Research Of Chinese Medicine In Preventing Vascular Injury After Percutaneous Coronary Intervention

Drug eluting stents (DES) dramaticlly address the issues of vascular smooth muscle cells proliferation and in-stent restenosis (ISR), however, at the cost of the increased risk of stent thrombosis (ST), which compromises the clinical outcome of PCI. Recently, clinical research demonstrate that patients with coronary artery disease after PCI receiving Chinese medicine combining with conventional treatment alleviate clinical syndromes and improve quality of life for patients with PCI, further reducing the frequency of angina, improving cardiac function and declining the rate of ISR. But, as to the clinical effects for patients post-PCI receiving Chinese medicine via sydrome differentiation in Traditional Chinese Medicine (TCM), reflecting the uniformity of principles and prescriptions of TCM, combining with the conventional treatment, it remains unclear。In order to detect the clinical outcomes of Chinese herbs through sydrome differentiation in TCM with conventional treatment for paitents with ACS after PCI, we performed a clinical research of 203 paitents enrolled.In addition, biomedical materials applied to DES present many issues, such as aforementioned ISR and ST, and local inflammation, which decline the long-term outcomes for patients post PCI. Even though investigating the third-generation DES, the clinical endpoint events of 1 year follow-up are still not improved. Previous research demonstrated that sesquiterpenoids compounds of E’zhu play a role in impeding vascular smooth muscle cells and reducing endothelial cells injury. In this context, with nanoporous technology, the effects of E’zhu coating stents on promoting endothelial healing, and preventing ISR and ST were observe via Chinese minipigs which the coronary arteries are similar to humen beings. This paper divided three parts:Part I ReviewsReview 1 Advances in drug eluting stentsAdvent of drug eluting stents (DES) dramatically reduces the rate of in-stent restenosis (ISR). But, because of the relatively high fatality, stent thrombosis (ST) eliciting by DES affects the clinical effects. Recently, tremendous research has been demonstrated that thrombosis formation is related to multiple factors, including delay of endothelial healing, struts malapposition, local hypersensitivity and neoatherosclerosis. New generation DES, such as biodegradable stents, are detected to relieve the pathological changes of stented vessles after PCI in order to increase the clinical outcomes.Review 2 Advances in Studies of curcuma zedoary extracts on Inhibiting of Coronary Artery Restenosis after PCICurcuma zedoary (E’Zhu), a traditional herb, mainly consists of essential oil and curcuminoid, capable of inhibiting platelet aggregation, lowing cholesterol, anti-oxidants, and anti-inflammation. Recently, certain extracts and components of E’ZHU have positive effects on vascular wall, including protecting against vascular endothelial dysfunction via enhancing heme oxygenase-1 activity, suppressing infiltration of inflammatory cells through inhibiting NF-κB, tumor necrosis factor receptor-6 (TRAF-6) and vascular cell adhesion molecule-1 (VCAM-1), and hampering vascular smooth muscle cells (SMCs) proliferation and migration by inhibition of oxidation of cellular phosphatases. Recently, a certain extracts of E’Zhu have been focused on the studies of drug-eluting stent, being playing a meaningful role in preventing in-stent restenosis and thrombosis formation after percutaneous coronary intervention, and potentially representing a promising drug in preserving against endothelial cells injury due to stent implanting.Part II Randomized controlled trial of individualized Chinese medicine regimen on patients with acute coronary syndrome after PCIObjective:Combining with western routine therapy, evaluating the clinical effects of patients with ACS after PCI treated with tailored regimen of Traditional Chinese Medicine (TCM) based on the sydrome differentiation.Methods:203 patients were enrolled in this randomized, controlled clinical trial. According to dialectical of TCM, patients recruited were assigned to Intermingled Phlegm and Blood-Stasis (IPBS), Syndrome of Blockade of Heart Vessel (SBHV) or Qi-Deficiency with Blood-Stasis (QDBS). Treatment group received Danlou