Rationale and practical techniques for mouse models of early vein graft adaptations

Abstract

Mouse models serve as relatively new yet powerful research tools to study intimal hyperplasia and wall remodeling of vein bypass graft failure. Several model variations have been reported in the past decade. However, the approach demands thoughtful preparation, selected sophisticated equipment, microsurgical technical expertise, advanced tissue processing, and data acquisition. This review compares several described models and aims (building on our personal experiences) to practically aid the investigators who want to utilize mouse models of vein graft failure.

Copyright (c) 2010 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.

Figures

Fig 1

Cuff-technique mouse vein graft model. A. An example rodent survival operating suite with operating microscope and table-top small animal anesthesia system. B. Schematic representation of the cuff-technique vein bypass graft model. C. Two everted and secured carotid artery ends. D. Completed mouse carotid interposition vein graft. E. Hand-made PEEK anastomotic cuff with handle.

Fig 2

Mouse carotid artery anatomy and partial ligation methods (A, Photographed right carotid anatomy (cut surgical glove background). B, Schematic representation). a, Right common carotid artery. b, Internal carotid artery. c, External carotid artery. d, Occipital artery. e, Superior thyroid artery. (1), Ligation of external carotid artery, including superior thyroid artery, but not occipital artery. (2), Ligation of internal carotid artery. (3), Ligation of internal carotid artery plus occipital artery.

Fig 3

Masson trichrome staining (A–F) and α-actin immunohistochemistry staining (G, H) of cross-sections of mouse vein grafts/vein. Black arrows depict the internal elastic lamina (A–D, F–H); red arrows show the tunica adventitia/peri-vascular tissue boundary (A–D); and green arrows show the vasa vasorum (H). A, Normal flow vein graft at day 28. B, Vein graft with distal arterial partial (internal carotid + occipital artery) ligation at day 28. C, Vein graft with distal arterial partial (external carotid + internal carotid) ligation (leaving the occipital artery patent) at day 14. D, Negative wall remodeling in a mouse vein graft at day 28. E, Normal IVC. F, Enlarged area defined by the black box of Fig 3E. G (normal IVC) and H (mouse vein graft at day 28), note some rose-red or brownish-red positive expression of α-actin in the tunica media (beyond the internal elastic lamina).

Fig 4

Masson trichrome staining of two longitudinally sectioned mouse vein grafts (cuff-technique, cuffs were removed at ends, leading to artifact). Note variations in intimal thickness along the length of the graft.

Fig 5

Upper left Duplex ultrasound scanning of mouse right carotid vein graft model (cuff-technique), taken by Vevo 2100 Imaging System (VisualSonics Inc., Toronto, Canada). Red arrows show vein graft wall. Lower: Velocity of vein graft blood flow.