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Background and Objectives Pyrrole-Imidazole polyamide (PIP) is a novel gene silencer that can be readily designed and synthesised to target any gene. Contrary to traditional gene-silencing agents, PIP is resistant to nucleases and can enter into the nuclei of target cells without any particular delivery system. Moreover, PIP has a low molecular weight, a high efficiency of cellular uptake and bioavailability, and is hydrophobic and lipophilic, making it pharmacokinetically suitable for loading onto the metal stent. The present study was designed to evaluate the potential effects of PIP on in-stent restenosis and re-endothelialisation in rat abdominal aorta stenting models. Methods Rats were assigned to four groups (n=10 for each group): Control group, Bare-metal stent group, PIP-eluting stent group and Mismatch PIP-eluting stent group. In vitro pharmacological release kinetics was analysed by HPLC. The re-endothelialisation indices were determined by scanning electron microscopy (n=3). The expression of LOX-1, NADPH p22phox, NADPH p47phox will be determined by quantitative real-time PCR and Westernblot. The oxidative stress in the aorta will be determined by measuring aortic MDA levels. Sections in methylmethacrylate will be cut into 5-μm thickness and stained with hematoxylin-eosin. The area of neointimal hyperplasia (NIH), the rate of restenosis, and the injury and inflammation scores were measured. Results In vitro pharmacological release kinetics showed that PIP eluting stents showed almost complete release of the PIP with in 24h. In vivo pharmacological release kinetics demonstrated that trace amount of PIP was still remained in the local aorta tissues. Scanning electron microscopy showed that re-endothelialisation was nearly complete in all the three stents groups (n=3) at 14 days after stents implantation. The expression of LOX-1, NADPH p22phox, NADPH p47phox and the vascular MDA levels was significantly increased in BMS group compared with control group at 28 days after stents implantation (p 0.05). Conclusions PIP targeting LOX-1 eluting stents could decrease in-stent restenosis (ISR) without impairing re-endothelialisation by silencing LOX-1 and lowering oxidative stress. These results indicated that PIP targeting LOX-1 is considered to be a feasible gene silencing agent using the next generation of DES for the prevention of in-stent restenosis of the coronary artery.

Background and Objectives Myocardial ischemia-reperfusion injury (MIRI) can be alleviated by ischemia post-conditioning (IPC) and/or statin post-conditioning (SPC), and their combination. However, it is unclear how the cardio-protection works in impaired glucose tolerance (IGT) state since IGT significantly abolishes intrinsic myocardial self-protection, and if it does so, what mechanisms are involved in the process. This study aims to investigate the cardio-protective effects and possible mechanisms by combination of SPC and IPC in the IGT rats. Methods An IGT model was successfully created in 72 out of 117 male Wistar rats by injecting STZ, which were randomly allocated into six groups (n=12 per group): Sham group, treated with open chest operation but without myocardial ischemia as controls; I/R group, with ischemia 30 min and reperfusion 2 h in LAD territory but without other interventions; IPC group, treated with initial ischemia 30 min, then 3 consecutive runs of 10 s reperfusion/10s ischemia, and final reperfusion 2 h; SPC group, with initial ischemia 30 min, then pitavastatin (0.1 mg/kg) intravenously 3 min before reperfusion, and final reperfusion 2 h; ISPC group, with initial ischemia 30 min, then combination of three consecutive runs of 10 s reperfusion/10 s ischemia and pitavastatin 3 min before reperfusion, and final reperfusion 2 h; ISPC+LY294002 group, with initial ischemia 30 min, then combination of 3 consecutive runs of 10 s reperfusion/10 s ischemia, pitavastatin and PI3-K inhibitor LY294002 (0.3 mg/kg, intravenously) 3 and 15 mins before reperfusion, respectively. Results Compared with sham group, I/R group had larger infarct size (70.1±3.1% vs 0±0%, p Conclusions The combination of pitavastain and ischemic postconditioning enhances the cardioprotection against myocardial ischaemia-reperfusion injury in impaired glucose tolerance rats, and PI3K-Akt-eNOS may be a major signaling pathway mediated this cardioprotection.

