Original Articles
Kinetics of vein graft hyperplasia: Association with tangential stress*,**

Presented at the Fortieth Annual Meeting of the Society for Vascular Surgery, New Orleans, La., June 9-10, 1986.
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Abstract

Vein grafts become thicker as they adapt to arterial circulation, and in large measure this is the consequence of cellular hyperplasia. The kinetics of smooth muscle cell (SMC) and endothelial cell (EC) replication were evaluated in rabbit jugular vein segments transplanted into the carotid arterial circulation to define the role of cell proliferation in this process, and these data were correlated with dimensional changes in grafts from 1 hour to 24 weeks after implantation. At 1 hour most of the perianastomotic endothelium was denuded, as were occasional cells in the graft away from the anastomosis. EC replication (thymidine labeling index) in the center of the graft increased 400 times during the first week and produced an intact endothelial surface by 2 weeks. The EC thymidine index then fell progressively to quiescent pretransplant levels by the twelfth week. SMC replication was maximal at 1 week after grafting and returned to near quiescent levels at 12 and 24 weeks. Graft wall thickness and cross-sectional area reached a maximum at 12 weeks and then remained constant. Deoxyribonucleic acid content exhibited a thirty-five- fold increase in the first 4 weeks, then did not change. Likewise, SMC mass did not increase after 4 weeks. Further increase in cross-sectional wall area between 4 and 12 weeks was accounted for by accumulation of connective tissue. The final ratio of luminal radius to wall thickness decreased to a level equal to that of normal artery. Since blood pressure did not change over the period of the study, this observation supports a possible regulatory role for wall tangential stress in the modification of vein graft structure after transplantation into the arterial circulation. (J VASC SURG 1987;5:126-36.)

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).

. Scanning electron micrographs of vein

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)

  • RL McCann et al.

    Aspirin and dipyridamole decrease intimal hyperplasia in experimental vein grafts

    Ann Surg

    (1980)
  • TB Barrett et al.

    Expression of the sis gene by endothelial cells in culture and in vivo

    Proc Natl Acad Sci USA

    (1984)
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      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.

    **

    Reprint requests: Robert M. Zwolak, M.D., Ph.D., Department of Surgery, RF-25, University of Washington School of Medicine, Seattle, WA 98195.

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