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±0.53mm versus 0.29±0.26mm (p = 0.008) and intimal
area, 2.83±1.61mm2 versus 1.58±0.91mm2 (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. |