pills, Guanxin salvia dripping pills or QishenYiQi dripping pills adding to western routine medication. And the control group administrated western routine medication. At the end of 6 months and 12 months of treatment, primary endpoint events (including cardiac death, repeat revascularization, and nonfatal recurrent myocardial infarction), and secondary endpoint events, composited of rehospitalization for coronary artery disease congestive heart failure, nonfatal cerebrovascular diseases, malignant arrhythmias and other thrombotic events, were detected. TCM syndrome score, blood-stasis syndrome score, blood lipid levels, cardiac function and Seattle angina questionnaire (SAQ) score were measured. And security index were assessed.Results:(1) Based on the study standard,203 patients were included and 203 were finished the fellow-up, which the treatment group was 107 and the control 96. Follow-up for 1 year, the rate of primary endpoints (cardiac death, repeat revascularization, and nonfatal recurrent myocardial infarction) was 1.86%, and the rate of secondary endpoints (rehospitalization for acute coronary syndrome, congestive heart failure, nonfatal cerebrovascular diseases, malignant arrhythmias and other thrombotic events) 3.73% in the treatment group. The rate of primary endpoints was 4.16%, and the rate of secondary endpoints 11.45% in the control group. Although there was no significant difference in primary endpoint between groups (P=0.332), the rate of secondary endpoints was significant lower in the treatment group compared with the control group (P=0.036).(2) Comparing TCM syndrome score. Despite the treatment group of IPBS showed a tendency of reducing TCM syndrome score at the end of 6 months, but didn’t reach statistical difference compared to the control group (P=0.540); at the end of 12 months, the TCM syndrome score was less in the treatment group of IPBS than in the control group (P=0.034). The TCM syndrome score was lower in the treatment group of SBHV at the end of 6 months compared to the control group (P=0.014), but, without difference at the end of 12 months (P=0.405). The treatment group of QDBS didn’t reach significance in declining the TCM syndrome score compared to the control group at the end of 6 months (P=0.095), but was much reduced at the end of 12 months with its counterpart (P=0.027).(3) Comparing blood-stasis syndrome score:Despite less blood-stasis syndrome score, the treatment group of IPBS was not different with its counterpart during the follow-up (P=0.379, P=0.059, respectively). The treatment group of SBHV was superior to the control group (P>0.05) in lowering the blood-stasis syndrome score (P=0.029, P=0.019, respectively) during follow-up period. The treatment group of QDBS also was remarkable to decline the blood-stasis syndrome score compared to the control group (P=0.002, P<0.001, respectively)(4) Comparing the blood lipid level:The triglyceride level (TG) was lower in the treatment group of IPBS than in the control group at the end of 6 months (P=0.047), but was similar to the control group at the end of 12 months (P=0.545); the treatment group of IPBS was not different in reducing the total cholesterol level (TC) at the end of 6 months (P=0.061), but reached the significance at the end of 12 months (P=0.039). There was no significant difference in serum lipid level between the treatment group of SBHV and its counterpart (both P>0.05). The treatment group of QDBS had a lower level of TC compared to the control group (P=0.025) at the end of 6 months, without difference at the end of 12 months (P>0.05); The treatment group of QDBS was superior to increasing the level of HDL-C at the end of 12 months compared to the control one (P=0.002).(5) Comparing the cardiac function:The rate of cardiac wall motion abnormality was less in the treatment group compared to the control group at the end of 6 months (P=0.032), but was no difference at the end of 12 months (P>0.273). At the end of 6 months, the rate of valve disorders in the treatment group was no difference compared with the control group (P=0.586), but was much less at the end of 12 months (P=0.015).(6) Comparing of Seattle angina questionnaire score:At the end of 6 months, the treatment group was superior to the control group in declining the angina frequency (P=0.034), although without difference at the end of 12 months (P=0.087). And the rest aspects of Seattle angina questionnaire score were no significance between groups (P>0.05).