Intrapericardial paclitaxel delivery inhibits neointimal proliferation and promotes arterial enlargement after porcine coronary overstretch

Dongming Hou, Pamela I. Rogers, Philip M. Toleikis, William Hunter, Keith L. March

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

Background - Catheter-based intrapericardial (IPC) delivery of therapeutic agents has recently been demonstrated. Paclitaxel is known to inhibit vascular smooth muscle cell proliferation. This study examined the effect of IPC instillation of paclitaxel on neointimal proliferation after balloon overstretch of porcine coronary arteries. Methods and Results - Overstretch injury of coronary arteries was followed by IPC administration of micellar paclitaxel at low dose (LD, 10 mg; n=6) or high dose (HD, 50 mg; n=7) or of control micelles (50 mg, n=5). Animals were euthanized 28 days after balloon dilation. Arterial injury indices were no different among the groups. The neointimal area, maximal intimal thickness, and adventitial thickness were significantly reduced in both LD (0.47±0.04 mm2, 0.43±0.03 mm, and 0.35±0.02 mm, respectively) and HD (0.51±0.06 mm2, 0.42±0.03 rnm, and 0.38±0.03 mm, respectively) paclitaxel groups compared with the control group (0.79±0.07 mm2, 0.56±0.02 mm, and 0.47±0.02 mm, respectively; P<0.001). Meanwhile, the vessel circumference measured at the external elastic lamina of paclitaxel-treated vessels was significantly larger than the control circumference. Apoptotic cells were found in the neointima. The apoptotic cell percentage was not different between the control (1.72%) and LD (2.31%) groups but was higher in the HD group (7.07%, P<0.0001 versus control and LD groups). Immunostaining for matrix metalloproteinase-2 revealed concurrent reduction in the HD group compared with the control and LD groups. Conclusions - IPC space delivery of a single dose of paclitaxel significantly reduces vessel narrowing in this balloon-overstretch model. This effect is mediated by reduction of neointimal mass as well as positive vascular remodeling.

Original languageEnglish
Pages (from-to)1575-1581
Number of pages7
JournalCirculation
Volume102
Issue number13
StatePublished - Sep 26 2000

Fingerprint

Paclitaxel
Swine
Control Groups
Coronary Vessels
Tunica Intima
Neointima
Adventitia
Matrix Metalloproteinase 2
Wounds and Injuries
Micelles
Vascular Smooth Muscle
Smooth Muscle Myocytes
Dilatation
Catheters
Cell Proliferation

Keywords

  • Apoptosis
  • Paclitaxel
  • Pericardium
  • Remodeling
  • Restenosis

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Hou, D., Rogers, P. I., Toleikis, P. M., Hunter, W., & March, K. L. (2000). Intrapericardial paclitaxel delivery inhibits neointimal proliferation and promotes arterial enlargement after porcine coronary overstretch. Circulation, 102(13), 1575-1581.

Intrapericardial paclitaxel delivery inhibits neointimal proliferation and promotes arterial enlargement after porcine coronary overstretch. / Hou, Dongming; Rogers, Pamela I.; Toleikis, Philip M.; Hunter, William; March, Keith L.

In: Circulation, Vol. 102, No. 13, 26.09.2000, p. 1575-1581.

Research output: Contribution to journalArticle

Hou, D, Rogers, PI, Toleikis, PM, Hunter, W & March, KL 2000, 'Intrapericardial paclitaxel delivery inhibits neointimal proliferation and promotes arterial enlargement after porcine coronary overstretch', Circulation, vol. 102, no. 13, pp. 1575-1581.
Hou, Dongming ; Rogers, Pamela I. ; Toleikis, Philip M. ; Hunter, William ; March, Keith L. / Intrapericardial paclitaxel delivery inhibits neointimal proliferation and promotes arterial enlargement after porcine coronary overstretch. In: Circulation. 2000 ; Vol. 102, No. 13. pp. 1575-1581.
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abstract = "Background - Catheter-based intrapericardial (IPC) delivery of therapeutic agents has recently been demonstrated. Paclitaxel is known to inhibit vascular smooth muscle cell proliferation. This study examined the effect of IPC instillation of paclitaxel on neointimal proliferation after balloon overstretch of porcine coronary arteries. Methods and Results - Overstretch injury of coronary arteries was followed by IPC administration of micellar paclitaxel at low dose (LD, 10 mg; n=6) or high dose (HD, 50 mg; n=7) or of control micelles (50 mg, n=5). Animals were euthanized 28 days after balloon dilation. Arterial injury indices were no different among the groups. The neointimal area, maximal intimal thickness, and adventitial thickness were significantly reduced in both LD (0.47±0.04 mm2, 0.43±0.03 mm, and 0.35±0.02 mm, respectively) and HD (0.51±0.06 mm2, 0.42±0.03 rnm, and 0.38±0.03 mm, respectively) paclitaxel groups compared with the control group (0.79±0.07 mm2, 0.56±0.02 mm, and 0.47±0.02 mm, respectively; P<0.001). Meanwhile, the vessel circumference measured at the external elastic lamina of paclitaxel-treated vessels was significantly larger than the control circumference. Apoptotic cells were found in the neointima. The apoptotic cell percentage was not different between the control (1.72{\%}) and LD (2.31{\%}) groups but was higher in the HD group (7.07{\%}, P<0.0001 versus control and LD groups). Immunostaining for matrix metalloproteinase-2 revealed concurrent reduction in the HD group compared with the control and LD groups. Conclusions - IPC space delivery of a single dose of paclitaxel significantly reduces vessel narrowing in this balloon-overstretch model. This effect is mediated by reduction of neointimal mass as well as positive vascular remodeling.",
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AU - Hunter, William

AU - March, Keith L.

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AB - Background - Catheter-based intrapericardial (IPC) delivery of therapeutic agents has recently been demonstrated. Paclitaxel is known to inhibit vascular smooth muscle cell proliferation. This study examined the effect of IPC instillation of paclitaxel on neointimal proliferation after balloon overstretch of porcine coronary arteries. Methods and Results - Overstretch injury of coronary arteries was followed by IPC administration of micellar paclitaxel at low dose (LD, 10 mg; n=6) or high dose (HD, 50 mg; n=7) or of control micelles (50 mg, n=5). Animals were euthanized 28 days after balloon dilation. Arterial injury indices were no different among the groups. The neointimal area, maximal intimal thickness, and adventitial thickness were significantly reduced in both LD (0.47±0.04 mm2, 0.43±0.03 mm, and 0.35±0.02 mm, respectively) and HD (0.51±0.06 mm2, 0.42±0.03 rnm, and 0.38±0.03 mm, respectively) paclitaxel groups compared with the control group (0.79±0.07 mm2, 0.56±0.02 mm, and 0.47±0.02 mm, respectively; P<0.001). Meanwhile, the vessel circumference measured at the external elastic lamina of paclitaxel-treated vessels was significantly larger than the control circumference. Apoptotic cells were found in the neointima. The apoptotic cell percentage was not different between the control (1.72%) and LD (2.31%) groups but was higher in the HD group (7.07%, P<0.0001 versus control and LD groups). Immunostaining for matrix metalloproteinase-2 revealed concurrent reduction in the HD group compared with the control and LD groups. Conclusions - IPC space delivery of a single dose of paclitaxel significantly reduces vessel narrowing in this balloon-overstretch model. This effect is mediated by reduction of neointimal mass as well as positive vascular remodeling.

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