Objectives Mesenchymal stem cells are sensitive to hypoxia under myocardial micro-environment of ischaemia and reperfusion. Ischemic postconditioning, which is cardioprotective against ischaemia-reperfusion injury, enhances in vivo survival and therapeutic effects of transplanted stem cells. In this study, we investigateded the effects of coronary effluent from postconditioned rat hearts on proliferation and survival of mesenchymal stem cells in vitro under hypoxia. Methods Isolated perfused rat hearts were subjected to 30 minutes of ischaemia and 60 minutes of reperfusion, and postconditioning was induced by 3 cycles of 30 sec reperfusion and 30 sec ischaemia before sustain edreperfusion. Inflammation-related factors in coronary effluent were assessed by ELISA. Mesenchymal stem cells from bone marrow of Sprague-Dawley rats were cultured with coronary effluentunder hypoxia (95% nitrogen and 5% carbon dioxide)for 18 hours. Cell proliferation was determined by methylthiazolyl tetrazolium. Survival was detected by Annexin V/PI. Results Compared with ischaemia-reperfusion group, postconditioning treatment increased the level of interleukin-10 and decreased the level of tumour necrosis factor-α, interleukin-1β in coronary effluent ( P P Conclusions We have demonstrated that coronary effluent from postconditioned hearts may promote the proliferation and survival of mesenchymal stem cells by suppressing inflammation under hypoxia.

Objectives group Methods group Results Compared with I/R group, different dosage (0.1, 0.5, 1.0 or 2.0 mg/kg) of atorvastatin intervention significantly decreased IS (p 0.05), cTnT (p>0.05), Flameng score (p>0.05) as well as myocardial expression of phosphorylated AKt (p>0.05), phosphorylated eNOS (p>0.05) and HSP70 (p>0.05) between groups. Conclusions Our data suggests that activation of the upstream PI3K-Akt-eNOS pathway and up regulation of the downstream protein HSP70 contribute to atorvastatin post conditioning cardio-protection in type 2 diabetic rat.

Background Both Transcatheter device closure (TCDC) or intraoperative device closure (IODC) have emerged as new minimally invasive alternatives to the classic surgery in the treatment of secundum atrial septal defect (ASD). However, the long-term safety and efficacy by the two methods for closuring large particularly huge ASD remains uncertain. Present study sought to investigate and compare the long-term clinical outcomes by using TC DC and IODC for closure of large-to-huge ASD. Methods A total 92 patients with large-to-huge ASD (a defect diameter of ≥30 mm), treated from January 2003 to Dec 2009, were included in this study. All the patients have been followed up until Dec 2010. The patients were assigned to either TCDC or IODC group according to the patients′ or their parents′ preference. Baseline physical exams, chest roentgenography, electrocardiography, and echocardiography were performed pre-procedure and at each follow-up visit. Results 42 patients underwent TCDC and 50 patients received IODC by using Amplatzer septal occluder (ASO). The average diameter of ASD was similar in the two groups (35.2±4.8 mm vs 34.9±4.4 mm, p>0.05). The immediate procedural success rate was 92.9% for TCDC and 98.0% for IODC (p=0.328). The peri-procedural complication rate was 9.5% for TCDC and 28.0% for IODC p Conclusions Present study confirmed the long-term safety and efficacy by using ASO for closure of large-to-huge ASD either by TCDC or IODC. However, the acute complication rate was lower and the length of hospital stay was shorter by TCDC.

Background High thrombus burden (HTB) is an independent predictor of no- or low-reflow during primary percutaneous coronary intervention (pPCI). This study sought to compare immediate versus delayed stenting in ST-elevation acute myocardial infarction (STEMI) patients with high thrombus burden. Methods We retrospectively analysed myocardial perfusion and cardiac function in 103 acute STEMI patients with HTB (Thrombus score, TS≥2), who underwent pPCI. All patients received standard antithrombotic therapies and initial interventions such as manual thrombus aspiration or balloon dilatation. The immediate stenting group (IS, n=53) received stent placement immediately after angiography if necessary regardless of HTB, while the delayed stenting group (DS, n=50) was deferred for stent implantation for 37 days if TIMI flow was ≥1 at initial angiography or after initial interventions and received enhanced antithrombotic therapy with Tilofiban infusion for 48 h, and thereafter stent implantation was at discretion of the operator based on the residual stenosis in the infarcted related artery. TIMI score (TIMIs), TIMI frame count (TFC) and myocardial blush grade (MBG) were compared immediately after stent implantation for both groups. Results The baseline major clinical characteristics including gender, age, TS and TIMIs were similar in both groups. Immediately after stent implantation, TIMIs, TFC and MBG in the DS group were better than those in IS group (p Conclusions Compared with immediate stenting, delayed stenting seems to improve myocardial perfusion and cardiac function in STEMI patients with high thrombus burden.

