Rapamycin-coated expanded polytetrafluoroethylene bypass grafts exhibit decreased anastomotic neointimal hyperplasia in a porcine model

Cagiannos, Catherine; Abul-Khoudoud, Omran; deRijk, Waldemar G.; Shell, Daniel H.; Jennings, Lisa K.; Tolley, Elizabeth A.; Handorf, Charles R.; Fabian, Timothy C.

doi:10.1016/j.jvs.2005.06.018

Cited by 49 publications

(37 citation statements)

References 36 publications

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“…Both the coagulation system and the inflammatory processes contribute to the development of this neointima, which is a proliferation of myofibroblasts with endothelial cell ingrowth. [3][4][5][6] The neointima is associated with organizing thrombus and tends to be most severe at the anastomotic sites. 7 Furthermore, these patients are uniformly cyanotic, and other growth factors such as vascular endothelial growth factor have increased expression in this patient group, potentially intensifying neointimal growth.…”

Section: Article P 293mentioning

confidence: 99%

Aspirin

Tweddell

2007

Circulation

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ependence on an expanded polytetrafluoroethylene graft for provision of pulmonary blood flow is a common yet precarious interval through which a population of patients with congenital heart disease must pass. The goals of the systemic-to-pulmonary artery shunt are to relieve cyanosis and to provide time before establishing in-series circulation by either complete repair of 2-ventricle lesions or, in the case of the single-ventricle patient, a bidirectional Glenn shunt. In the case of patients with single-ventricle anatomy, this period of parallel circulation is necessary to permit the lung maturation and the reduction in pulmonary vascular resistance that are necessary for subsequent palliation. For patients who will ultimately achieve a 2-ventricle repair, the goals of a preliminary shunt may include increasing the size of the pulmonary artery size or having a larger, older patient at the time of repair. This period of parallel circulation is tenuous, and the patient remains at increased risk during this period of altered circulation. Article p 293With parallel circulation, cardiac output from the heart is partitioned to the lungs and body based on the relative resistances of the pulmonary and systemic circulations. If the shunt is large, the patient will experience excessive pulmonary blood flow and congestive heart failure. Furthermore, with a large shunt, diastolic pressure is low and coronary circulation may be impaired. With stress, autonomic reflexes will result in an acute increase in sympathetic tone. The elevation of systemic vascular resistance leads to acute increase in the ratio of pulmonary to systemic flow. In the face of limited cardiac output, this acute increase in the ratio of pulmonary to systemic flow can result in a critical reduction in systemic oxygen delivery. Therefore, autonomic reflexes aimed at maintaining vital organ perfusion with in-series circulation have an adverse effect in patients with parallel circulation and can result in a critical reduction in oxygen delivery. This is likely to be one mechanism of death for patients with parallel circulation. 1,2 Alternatively, if the shunt is sufficiently limiting, then increasing pulmonary blood flow in response to increased metabolic demands such as may occur with fever or exercise will not be possible, increased cyanosis results, and again a critical reduction in oxygen delivery will occur. Additional limitations of parallel circulation include the potential for parenchymal lung disease, anemia, and decreased cardiac output to result in worsening cyanosis. Decreased cardiac output from the single ventricle may be the result of myocardial dysfunction, atrioventricular valve regurgitation, or arrhythmias. In addition, dehydration will result in decreased preload with decreased cardiac output and may occur in the course of an acute illness resulting from decreased fluid intake, gastrointestinal loss, and/or fever. Diuretic use is common in this patient population and will limit the ability of the patient to autoregulate fluid status in t...

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Section: Article P 293mentioning

confidence: 99%

Aspirin

Tweddell

2007

Circulation

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“…[1][2][3] This fraction is expected to grow as both the incidence of repeat interventions and mean life spans of people increase. 4,5 Unfortunately, no current synthetic small-diameter grafts are suitable for CABG because they fail with high frequency due to thrombosis and intimal hyperplasia-both of which give rise to resistance to blood flow.…”

Section: Introductionmentioning

confidence: 99%

“…(3), where Q is the average rate of fluid flow and R is the average resistance between sampled points of pressure upstream (P purging ) and downstream (atmospheric pressure, P atm ) of a lumenal occlusion. (3) Grafts were loaded with fluid and allowed to cure for set times. The cured graft contents were then compressed at a constant rate until the graft contents were purged.…”

Section: Introductionmentioning

confidence: 99%

Coagulation-induced resistance to fluid flow in small-diameter vascular grafts and graft mimics measured by purging pressure

Nichols

Choudhary

Kodali

et al. 2013

J. Biomed. Mater. Res.

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In this study, the coagulation-induced resistance to flow in small-diameter nonpermeable Tygon tubes and permeable expanded polytetrafluoroethylene (ePTFE) vascular grafts was characterized by measuring the upstream pressure needed to purge the coagulum from the tube lumen. This purging pressure was monitored using a closed system that compressed the contents of the tubes at a constant rate. The pressure system was validated using a glycerin series with well-defined viscosities and precisely controlled reductions in cross-sectional area available for flow. This system was then used to systematically probe the upstream pressure buildup as fibrin glue, platelet-rich plasma (PRP) or whole blood coagulated in small-diameter Tygon tubing and or ePTFE grafts. The maximum purging pressures rose with increased clot maturity for fibrin glue, PRP, and whole blood in both Tygon and ePTFE tubes. Although the rapidly coagulating fibrin glue in nonpermeable Tygon tubing yielded highly consistent purging curves, the significantly longer and more variable clotting times of PRP and whole blood, and the porosity of ePTFE grafts, significantly diminished the consistency of the purging curves.

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“…Previous studies have indicated that the efficacy of rapamycin in stents might not persist for a long time period. 31,32 It has been suggested that even though retention of the drug could be detected at day 90, intimal proliferation could not be inhibited any further at this time point. 32 Therefore, the duration of effect of rapamycin in local tissue in vivo after ex vivo treatment needs further investigation.…”

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confidence: 99%

“…Moreover, no thrombosis or aneurysm occurred following treatment with RAP-PLGA-NP, which was in accordance with other studies. [18][19][20]31 The early thrombus occurring in some of the animals in our study might have been caused by manipulation rather than being an adverse effect of the drug. Previous studies have indicated that the efficacy of rapamycin in stents might not persist for a long time period.…”

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confidence: 99%

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

Cao²,

Zhang³

et al. 2010

IJN

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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 highperformance 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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Rapamycin-coated expanded polytetrafluoroethylene bypass grafts exhibit decreased anastomotic neointimal hyperplasia in a porcine model

Cited by 49 publications

References 36 publications

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Coagulation-induced resistance to fluid flow in small-diameter vascular grafts and graft mimics measured by purging pressure

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

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