Vascular response to coronary artery stenting in mature and juvenile swine

Sheehy, Alexander; Hsu, Steve; Sinn, Irene; Tai, Julie; Kolodgie, Frank D.; Nakazawa, Gaku; Yazdani, Saami K.; Quee, Shawn Chin; Virmani, Renu; Polyakov, Igor

doi:10.1016/j.carrev.2011.05.003

Cited by 8 publications

(4 citation statements)

References 37 publications

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“…The initial fluid WSS poststenting initiates the signal transduction for tissue remodeling. Studies by Sheehy et al (40) and Cejna et al (7) found that the reendothelization process takes 4 -8 wk, beyond the time frame of the present study (4 wk). Therefore, the effect of the fluid forces persists.…”

Section: Discussionmentioning

confidence: 79%

“…Specifically, it has been observed clinically that the sites of neointimal hyperplasia (IH) highly correlate with sites of low WSS (33). Furthermore, nonuniform WSS spatial distribution [higher WSS gradient (WSSG)] and a higher oscillatory shear index (OSI) were also found to contribute to cell migration and differentiation (40,46). After stent deployment, the struts compress the vessel wall and cause flow disturbance at the intima acutely.…”

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confidence: 96%

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Mis-sizing of stent promotes intimal hyperplasia: impact of endothelial shear and intramural stress

Chen

Sinha

Choy

et al. 2011

American Journal of Physiology-Heart and Circulatory Physiology

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Stent can cause flow disturbances on the endothelium and compliance mismatch and increased stress on the vessel wall. These effects can cause low wall shear stress (WSS), high wall shear stress gradient (WSSG), oscillatory shear index (OSI), and circumferential wall stress (CWS), which may promote neointimal hyperplasia (IH). The hypothesis is that stent-induced abnormal fluid and solid mechanics contribute to IH. To vary the range of WSS, WSSG, OSI, and CWS, we intentionally mismatched the size of stents to that of the vessel lumen. Stents were implanted in coronary arteries of 10 swine. Intravascular ultrasound (IVUS) was used to size the coronary arteries and stents. After 4 wk of stent implantation, IVUS was performed again to determine the extent of IH. In conjunction, computational models of actual stents, the artery, and non-Newtonian blood were created in a computer simulation to yield the distribution of WSS, WSSG, OSI, and CWS in the stented vessel wall. An inverse relation (R(2) = 0.59, P < 0.005) between WSS and IH was found based on a linear regression analysis. Linear relations between WSSG, OSI, and IH were observed (R(2) = 0.48 and 0.50, respectively, P < 0.005). A linear relation (R(2) = 0.58, P < 0.005) between CWS and IH was also found. More statistically significant linear relations between the ratio of CWS to WSS (CWS/WSS), the products CWS × WSSG and CWS × OSI, and IH were observed (R(2) = 0.67, 0.54, and 0.56, respectively, P < 0.005), suggesting that both fluid and solid mechanics influence the extent of IH. Stents create endothelial flow disturbances and intramural wall stress concentrations, which correlate with the extent of IH formation, and these effects were exaggerated with mismatch of stent/vessel size. These findings reveal the importance of reliable vessel and stent sizing to improve the mechanics on the vessel wall and minimize IH.

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Section: Discussionmentioning

confidence: 79%

mentioning

confidence: 96%

Mis-sizing of stent promotes intimal hyperplasia: impact of endothelial shear and intramural stress

Chen

Sinha

Choy

et al. 2011

American Journal of Physiology-Heart and Circulatory Physiology

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“…Age has been shown to have a significant impact on the posttraumatic response after different types of injuries. Sheehy et al (77) were able to show that juvenile pigs demonstrated a significantly different immunological response compared with older animals. Furthermore, TBI resulted in an increased cerebral blood flow in young animals, whereas it was decreased in older pigs (78).…”

Section: Limitations Of Existing Trauma Modelsmentioning

confidence: 99%

Combined Hemorrhage/Trauma Models in Pigs - Current State and Future Perspectives