Background and Objectives The optimal stenting strategy for the treatment of unprotected left main coronary bifurcation lesions (UPLMCBLs) remains uncertain. Present study observed the technical feasibility and immediate outcomes of the modified culotte stenting (MCS) for the treatment of UPLMCBLs with drug-eluting stents. Methods Forty patients with true UPLMCBLs according Medina9s classification were included in the study. The MCS main steps were described as follows: (1) pre-imbedding a balloon in the larger branch (LB) and stenting the smaller branch (SB) first with mini-protrusion of 1–2 mm into the left main stem, (2) removing the stent balloon out of the SB and wiring the LB via a side-hole of the expanded SB stent, (3) removing the pre-imbedded balloon out of the LB after successfully wiring the LB, (4) deploying the LB stent and rewiring the SB, (5) performing sequential high pressure dilation of each branch followed by a final balloon kissing (FBK). Results The immediate success angiographically (residual stenosis Conclusions MCS for the treatment of UPLMCBLs was technically safe and feasible, readily to complete final balloon kissing, and was associated with high immediate angiographic and procedural success rate.

Background and objectives Circumferential pulmonary vein isolation (CPVI) has become a major treatment of atrial fibrillation (Af). However, the postprocedural early recurrence rate is still high, which may be related to postoperative inflammatory reaction. With pleiotropic effects, statins are expected to inhibit the inflammatory response and thus reduce the Af recurrence after catheter ablation. The authors sought to clarify the efficacy of a large dose of atorvastatin therapy for preventing early Af recurrence after CPVI. Methods A total of 40 patients with paroxysmal Af and with hypercholesterolemia were randomly divided into two groups: control group (n=20) and high-dose atorvastatin intervention group (intervention group, n=20). Both groups received routine clinical medical treatment, and control group only received atorvastatin of £20 mg/day if indicated. Intervention group was given atorvastatin 80 mg 24 h and 40 mg 2 h before CPVI, and then atorvastatin 40 mg/day for 1 month. Blood samples were collected 24 h before and immediately after, 3 days and 1, 2 and 3 months after CPVI. The inflammatory markers including high-sensitivity C reactive protein (hs-CRP), interleukin 6 (IL-6) and tumour necrosis factor α (TNFα), and myocardial injury markers CK-MB and cTn-T were measured. The Af early recurrence was monitored clinically and by 72 h Holter monitoring. Results At a mean follow-up period of 3 months, as compared with the control group, AF burden was significantly reduced in the intervention group (p 0.05). The level of inflammatory markers including hs-CRP, IL-6, TNFα were increased immediately and 3 days after ablation in both groups. However, compared with those of the control group, the levels of hs-CRP, IL-6 and TNFα were significantly reduced in intervention group (p 0.05, each). Conclusions The pilot study showed that high-dose atorvastatin pretreatment and short-term enhanced intervention can reduce the peri-procedural inflammatory response and atrial fibrillation burden after catheter ablation, but does not decrease the early recurrence of atrial fibrillation.

Objective This study was to investigate the outcome of transcatheter closuring large-to-huge ASD with the AOD within one year. Methods 35 consecutive patients with large-to-huge ASD (330 mm) underwent transcatheter defect closure and then were followed up peri-procedurally, at 1-, 6-, and 12-month periods following the operation by clinical assessment, electrocardiographic and echocardiographic examination. All patients received 6-month anti-thromboembolic therapy by using either aspirin or warfarin at the discretion of the operator. The major adverse cardiac events (MACE) include cardiac death, occluder dislodgment leading to urgent cardiac surgery, occluder occupation significantly impeding haemodynamics or cardio-electrical activities, AOD-related thrombo-embolism, AOD-related atrial rupture, the minor adverse cardiac events (MACE) include occluder occupation with or without slight interference of haemodynamics, AOD-related arrhythmia and residual shunting. Results The average diameter of ASD in 35 patients was 33.7±5.2 mm (range 30 mm to 38 mm), and the average diameter of final AOD used was 38.1±7.1 mm (range 32 mm to 42 mm). The immediate technical success was 100% without severe peri-procedural complications. MACE was not found in each stage within a one year follow-up, but MAC Ewas frequently encountered, among which occluder occupation with asympathetic haemodynamic interference occurred 45.7% peri-procedurally, 42.9% at 1-month, 40.0% at 6-month, and 34.3% at 12-month, and AOD-related atrial arrhythmia occurred 51.4% peri-procedurally, 14.3% at 1-month, 8.6% at 6-month, and 2.9% at 12-month. Persistent small residual shunting was found in 24 (68.6%) patients and I°AVB in one (2.9%) patient. Conclusions The large-to-huge ASD can be occluded by using AOD without technical difficulty, but the long-term safety and efficacy requires further study.