Biological effect of orbital atherectomy and adjunctive paclitaxel-coated balloon therapy on vascular healing and drug retention: early experimental insights into the familial hypercholesterolaemic swine model of femoral artery stenosis.

AIMS: The efficacy of paclitaxel-coated balloons (PCB) for the treatment of superficial femoral artery (SFA) disease has been demonstrated in the clinical setting. Due to the high frequency of arterial calcification found in this vascular territory, the adjunctive use of atherectomy plus PCB has been proposed. In this study, we aimed to evaluate the biological effect on vascular healing and drug retention of this combination approach in the familial hypercholesterolaemic swine (FHS) model of femoral artery stenosis. METHODS AND RESULTS: Eleven femoral arteries (six superficial and five profunda arteries) were included. Vessels were injured (x2) over a 28-day period and all animals were maintained on a high cholesterol diet for 60 days following initial injury. Vessels were randomised to PCB (n=5) or orbital atherectomy system (OAS) plus PCB (n=6). At 28 days following therapy, vessels were followed with angiography, intravascular ultrasound (IVUS) and optical coherence tomography (OCT). Vessels were harvested for histological and pharmacokinetic analysis. Angiographic findings were comparable at termination between both groups. The OCT findings were comparable at termination. There were no differences in the vascular healing profile between both groups. The paclitaxel levels at termination were comparable between both groups (PCB=5.16 vs. OAS+PCB=3.03 ng/mg). CONCLUSIONS: In the experimental setting, the combination of OAS+PCB appears to be safe by demonstrating a vascular healing profile and drug tissue levels comparable to PCB only. The vascular effect of PCB may be enhanced by the use of OAS by decreasing plaque burden and cholesterol crystals.

Renal artery nerve distribution and density in the porcine model: biologic implications for the development of radiofrequency ablation therapies.

Catheter-based renal artery denervation has demonstrated to be effective in decreasing blood pressure among patients with refractory hypertension. The anatomic distribution of renal artery nerves may influence the safety and efficacy profile of this procedure. We aimed to describe the anatomic distribution and density of periarterial renal nerves in the porcine model. Thirty arterial renal sections were included in the analysis by harvesting a tissue block containing the renal arteries and perirenal tissue from each animal. Each artery was divided into 3 segments (proximal, mid, and distal) and assessed for total number, size, and depth of the nerves according to the location. Nerve counts were greatest proximally (45.62% of the total nerves) and decreased gradually distally (mid, 24.58%; distal, 29.79%). The distribution in nerve size was similar across all 3 sections (∼40% of the nerves, 50-100 µm; ∼30%, 0-50 µm; ∼20%, 100-200 µm; and ∼10%, 200-500 µm). In the arterial segments ∼45% of the nerves were located within 2 mm from the arterial wall whereas ∼52% of all nerves were located within 2.5 mm from the arterial wall. Sympathetic efferent fibers outnumbered sensory afferent fibers overwhelmingly, intermixed within the nerve bundle. In the porcine model, renal artery nerves are seen more frequently in the proximal segment of the artery. Nerve size distribution appears to be homogeneous throughout the artery length. Nerve bundles progress closer to the arterial wall in the distal segments of the artery. This anatomic distribution may have implications for the future development of renal denervation therapies.