transplantation. Proliferation results in at least a thirty-five-fold increase in DNA expressed per square millimeter of luminal surface area. After 4 weeks, EC and SMC proliferation returns to near quiescent levels, and the continued increase in wall thickness and area relates almost exclusively to
Acknowledgements
We gratefully acknowledge the assistance of Thomas Kirkman, Thomas Opstad, and Monika Clowes in the conduct of these experiments.
References (24)
- et al.
Mechanisms of arterial graft failure. II. Chronic endothelial and smooth muscle cell proliferation in healing polytetrafluoroethylene prostheses
J Vasc Surg
(1986) - et al.
The fluorometric measurement of deoxyribonucleic acid in animal tissues with special reference to the central nervous system
J Biol Chem
(1958) - et al.
Morphologic alteration on cultured arterial smooth muscle cells by cyclic stretching
J Surg Res
(1983) - et al.
Effect of wall shear stress on intimal thickening of arterially transplanted autogenous veins in dogs
J Vasc Surg
(1985) - et al.
Results of the biterminal transplantation of veins
Am J Med Sci
(1906) - et al.
Biologic fate of autogenous vein implants as arterial substitutes
Ann Surg
(1973) - et al.
The relation of risk factors to the development of atherosclerosis in saphenous-vein bypass grafts and the progression of disease in the native circulation
N Engl J Med
(1984) - et al.
Mechanisms of arterial graft failure 1. Role of cellular proliferation in early healing of PTFE prostheses
Am J Pathol
(1985) - et al.
Fibroblast Monolayer cultures in scintillation counting vials: Metabolic and growth experiments using radioisotopes and a microfluorometric DNA assay
In Vitro
(1977) - et al.
Significance of quiescent smooth muscle migration in the injured rat carotid artery
Circ Res
(1985)
Aspirin and dipyridamole decrease intimal hyperplasia in experimental vein grafts
Ann Surg
Expression of the sis gene by endothelial cells in culture and in vivo
Proc Natl Acad Sci USA
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2016, Journal of BiomechanicsCitation Excerpt :Intimal hyperplasia, the precursor lesion for atherosclerosis, is thought to be stimulated by injury, inflammation, and perturbed hemodynamics that affect endothelial shear stress and intramural wall stress. A study of vein grafting hyperplasia clearly demonstrated a relationship between increased mean wall stress and intimal hyperplasia (Zwolak et al., 1987). Choy et al. showed venous hypertension induced by ligation can cause intimal hyperplasia in superficial veins that were not tethered by the myocardium but only wall thickening in intra-myocardial veins due to differences in wall stress in the two local environments of the same heart (Choy et al., 2006).
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Supported by grants HL18645 and HL01108 from the National Institutes of Health, United States Public Health Service.
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Reprint requests: Robert M. Zwolak, M.D., Ph.D., Department of Surgery, RF-25, University of Washington School of Medicine, Seattle, WA 98195.