J Korean Neurosurg Soc.  2021 Sep;64(5):693-704. 10.3340/jkns.2020.0303.

The Protective Effects of Statins Towards Vessel Wall Injury Caused by a Stent Retrieving Mechanical Thrombectomy Device : A Histological Analysis of the Rabbit Carotid Artery Model

• Lee SH
• Shin HS
• Oh I

• KMID: 2519696
• DOI: http://doi.org/10.3340/jkns.2020.0303

Abstract

Objective
: Endovascular mechanical thrombectomy (MT) has been regarded as one of the standard treatments for acute ischemic stroke caused by large vessel occlusion. Despite the wide use of stent retrievers for MT, arterial intimal damage caused when deployed stent is pulled has been a certain disadvantage. We hypothesized that statin could protect and stabilize vessel damage after endovascular MT using a stent retriever. In this animal study, we observed the protective effects of the statins towards MT-induced vessel wall injury.
Methods
: Twenty-eight carotid arteries of fourteen rabbits were used in the experiments with MT using stent retriever. We divided the rabbits into four groups as follows : group 1, negative control; group 2, positive control; group 3, statin before MT; and group 4, statin after MT. After MT procedures, we harvested the carotid arteries and performed histomorphological and immunohistochemical analyses.
Results
: In histomorphological analysis with hematoxylin and eosin and Masson’s trichrome stain, significant intimal thickening (p<0.05) was observed in the positive control (group 2), compared to in the negative control (group 1). Intimal thickening was improved in the statin-administered groups (groups 3 and 4 vs. group 2, p<0.05). We also observed that statin administration after MT (group 4) resulted in a more effective decrease in intimal thickness than statin administration before MT (group 3) (p<0.05). We performed immunohistochemical analysis with the antibodies for tumor necrosis factor-alpha (TNF-α), cluster of differentiation (CD)11b, and CD163. In contrast to the negative control (group 1), the stained percentage areas of all immunological markers were markedly increased in the positive control (group 2) (p<0.05). Based on statin administration, the percentage area of TNF-α staining was significantly reduced (p<0.05) in group 3, compared to the positive control group (group 2). However, significant differences were not observed for CD11b and CD163 staining. In group 4, no significant differences were observed for TNF-α, CD11b, and CD163 staining (p≥0.05). The differences in the percentage areas of the different markers between the statin-administered groups (groups 3 and 4) were also not revealed.
Conclusion
: We presented that statin administration before and after MT exerted protective effects towards vessel wall injury. The efficacy of statins was greater post-administration than pre-administration. Thus, statin administration in routine prescriptions in the peri-procedural period is strongly advised.

Keyword

Thrombectomy; Stents; Hydroxymethylglutaryl-CoA reductase inhibitors; Rabbits

Figure

• 

  Fig. 1. Exposure of the rabbit right femoral artery. After shaving the groin area of the rabbit (A), we made a skin incision (length, 2 cm) (b). The right femoral artery was exposed by carefully dissecting the muscle and fascia layers (c).

• 

  Fig. 2. Procedure for endovascular MT using stent retrievers in the rabbit. The microcatheter was navigated via the right femoral artery to the distal carotid artery through a 4 F sheath (A). A stent retriever was introduced into the microcatheter and deployed in the carotid artery (b). For tight apposition of the stent to the vessel wall, we used the ‘push and fluff technique’ while deploying the stent (c). After 2–3 minutes, the deployed stent was pulled back to the proximal segment of the carotid artery (d).

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  Fig. 3. Microscopic view of the H&E and Masson’s trichrome stained tissues. The tunica intima of the negative control group (group 1) shows a single thin layer of endothelial cells. Marked thickening of tunica intima can be observed in the positive control group (group 2). In the statin-administered groups 3 and 4, a significant decrease in intimal thickening can be observed (magnification ×20 on 1st column, magnification ×200 on 2nd and 3rd columns). H&E : hematoxylin and eosin, G1 : group 1, G2 : group 2, G3 : group 3, G4 : group 4.

• 

  Fig. 4. Histomorphological analysis of the intimal thickness in the hematoxylin and eosin (H&E) and Masson’s trichrome stained tissues. Marked intimal thickening was observed in the groups for which endovascular mechanical thrombectomy was performed. compared to the positive control group (group 2), the statin-administered groups (groups 3 and 4) showed decreased intimal thickness. The statistical analysis was performed using one-way analysis of variance (ANOVA) for three or more groups. Post-hoc was performed using duncan’s method. *p<0.05 vs. the positive control group. †p<0.05 between the statin-administered groups (before and after endovascular mechanical thrombectomy).

• 

  Fig. 5. Microscopic view of the immunohistochemically stained tissues. The stained percentage areas were markedly increased in the positive control group (group 2), compared to in the negative control group (group 1). Statin administration reduced the observed percentage areas of all immunological antibodies (magnification ×200 for all samples). TNF-α : tumor necrosis factor-α, cd : cluster of differentiation, G1 : group 1, G2 : group 2, G3 : group 3, G4 : group 4.

• 

  Fig. 6. Immunohistochemical analysis of the inflammatory markers. The percentage area of all immunological antibodies significantly increased in positive control group (group 2), compared to in the negative control group (group 1). In group 3, the percentage area of TNF-α staining was significantly reduced (p<0.05), compared to the positive control group (group 2), but significant differences were not observed for cd11b and cd163 staining. In group 4, no significant differences were observed for TNF-α, cd11b, and cd163 staining (p≥0.05). The statistical analysis was performed using one-way analysis of variance (ANOVA) for three or more groups. *p<0.05 vs. positive control group. TNF-α : tumor necrosis factor-α, cd : cluster of differentiation.

Reference

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