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Improvement of Outcome for Treatment of ‘Restenosis-prone’ Vascular Lesions? Potential Impact of the Paclitaxel dose on Late Lumen Loss in Porcine Peripheral Arteries

PURPOSE: Clinical data indicate that the drug density on drug-coated balloons (DCBs) might have a role on treatment effect and durability. The aim of the current study was to investigate inhibition of neointimal formation and potential adverse effects after treatment with a novel double-dose DCB in...

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Autores principales: Gemeinhardt, Ole, Haase, Tobias, Schnorr, Beatrix, Xie, Jing, Löchel, Melanie, Schütt, Denise, Mittag, Antje, Haider, Wolfram, Bettink, Stephanie, Speck, Ulrich, Tepe, Gunnar
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer US 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9705460/
https://www.ncbi.nlm.nih.gov/pubmed/36109387
http://dx.doi.org/10.1007/s00270-022-03277-x
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author Gemeinhardt, Ole
Haase, Tobias
Schnorr, Beatrix
Xie, Jing
Löchel, Melanie
Schütt, Denise
Mittag, Antje
Haider, Wolfram
Bettink, Stephanie
Speck, Ulrich
Tepe, Gunnar
author_facet Gemeinhardt, Ole
Haase, Tobias
Schnorr, Beatrix
Xie, Jing
Löchel, Melanie
Schütt, Denise
Mittag, Antje
Haider, Wolfram
Bettink, Stephanie
Speck, Ulrich
Tepe, Gunnar
author_sort Gemeinhardt, Ole
collection PubMed
description PURPOSE: Clinical data indicate that the drug density on drug-coated balloons (DCBs) might have a role on treatment effect and durability. The aim of the current study was to investigate inhibition of neointimal formation and potential adverse effects after treatment with a novel double-dose DCB in swine. MATERIAL AND METHODS: A four-week study was performed in peripheral arteries of 12 domestic pigs after vessel injury and stent implantation. The novel double-dose DCB with 6-µg paclitaxel (Ptx)/mm(2) balloon surface (1 × 6) was compared to a standard DCB with 3.5 µg Ptx/mm(2) (3.5) and uncoated balloons (POBA). Potential adverse effects were stimulated by using three fully overlapping DCBs with 6 µg Ptx/mm(2) each (3 × 6). Quantitative angiography, histomorphometry and histopathological analyses were performed. RESULTS: Higher paclitaxel doses per square millimeter of treated arteries were associated with reduced late lumen loss (LLL) in quantitative angiography 4 weeks after treatment (POBA: 0.91 ± 0.75 mm; 3.5: 0.45 ± 0.53 mm; 1 × 6: 0.21 ± 0.41 mm; 3 × 6: − 0.38 ± 0.65 mm). In histomorphometry, maximal neointimal thickness and neointimal area were the lowest for the 1 × 6 group (0.15 ± 0.06 mm/1.5 ± 0.4 mm(2)), followed by 3 × 6 (0.20 ± 0.07 mm/1.8 ± 0.4 mm(2)), 3.5 (0.22 ± 0.12 mm/2.2 ± 1.1 mm(2)) and POBA (0.30 ± 0.07 mm/3.2 ± 0.7 mm(2)). Downstream tissue showed histopathological changes in all groups including POBA, in larger number and different quality (e.g., edema, inflammation, vessel wall necrosis, vasculitis and perivasculitis) in the 3 × 6 group, which did not cause clinical or functional abnormalities throughout the study. CONCLUSION: Treatment with the double-dose DCB (6 µg Ptx/mm(2)) tended to increase inhibition of in-stent neointimal formation and to diminish LLL after peripheral intervention in the porcine model compared to a market-approved DCB with 3.5 µg Ptx/mm(2). SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00270-022-03277-x.
