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Pretreatment with intraluminal rapamycin nanoparticle perfusion inhibits neointimal hyperplasia in a rabbit vein graft model.

Liu K, Cao G, Zhang X, Liu R, Zou W, Wu S - Int J Nanomedicine (2010)

Bottom Line: On postoperative day 28, the grafts and normal veins were harvested for histologic examination, flow cytometry analysis, and high-performance liquid chromatography measurement.Compared with Group 1, the intima of the grafts were thickened, the ratio of intimal area to vessel area increased, and the collagen volume index of the vein grafts increased significantly in Groups 2 and 3.The cell proliferation index in Group 1 (21.11 ± 3.15%) was much lower than that in Group 2 (30.35 ± 2.69%) and in Group 3 (33.86 ± 8.72%).

View Article: PubMed Central - PubMed

Affiliation: Department of Cardiovascular Surgery, Qilu Hospital of Shandong University, Jinan, People’s Republic of China.

ABSTRACT

Purpose: Poly lactic-co-glycolic acid nanoparticles (PLGA-NP) are widely used as a biodegradable biomaterial in medicine. Rapamycin-eluting stents have been used for prevention of restenosis during surgery. This study investigated the effect of pretreatment with intraluminal perfusion of carbopol-encapsulated rapamycin-loaded PLGA nanoparticles (RAP-PLGA-NP) on neointimal hyperplasia in a rabbit vein graft model.

Methods: A segment of common carotid artery was replaced with a segment of external jugular vein in 60 rabbits which were then separated into four treatment groups, ie, Group 1, in which vein grafts were pretreated with intraluminal RAP-PLGA-NP perfusion, Group 2 in which vein grafts underwent equivalent empty vehicle (PLGA-NP) perfusion, Group 3, in which vein grafts received no treatment, and Group 4, which served as a sham operation group receiving normal vein contrast. On postoperative day 28, the grafts and normal veins were harvested for histologic examination, flow cytometry analysis, and high-performance liquid chromatography measurement.

Results: Compared with Group 1, the intima of the grafts were thickened, the ratio of intimal area to vessel area increased, and the collagen volume index of the vein grafts increased significantly in Groups 2 and 3. The cell proliferation index in Group 1 (21.11 ± 3.15%) was much lower than that in Group 2 (30.35 ± 2.69%) and in Group 3 (33.86 ± 8.72%). By high-performance liquid chromatography measurement, retention of rapamycin was detected in Group 1 (11.2 ± 0.37 μg/10 mg) 28 days after single drug perfusion.

Conclusion: Pretreatment with intraluminal RAP-PLGA-NP perfusion may inhibit neointimal hyperplasia in vein grafts by penetrating into local tissue and limiting cell proliferation.

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Related in: MedlinePlus

A) Rabbit model of interposition of external jugular vein into the common carotid artery using an end-to-side technique. B) Self-made drug-perfusion device.
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f1-ijn-5-853: A) Rabbit model of interposition of external jugular vein into the common carotid artery using an end-to-side technique. B) Self-made drug-perfusion device.

Mentions: New Zealand albino rabbits weighing 2.6 ± 0.3 kg were obtained from the Laboratory Animal Center of Shandong University. Animals received humane care, and the experiments were performed in accordance with the guidelines of the Animal Care and Use Committee of Shandong University. After intramuscular injection of ketamine 2 mg/kg, stable anesthesia was maintained by continuous infusion of pentobarbital administered through the ear vein at a rate of 200 μg/kg/min. The external jugular vein and common carotid artery on the same side were isolated (about 4 cm in length). Heparin sodium 125 U/kg was injected intravenously after the vessels were freed, and a segment of vein about 3 cm in length was resected. The common carotid artery was clamped proximally and distally to the planned anastomosis with two bulldog clips. Both ends of the prepared external jugular vein were anastomosed end-to-side into the common carotid artery with 7–0 Prolene. Once the anastomosis was completed, the original common carotid artery between the two anastomotic ends (about 3 cm in length) was ligated and resected. The bulldog clips were removed, and the vein graft filled with arterial blood immediately (Figure 1A). Intravenous penicillin G procaine (0.5 million units) was administered during surgery and daily for three days postoperatively. The rabbits were fed aspirin 2 mg/kg/day for anticoagulation from the second postoperative day until the end of the study. All the operations were performed by the same two surgeons.