Hildebrand¹,

Andruszkow²,

Huber‐Lang³

et al. 2013

Shock

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“…Low inflammation and endothelialization have been reported following everolimus-eluting stent implantation in healthy rabbits [28] and swine [29,30] as well as in atherosclerotic rabbits [31]. Other investigators have described the vessel healing response to everolimus-eluting stents in overlap configurations as well [32].…”

Section: Discussionmentioning

confidence: 99%

Comparative vascular responses three months after paclitaxel and everolimus-eluting stent implantation in streptozotocin-induced diabetic porcine coronary arteries

Sheehy

Hsu

Bouchard

et al. 2012

Cardiovasc Diabetol

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BackgroundDiabetes remains a significant risk factor for restenosis/thrombosis following stenting. Although vascular healing responses following drug-eluting stent (DES) treatment have been characterized previously in healthy animals, comparative assessments of different DES in a large animal model with isolated features of diabetes remains limited. We aimed to comparatively assess the vascular response to paclitaxel-eluting (PES) and everolimus-eluting (EES) stents in a porcine coronary model of streptozotocin (STZ)-induced type I diabetes.MethodTwelve Yucatan swine were induced hyperglycemic with a single STZ dose intravenously to ablate pancreatic β-cells. After two months, each animal received one XIENCE V® (EES) and one Taxus Liberte (PES) stent, respectively, in each coronary artery. After three months, vascular healing was assessed by angiography and histomorphometry. Comparative in vitro effects of everolimus and paclitaxel (10-5 M–10-12 M) after 24 hours on carotid endothelial (EC) and smooth muscle (SMC) cell viability under hyperglycemic (42 mM) conditions were assayed by ELISA. Caspase-3 fluorescent assay was used to quantify caspase-3 activity of EC treated with everolimus or paclitaxel (10-5 M, 10-7 M) for 24 hours.ResultsAfter 3 months, EES reduced neointimal area (1.60 ± 0.41 mm, p < 0.001) with trends toward reduced % diameter stenosis (11.2 ± 9.8%, p = 0.12) and angiographic late-loss (0.28 ± 0.30 mm, p = 0.058) compared to PES (neointimal area: 2.74 ± 0.58 mm, % diameter stenosis: 19.3 ± 14.7%, late loss: 0.55 ± 0.53 mm). Histopathology revealed increased inflammation scores (0.54 ± 0.21 vs. 0.08 ± 0.05), greater medial necrosis grade (0.52 ± 0.26 vs. 0.0 ± 0.0), and persistently elevated fibrin scores (1.60 ± 0.60 vs. 0.63 ± 0.41) with PES compared to EES (p < 0.05). In vitro, paclitaxel significantly increased (p < 0.05) EC/SMC apoptosis/necrosis at high concentrations (≥10-7 M), while everolimus did not affect EC/SMC apoptosis/necrosis within the dose range tested. In ECs, paclitaxel (10-5 M) significantly increased caspase-3 activity (p < 0.05) while everolimus had no effect.ConclusionAfter 3 months, both DES exhibited signs of delayed healing in a STZ-induced diabetic swine model. PES exhibited greater neointimal area, increased inflammation, greater medial necrosis, and persistent fibrin compared to EES. Differential effects of everolimus and paclitaxel on vascular cell viability may potentially be a factor in regulating delayed healing observed with PES. Further investigation of molecular mechanisms may aid future development of stent-based therapies in treating coronary artery disease in diabetic patients.

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Vascular response to coronary artery stenting in mature and juvenile swine

Cited by 8 publications

References 37 publications

Mis-sizing of stent promotes intimal hyperplasia: impact of endothelial shear and intramural stress

Mis-sizing of stent promotes intimal hyperplasia: impact of endothelial shear and intramural stress

Combined Hemorrhage/Trauma Models in Pigs - Current State and Future Perspectives

Comparative vascular responses three months after paclitaxel and everolimus-eluting stent implantation in streptozotocin-induced diabetic porcine coronary arteries

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