Abstract 270: Acute Reductions in Wall Strain Precede Formation of Intimal Hyperplasia

Intimal hyperplasia (IH) remains the major culprit in revascularization failures. We aimed to unravel relationships between acute changes in circumferential arterial wall strain and genesis of IH. Methods To induce IH, we employed a validated model using a 9-0 nylon suture tie around the distal mouse common carotid artery (n=10) and an external 35-gauge needle mandrel (OD=0.14mm), with subsequent removal of the mandrel to create a distal common carotid focal stenosis (~78% lumen diameter/~85% flow reduction). Wall strains were measured in three, 1 mm wide regions along the vessel proximal to the focal stenosis at pre-op day 1 and at post-op day 4 (before detectable IH) using Vevo 2100 ultrasonography with VevoVasc software. At post-op day 28, arteries were perfusion fixed and IH was assessed in the same regions as those where strain was analyzed. Strain and morphology were also assessed in the contralateral control artery. Results Decreased wall strain was noted in all regions proximal to the focal stenosis from 0.26 ± 0.01 to 0.11 ± 0.02 (p 0.1. All segments (n = 13) with wall strain ≤0.1 at post-op day 4 had significant IH at day 28. In regions with strains >0.1 at day 4, only 30% had IH at day 28. The average pre-op strains were identical in >0.1 and ≤0.1 strain groups (0.27 ± 0.09 and 0.27 ± 0.08). Mean intimal thickness in vessels with strain ≤0.1 was 32 ± 20 μm, significantly greater than 8.0 ± 16 μm in the group with strain >0.1 (p 0.1 and ≤0.1 groups remained unchanged from pre-op to post-op day 4 (p=0.46), diastolic area was significantly increased in regions with post-op day 4 strain ≤0.1 (p=0.04) but remained unchanged in mice with post-op day 4 strain >0.1 (p=0.67). Conclusions Acute reduction in wall strain precedes the formation of IH in this murine model and this change is primarily caused by an increase in diastolic lumen area. Manipulations of wall strain offer a strategy to prevent and attenuate occlusive IH lesions after revascularizations.