Endovascular procedures cause transient endothelial injury but do not disrupt mature neointima in Drug Eluting Stents

Abstract

Extensive application of coronary intravascular procedures has led to the increased need of understanding the injury inflicted to the coronary arterial wall. We aimed to investigate acute and prolonged coronary endothelial injury as a result of guidewire use, repeated intravascular imaging and stenting. These interventions were performed in swine (N = 37) and injury was assessed per coronary segment (n = 81) using an Evans Blue dye-exclusion-test. Scanning electron microscopy and light microscopy were then used to visualize the extent and nature of acute (<4 hours) and prolonged (5 days) endothelial injury. Guidewire and imaging injury was mainly associated with denudation and returned to control levels at 5 days. IVUS and OCT combined (Evans Blue staining 28 ± 16%) did not lead to more acute injury than IVUS alone (33 ± 15%). Stent placement caused most injury (85 ± 4%) and despite early stent re-endothelialization at 5 days, the endothelium proved highly permeable (97 ± 4% at 5 days; p < 0.001 vs acute). Imaging of in-stent neointima at 28 days after stent placement did not lead to neointimal rupture. Guidewire, IVUS and OCT induce acute endothelial cell damage, which does not increase during repeated imaging, and heals within 5 days. Interestingly, endothelial permeability increases 5 days post stenting despite near complete re-endothelialization.

Figure 1

Flow chart study groups. The flow chart displays the number of studied segments per intervention for the acute injury group in native arteries and the prolonged injury group in native arteries. It also displays the stented segments used to study acute neointimal injury caused by OCT-imaging 28 days post stenting and the control segments 28 days post stenting in which no OCT-imaging was performed. IVUS = Intravascular ultrasound; OCT = optical coherence tomography. DES = Drug eluting stent.

Figure 2

Evans Blue Vascular Damage. Challenging the vasculature with Evans Blue (EB) following vascular imaging reveals areas of endothelial cell permeability or denudation by staining the arterial wall blue. Underneath a functional endothelium, the arterial wall remains unstained (A,B). Scanning electron microscopy (C,D) shows that permeability is mainly caused by overt denudation (i.e. endothelial cell loss), resulting in penetration of the blue dye. The line delineates the area stained blue in B. D shows islands of intact endothelial cells (EC).

Figure 3

Vessel wall injury. Scanning electron microscopy overviews, details in relation to the Evans Blue dye-exclusion test (right) showing vascular injury by means of different imaging catheters. Images show that vascular imaging as well as engaging an artery with a guidewire induce vascular injury. (A) Guidewire; (B) IVUS imaging; (C) IVUS + OCT imaging, (D) control artery without injury. IVUS = Intravascular ultrasound; OCT = optical coherence tomography.

Figure 4

Vessel wall injury after stenting. Evans Blue Dye-exclusion acute (A) and at 5 days following stent implantation (B). The non-stented adjacent segments clearly indicate areas of damage inflicted by the guidewire and the stent delivery system during stent placement. At 5 days, the injury inflicted by the guidewire and delivery system has been repaired (*) while stent induced permeability is still present both between and over the stent struts, despite a near complete endothelial stent strut coverage (C,D).

Figure 5

Histology after stenting. Microscopy of control (A) and imaged (B) stent segment showing acute oedema (arrows) as a result of imaging induced denudation. Haematoxylin Eosin stain.

Figure 6

Denudated segments. Microscopy of denuded segments showing microthrombi (A, arrow) and leukocyte adhesion (B, arrow). Haematoxylin Eosin stain.