From Cell Biology to Tissue Engineering


Reduced histologic neo in-stent restenosis after use of a paclitaxel-coated cutting balloon in porcine coronary arteries

Denise Traxler1, Rayyan Hemetsberger2, Andreas Spannbauer1, Katrin Zlabinger1, Alfred Gugerell1, Dominika Lukovic1, Ljubica Mandic1, Noemi Pavo1, Johannes Winkler1 and Mariann Gyöngyösi1

1Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria and 2Internal Medicine I - Cardiology, Nephrology, Intensive Care and Rhythmology, St. Johannes Hospital Dortmund, Dortmund, Germany

Offprint requests to: Mariann Gyöngyösi, MD, PhD, FESC, Department of Cardiology, Medical University of Vienna, Währinger Gürtel 18-20, 1900 Vienna, Austria. e-mail: mariann.gyongyosi@meduniwien.ac.at

Summary. The incidence of in-stent restenosis (ISR) has declined dramatically, but once it develops, no current treatment option, such as drug-eluting stents, drug-coated balloons, or cutting balloons (CBs), prevents re-narrowing of the stented atherosclerotic artery. In this preclinical study, we aimed to improve the efficacy of ISR treatment by coating CBs with paclitaxel (paclitaxel-eluting cutting balloon; PECB) and to characterize the histological features of neo-ISRs that arise after ISR treatment. ISR was induced by bare metal stent (BMS) implantation in coronary arteries in pigs. After one month of follow-up, BMS-induced ISR was treated with either CB or PECB. After another month, we performed quantitative coronary angiography, explanted the treated arteries and assessed histopathological and histomorphometric parameters. In addition, we compared histological features of neo-ISRs with pre-treatment ISRs. Injury, inflammation, fibrin deposition, and endothelialization scores were similar between the CB and PECB groups at one month after ISR treatment. Neointimal area (0.87±0.61 vs. 1.95±1.14 mm2, p=0.02), mean neointimal thickness (0.40±0.39 vs. 0.99±0.56 mm, p=0.01), and percent area stenosis (27.3±20.4 vs. 48.3±22.9%, p=0.04) were decreased in PECB-treated coronary arteries compared to CB-treated arteries, respectively. Density of cells (predominantly smooth muscle cells; SMCs) was increased in neo-ISRs (3.51±3.05×103 vs. 6.35±2.57×103 cells/mm2, p<0.01), but significantly more CD68+ and CD20+ cells were found in pre-treatment ISRs. In conclusion, PECB treatment of ISRs led to better results in terms of smaller neointimal area and %area stenosis of neo-ISR. SMC density was increased in neo-ISRs in contrast with higher percentage of CD68+ and CD20+ cells in pre-treatment ISRs. Histol Histopathol 35, 653-663 (2020)

Key words: Drug-eluting ballon, Cutting balllon, Neointima, In-stent restenosis, Paclitaxel

DOI: 10.14670/HH-18-177