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spelling pubmed-97054602022-11-30 Improvement of Outcome for Treatment of ‘Restenosis-prone’ Vascular Lesions? Potential Impact of the Paclitaxel dose on Late Lumen Loss in Porcine Peripheral Arteries Gemeinhardt, Ole Haase, Tobias Schnorr, Beatrix Xie, Jing Löchel, Melanie Schütt, Denise Mittag, Antje Haider, Wolfram Bettink, Stephanie Speck, Ulrich Tepe, Gunnar Cardiovasc Intervent Radiol Laboratory Investigation PURPOSE: Clinical data indicate that the drug density on drug-coated balloons (DCBs) might have a role on treatment effect and durability. The aim of the current study was to investigate inhibition of neointimal formation and potential adverse effects after treatment with a novel double-dose DCB in swine. MATERIAL AND METHODS: A four-week study was performed in peripheral arteries of 12 domestic pigs after vessel injury and stent implantation. The novel double-dose DCB with 6-µg paclitaxel (Ptx)/mm(2) balloon surface (1 × 6) was compared to a standard DCB with 3.5 µg Ptx/mm(2) (3.5) and uncoated balloons (POBA). Potential adverse effects were stimulated by using three fully overlapping DCBs with 6 µg Ptx/mm(2) each (3 × 6). Quantitative angiography, histomorphometry and histopathological analyses were performed. RESULTS: Higher paclitaxel doses per square millimeter of treated arteries were associated with reduced late lumen loss (LLL) in quantitative angiography 4 weeks after treatment (POBA: 0.91 ± 0.75 mm; 3.5: 0.45 ± 0.53 mm; 1 × 6: 0.21 ± 0.41 mm; 3 × 6: − 0.38 ± 0.65 mm). In histomorphometry, maximal neointimal thickness and neointimal area were the lowest for the 1 × 6 group (0.15 ± 0.06 mm/1.5 ± 0.4 mm(2)), followed by 3 × 6 (0.20 ± 0.07 mm/1.8 ± 0.4 mm(2)), 3.5 (0.22 ± 0.12 mm/2.2 ± 1.1 mm(2)) and POBA (0.30 ± 0.07 mm/3.2 ± 0.7 mm(2)). Downstream tissue showed histopathological changes in all groups including POBA, in larger number and different quality (e.g., edema, inflammation, vessel wall necrosis, vasculitis and perivasculitis) in the 3 × 6 group, which did not cause clinical or functional abnormalities throughout the study. CONCLUSION: Treatment with the double-dose DCB (6 µg Ptx/mm(2)) tended to increase inhibition of in-stent neointimal formation and to diminish LLL after peripheral intervention in the porcine model compared to a market-approved DCB with 3.5 µg Ptx/mm(2). SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00270-022-03277-x. Springer US 2022-09-15 2022 /pmc/articles/PMC9705460/ /pubmed/36109387 http://dx.doi.org/10.1007/s00270-022-03277-x Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Laboratory Investigation
Gemeinhardt, Ole
Haase, Tobias
Schnorr, Beatrix
Xie, Jing
Löchel, Melanie
Schütt, Denise
Mittag, Antje
Haider, Wolfram
Bettink, Stephanie
Speck, Ulrich
Tepe, Gunnar
Improvement of Outcome for Treatment of ‘Restenosis-prone’ Vascular Lesions? Potential Impact of the Paclitaxel dose on Late Lumen Loss in Porcine Peripheral Arteries
title Improvement of Outcome for Treatment of ‘Restenosis-prone’ Vascular Lesions? Potential Impact of the Paclitaxel dose on Late Lumen Loss in Porcine Peripheral Arteries
title_full Improvement of Outcome for Treatment of ‘Restenosis-prone’ Vascular Lesions? Potential Impact of the Paclitaxel dose on Late Lumen Loss in Porcine Peripheral Arteries
title_fullStr Improvement of Outcome for Treatment of ‘Restenosis-prone’ Vascular Lesions? Potential Impact of the Paclitaxel dose on Late Lumen Loss in Porcine Peripheral Arteries
title_full_unstemmed Improvement of Outcome for Treatment of ‘Restenosis-prone’ Vascular Lesions? Potential Impact of the Paclitaxel dose on Late Lumen Loss in Porcine Peripheral Arteries
title_short Improvement of Outcome for Treatment of ‘Restenosis-prone’ Vascular Lesions? Potential Impact of the Paclitaxel dose on Late Lumen Loss in Porcine Peripheral Arteries
title_sort improvement of outcome for treatment of ‘restenosis-prone’ vascular lesions? potential impact of the paclitaxel dose on late lumen loss in porcine peripheral arteries
topic Laboratory Investigation
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9705460/
https://www.ncbi.nlm.nih.gov/pubmed/36109387
http://dx.doi.org/10.1007/s00270-022-03277-x
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