© 2001 by European Society of Cardiology
Copyright © 2001, European Society of Cardiology
Sustained retention of tetradecylthioacetic acid after local delivery reduces angioplasty-induced coronary stenosis in the minipig
aDepartment of Heart Disease, Haukeland University Hospital, N-5021 Bergen, Norway
bDepartment of Clinical Biochemistry, Haukeland University Hospital, N-5021 Bergen, Norway
cDepartment of Pathology, Haukeland University Hospital, N-5021 Bergen, Norway
dResearch Institute for Internal Medicine, Rikshospitalet, N-0027 Oslo, Norway
eSection of Clinical Immunology and Infectious Disease, Rikshospitalet, N-0027 Oslo, Norway
* Corresponding author. Tel.: +47-55-972-220; fax: +47-55-975-150 rpet{at}haukland.no
Objective: The sulfur containing tetradecylthioacetic acid (TTA) has a profound effect on lipid metabolism and may also exert antioxidant and anti-inflammatory actions and thereby counteract coronary stenosis after angioplasty balloon injury. This study examined the possible modulatory effects of TTA, delivered locally, on coronary stenosis in minipigs and the underlying mechanisms of action. Methods: Coronary balloon angioplasty injury using an oversized balloon was performed to 40 coronary arteries (20 minipigs, Sus Scrofa, Gammelsroed) followed by delivery of placebo or TTA via a local drug delivery balloon catheter. TTA was radiolabelled in four pigs. Quantitative coronary angiography and intracoronary ultrasound (ICUS) were performed before and after injury, and after 4 weeks of follow-up. The arteries were examined with histomorphometry. The antioxidant and anti-inflammatory effects of TTA were examined on LDL oxidation and stimulated release of interleukin (IL)-2 and IL-10 in human peripheral blood mononuclear cells (PBMC), respectively. Results: Radioactive TTA was present in the coronary wall after 4 weeks. Angiographic minimal luminal diameter (mean±S.E.M.) in the placebo and TTA group was 1.3±0.1 vs. 2.2±0.2 mm (P<0.01) at follow-up, stenosis rate was 55 and 20% (P<0.01). Remodeling was –0.56±0.12 in the TTA group and –1.28±0.09 in the placebo group (P<0.01). TTA significantly prolonged the lag time of LDL oxidation. In phytohemagglutinin stimulated PBMC, TTA significantly decreased IL-2 levels and increased IL-10 levels suggesting a marked anti-inflammatory net effect. Conclusions: Local delivery of TTA reduces coronary artery stenosis after PTCA as assessed by both angiographic, histomorphometric and ICUS examinations by influencing vessel remodeling rather than intimal hyperplasia. The underlying mechanism(s) seem to involve antioxidant and anti-inflammatory effects of this fatty acid analogue.
KEYWORDS Angioplasty; Arteries; Coronary disease; Infection/inflammation