A modified rat model of hindlimb ischemia for augmentation and functional measurement of arteriogenesis.

Ryan M Mcenaney,Edith Tzeng,Dylan Mccreary

doi:10.14440/jbm.2018.234

Abstract

Arteriogenesis (collateral artery development) is an adaptive pathway critical for salvage of tissue in the setting of arterial occlusion. Rodent models of arteriogenesis typically involve an experimental occlusion (ligation) of a hindlimb artery and then rely on indirect measures such as laser Doppler perfusion imaging to assess blood flow recovery. Unfortunately, the more commonly utilized measures of distal tissue perfusion at rest are unable to account for hemodynamic and vasoactive variables and thus provide an incomplete assessment of collateral network capacity. We provide a detailed description of modifications to the commonly used model of femoral artery ligation. These serve to alter and then directly assess collateral network’s hemodynamic capacity. By incorporating an arteriovenous fistula distal to the arterial ligation, arterial growth is maximized. Hindlimb perfusion may be isolated to measure minimum resistance of flow around the arterial occlusion, which provides a direct measure of collateral network capacity. Our results reinforce that arteriogenesis is driven by hemodynamic variables, and it can be reliably augmented and measured in absolute terms. Using these modifications to a widely used model, functional arteriogenesis may be more directly studied.

Highlights

Arteriogenesis is the natural process of collateral artery development which occurs in response to flow limiting arterial occlusive disease
Laser Doppler perfusion imaging (LDPI) consistently demonstrated that the limb with both a femoral artery ligation (FAL) and a patent arteriovenous fistula (AVF) have much less perfusion to the foot compared with the hindlimb recovering from FAL only (Fig. 2C)
Once selective ligation of the AVF is performed, perfusion to the paw is significantly greater on the limb with the “trained” collateral vessels (Fig. 2C-2D)

Summary

Introduction

Arteriogenesis is the natural process of collateral artery development which occurs in response to flow limiting arterial occlusive disease. Individuals challenged with such occlusions would suffer profound ischemia of brain, myocardium, skeletal muscle and abdominal viscera. Despite the importance of spontaneously formed collateral arteries, they fail to completely restore the blood flow capacity that is lost with large artery occlusion [1,2]. Arteriogenesis has been demonstrated to have potential for increasing collateral network capacity beyond what is spontaneously achieved, these studies have required use of large animal models [5,6]. If therapies to stimulate enhanced arteriogenesis (beyond the spontaneous collateralization) could be identified, a much needed medical alternative to surgical revascularization for patients suffering from arterial insufficiency may be found

Methods

Results

Conclusion