Dose-dependent coronary artery intimal thickening after local delivery of the anti-oxidant tetradecylthioacetic acid from stents.

Objective: To examine the in vitro uptake and elution of the anti-oxidant tetradecylthioacetic acid (TTA) from phosphorylcholine (PC)-coated stents, and the in vivo uptake, retention, inflammatory response and histomorphometric changes after overstretch injury of the porcine coronary artery.

Methods: PC-coated stents were loaded in one of three different concentrations of TTA (87, 174 and 347 mmol/L, i.e. 25, 50 and 100 mg/mL) and randomized versus PC-coated stents to the right coronary or left circumflex artery (18 pigs). Uptake of TTA into the coronary wall from the 347 mmol/L concentration was measured after 3 h and 24 h, 7 days, 14 days and 28 days (two pigs at each time point).

Results: In vitro, TTA was successfully loaded onto the stents and elution was nearly complete after 48 h. In vivo, TTA could be demonstrated in the vessel wall for up to 4 weeks. Percent area stenosis was significantly higher in the TTA group, 35.2+/-20.9% versus 27.5+/-17.0% (p=0.03). Dose-related comparison showed increased intimal thickness, 0.66+/-0.53 mm versus 0.29+/-0.26 mm (p=0.008) and intimal area, 2.83+/-1.61 mm2 versus 1.58+/-0.91 mm2 (p=0.004) for the 347 mmol/L TTA versus controls. There was a significantly positive relationship between the TTA-loading dose and both intimal area (B=0.69, p=0.01) and maximal intimal thickness (B=0.17, p=0.02). The pro-inflammatory precursor arachidonic acid increased four-fold in the arterial wall of the TTA group, while the anti-inflammatory fatty acid index, calculated as (docosapentaenoic acid+docosahexaenoic acid+dihomo-linolenic acid)/arachidonic acid, was suppressed to 0.65+/-0.27 compared to 1.13+/-0.23 in control vessels (p<0.001).

Conclusion: TTA caused a dose-dependent intimal thickening and reduced anti-inflammatory fatty acid index. Contrary to expectations, TTA seems unsuitable as stent coating.