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Experimental And Clinical Evaluation Of Vessel Remodeling And Endothelial Function After Drug-Eluting Stent Implantation

Posted on:2012-01-28Degree:DoctorType:Dissertation
Country:ChinaCandidate:F ZhangFull Text:PDF
GTID:1484303356468894Subject:Internal Medicine
Abstract/Summary:PDF Full Text Request
Part I:Experimental evaluation of coronary remodeling after drug-eluting stent implantationObjective:To evaluate the response of the coronary vessel wall to implantation of the bare metal stent (BMS), sirolimus-eluting stent (SES), and chitosan-heperin layer-by-layer self assembly (C/H LBL) coating stent by using serial intravascular ultrasound.Methods:The BMS, SES and C/H LBL stents were randomly implanted in the miniature pigs'coronary arteries. Serial intravascular ultrasound (IVUS) was performed immediately after the stent implantation and at 3-6 months follow-up. Quantitative IVUS analysis was then performed in the stent segments,5 mm coronary segments immediately proximal and distal to the stent.Results:Serial IVUS was available for 9 BMSs (BMS group),11 SESs (SES group), and 12 C/H LBL stents (LBL group). At follow-up, significantly larger lumen (SES group 6.34±0.89 mm2 vs. BMS group 4.31±1.28 mm2, P=0.001; LBL goup 5.43±0.88 mm2 vs. BMS group 4.31±1.28 mm2, P=0.029; respectively) and lower neointimal hyperplasia areas (SES group 0.28±0.35 mm2 vs. BMS group 2.69±1.58 mm2, P=0.002; LBL goup 1.40±0.96 mm2 vs. BMS group 2.69±1.58 mm2, P= 0.032; respectively) were seen in the SES group and LBL group compared with the BMS group (by ANOVA, P< 0.001). There was no significant difference between 3 groups in either the vessel area or the media& plaque behind stent area change (all P>0.05) from after the procedure to late follow-up. For both the proximal and the distal edges, the vessel and lumen areas were also comparable among 3 groups (all P>0.05). No late incomplete stent apposition was observed in all 3 groups.Conclusion:The marked reduction in neointimal hyperplasia with SES and C/H LBL stent is not associated with abnormal vascular response or edge effects at follow-up IVUS. Part II:Experimental evaluation of coronary endothelial function associated with drug-eluting stent, and chitosan-heperin layer-by-layer self assembly coating stentObjective:To evaluate the coronary endothelial function following percutatneous implantation of the bare metal stent (BMS), sirolimus-eluting stent (SES), and chitosan-heperin layer-by-layer self assembly (C/H LBL) coating stent at follow-up.Methods:The BMS, SES and C/H LBL stents were randomly implanted in the miniature pigs'coronary arteries. Endothelial function was estimated by incremental acetylcholine (Ach) (6,60,600 ug) and nitroglycerin (200 ug) infusions into the coronary ostium at 3-6 months follow-up. The vascular response was quantitatively measured in the 10-mm segments proximal and distal to the stent.Results:The coronary vasomotor response was tested for 12 BMSs (BMS group),13 SESs (SES group), and 16 C/H LBL stents (LBL group). In the SES group, more intense vasoconstriction to incremental doses of Ach was observed at follow-up compared with the BMS goup, and was more prominent in the distal segments (-14.1±6.2%,-23.5±13.7%,-52.8±22.5%, respecitively to incremental doses of Ach) than the proximal segments (-5.3±2.7%,-5.9±3.1%,-7.3±3.0%, respecitively to incremental doses of Ach). Endothelial function associated with the C/H LBL stent (distal:-3.2±2.1%,-3.8±1.9%,-4.4±2.9%; proximal:-2.8±2.2%,-4.9±1.9%,-5.2±2.1%, respecitively to incremental doses of Ach) and BMS (distal:-4.2±2.6%,-5.4±2.9%,-5.7±3.0%; proximal:-3.3±2.1%,-4.6±2.7%,-4.9±3.5%, respecitively to incremental doses of Ach) was preserved at follow-up compared with the SES. There is no significant difference in endothelium-dependent vasomothion between LBL group and BMS goup. Endothelium-independent vasodilation to nitrate did not differ significantly among the study groups.Conclusion:SES implantation may induce significant impairment of the endothelium-dependent vasomotor function in the adjacent portion of the stent segment, while the endothelial function associated with C/H LBL stent can be well preserved. Part III:Intravascular ultrasonic evaluation in patients with late incomplete stent apposition after drug-eluting stent implantationObjective:To evaluate the coronary morphological characteristics and present the clinical outcomes of a more than 2-year follow-up in patients with late incomplete stent apposition (ISA) after drug-eluting stent implantation.Methods:From the IVUS database of our institute,15 consecutive patients who underwent DES implantation into de novo lesions and had documented ISA at follow-up by IVUS were identified. The ISA group was compared with a matched control group of patients (n=30) who had no evidence of ISA at follow-up. Clinical follow-up was available up to 41 months after DES implantation and up to 33 months after identification of ISA.Results:Of the 15 documented late ISA after DES implantation, two located at the edge (within 5 mm from stent margin) while 13 in the body of the stent. The maximum area and arc of ISA measured 5.3±2.2 mm2 and 163±67°, respectively. In patients with late ISA, the maximum external elastic membrane (EEM) area of stent segment with ISA was significantly larger than the adjacent stent segment without ISA (24.1±3.3 vs.20.1±3.1 mm2, P= 0.002), while stent area, plaque plus media (P&M) area and intrastent lumen area were comparable (P>0.05). Compared to the matched control cohort without ISA at follow-up, the maximum EEM area was also significantly larger in the late ISA group (24.1±3.3 vs.18.8±4.2 mm2, P< 0.001), while the areas of reference EEM and lumen, stent, P&M behind the stent, intimal hyperplasia and intrastent lumen were all comparable between the two groups (P>0.05). Over a mean follow-up of(34±5) months (range 24-41 months),3 of the 15 patients (20.0%) suffered from ST elevated myocardial infarction with one death. Very late stent thrombosis in the area with late ISA was demonstrated by the emergency coronary angiography in all 3 patients.Conclusion:Late ISA revealed at follow-up after DES implantation was associated with significant positive vessel remodeling. With regard to the clinical sequelae, late ISA may be associated with a high incidence of very late stent thrombosis.
Keywords/Search Tags:vessel remodeling, drug-eluting stent, bare metal stent, chitosan-heperin layer-by-layer coating stent, endothelial function, vasomotor response, incomplete stent apposition, vessel remodeling, clinical follow-up
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