(7) Comparison of security index:At the end of 6 months, the percentage of sinus rhythm in the treatment group was similar compared with the control group (P>0.05), but was superior at the end of 12 months (P=0.019). At the end of 6 months and 12 months, the treatment of group was superior to the control group in mediating systolic pressure (P=0.002, P=0.008, respectively), and was remarkable to maintaining diastolic pressure at the end of 6 months (P=0.02), with no difference at the end of 12 months (P>0.05). As to hepotrenal function, there was no difference in glutamate pyruvate transaminase (ALT), glutamic oxalacetic transaminase (AST)、 blood urea nitrogen (BUN) and serum creatinine (Cr) between groups (P>0.05) during the follow-up. And for blood coagulation indexes, prothrombin time (PT), activate partial thromboplastin time (APTT), fibrinogen (Fbg) and thrombin time (TT) were similar between groups (P>0.05).Conclusion:(1) Chinese regimen applied to western routine reduce the rate of secondary endpoints, composited of rehospitalization for acute coronary syndrome, congestive heart failure, nonfatal cerebrovascular diseases, malignant arrhythmias and other thrombotic events, during a follow-up of 1 year.(2) On the basic background of combination with western routine therapy, Chinese regimen dialectically is powerful to reduce TCM syndrome score, blood-stasis score and angina frequency, and mediate the lipid level and cardiac function.(3) There is no risk of hepatorenal function damage and hemorrhage for patients with acute coronary syndrome after PCI receiving Chinese medicine dialectically.Part Ⅲ Preclinical research of nanopores-based guaiane-type sesquiterpenoids compounds of zedoary stents promotes swine coronary artery endothelial healing.Aims:Understanding nanopores-based guaiane-tye sesquiterpenoids compounds of zedoary eluting stents promotes arterial endothelial healing and reduces neointimal hyperplasia post-stenting in order to prevent stent thrombosis and in-stent stenosis.Methods:Establishing coronary artery balloon injury model, nanopores-based guaiane-tye sesquiterpenoids compounds of zedoary eluting stents (ZES), sirolimus eluting stents (SES) or bare metal stents (BMS) were randomized implanted in left anterior desceding artery (LAD), left circumflex artery (LCX) and right coronary artery (RCA) of domestic juvenile swine coronary arteries. Before and at 7d、14d and 28d, those stenting coronary arteries were examined by consistent coronary angiogram and optical coherence tomography, then, obtained to evaluate by scanning electron microscopy(SEM) and histopathology. Re-endothelialization score, rate of uncovered struts, lumen diameter and area, inflammation score and minimal thrombosis score were measured.Results:At 7 days post-stenting, compared with SES and BMS, ZES showed largely endothelial coverage (2.00±0.00 vs.1.00±1.00; 2.00±0.00 vs.0.50±0.58; P=0.014, P<0.001, respectively), lower uncovered struts percentage (1.10±2.91 vs. 46.56±20.40%; 1.10±2.91vs.53.82±44.23%; P=0.002, P=0.003, respectively), and less inflammation reaction (1.2±0.42 vs.1.9±0.32; 1.2±0.42 vs.2.05±0.39; both P<0.001).There was no significance in stented lumen diameter, lumen area and minimal thrombosis among groups (all P>0.05). After 28 days, compared to SES, ZES had higher re-endothelial scores (2.83±0.41 vs.1.43±0.79, P=0.007), less uncovered struts percentage(2.50±3.75 vs.22.10±24.24%, P=0.022), longer lumen diameter (2.58±0.60 vs.l.87±0.28mm, P=0.022), less inflammation scores (1.67 ±0.62 vs.2.30±0.66, P=0.003), and lower minimal thrombosis scores (0.47±0.83 vs.1.01±0.46, P=0.039); lumen area was no significant compared to SES group (2.77±0.05 vs.2.43±0.48mm2, P=0.227). Compared to BMS, scores of lumen diameter and area were higher (P=0.007, P=0.012, respectively), inflammatory score was less (P＜0.001) in ZES group. There was no significance in re-endothelial score, uncovered struts percentage and minimal thrombosis score between ZES and BMS groups at 28 days (P=0.05, P=0.143, P=0.283, respectively).Conclusion:Nanoporous guaiane-type sesquiterpenoids compounds of zedoary stents present properties of promoting re-endothelialization, preventing in-stent restenosis and stent thrombosis.