Pretreatment with intraluminal rapamycin nanoparticle perfusion inhibits neointimal hyperplasia in a rabbit vein graft model.

Liu K, Cao G, Zhang X, Liu R, Zou W, Wu S - Int J Nanomedicine (2010)

A) Rabbit model of interposition of external jugular vein into the common carotid artery using an end-to-side technique. B) Self-made drug-perfusion device.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2963931&req=5

f1-ijn-5-853: A) Rabbit model of interposition of external jugular vein into the common carotid artery using an end-to-side technique. B) Self-made drug-perfusion device.
Mentions: New Zealand albino rabbits weighing 2.6 ± 0.3 kg were obtained from the Laboratory Animal Center of Shandong University. Animals received humane care, and the experiments were performed in accordance with the guidelines of the Animal Care and Use Committee of Shandong University. After intramuscular injection of ketamine 2 mg/kg, stable anesthesia was maintained by continuous infusion of pentobarbital administered through the ear vein at a rate of 200 μg/kg/min. The external jugular vein and common carotid artery on the same side were isolated (about 4 cm in length). Heparin sodium 125 U/kg was injected intravenously after the vessels were freed, and a segment of vein about 3 cm in length was resected. The common carotid artery was clamped proximally and distally to the planned anastomosis with two bulldog clips. Both ends of the prepared external jugular vein were anastomosed end-to-side into the common carotid artery with 7–0 Prolene. Once the anastomosis was completed, the original common carotid artery between the two anastomotic ends (about 3 cm in length) was ligated and resected. The bulldog clips were removed, and the vein graft filled with arterial blood immediately (Figure 1A). Intravenous penicillin G procaine (0.5 million units) was administered during surgery and daily for three days postoperatively. The rabbits were fed aspirin 2 mg/kg/day for anticoagulation from the second postoperative day until the end of the study. All the operations were performed by the same two surgeons.

Bottom Line: On postoperative day 28, the grafts and normal veins were harvested for histologic examination, flow cytometry analysis, and high-performance liquid chromatography measurement.Compared with Group 1, the intima of the grafts were thickened, the ratio of intimal area to vessel area increased, and the collagen volume index of the vein grafts increased significantly in Groups 2 and 3.The cell proliferation index in Group 1 (21.11 ± 3.15%) was much lower than that in Group 2 (30.35 ± 2.69%) and in Group 3 (33.86 ± 8.72%).

View Article: PubMed Central - PubMed

Affiliation: Department of Cardiovascular Surgery, Qilu Hospital of Shandong University, Jinan, People’s Republic of China.

ABSTRACT

Purpose: Poly lactic-co-glycolic acid nanoparticles (PLGA-NP) are widely used as a biodegradable biomaterial in medicine. Rapamycin-eluting stents have been used for prevention of restenosis during surgery. This study investigated the effect of pretreatment with intraluminal perfusion of carbopol-encapsulated rapamycin-loaded PLGA nanoparticles (RAP-PLGA-NP) on neointimal hyperplasia in a rabbit vein graft model.

Methods: A segment of common carotid artery was replaced with a segment of external jugular vein in 60 rabbits which were then separated into four treatment groups, ie, Group 1, in which vein grafts were pretreated with intraluminal RAP-PLGA-NP perfusion, Group 2 in which vein grafts underwent equivalent empty vehicle (PLGA-NP) perfusion, Group 3, in which vein grafts received no treatment, and Group 4, which served as a sham operation group receiving normal vein contrast. On postoperative day 28, the grafts and normal veins were harvested for histologic examination, flow cytometry analysis, and high-performance liquid chromatography measurement.

Results: Compared with Group 1, the intima of the grafts were thickened, the ratio of intimal area to vessel area increased, and the collagen volume index of the vein grafts increased significantly in Groups 2 and 3. The cell proliferation index in Group 1 (21.11 ± 3.15%) was much lower than that in Group 2 (30.35 ± 2.69%) and in Group 3 (33.86 ± 8.72%). By high-performance liquid chromatography measurement, retention of rapamycin was detected in Group 1 (11.2 ± 0.37 μg/10 mg) 28 days after single drug perfusion.

Conclusion: Pretreatment with intraluminal RAP-PLGA-NP perfusion may inhibit neointimal hyperplasia in vein grafts by penetrating into local tissue and limiting cell proliferation.

Show MeSH
Related in: MedlinePlus