Rosiglitazone Alleviates Contrast-Induced Acute Kidney Injury in Rats via the PPARγ/NLRP3 Signaling Pathway.

Background: This study investigated the effect and mechanism of rosiglitazone on a rat model with contrast-induced acute kidney injury (CI-AKI). Materials and Methods: The CI-AKI rat model was established from Sprague Dawley rats by furosemide injection (10 ml/kg) to the caudal vein followed by iohexol (11.7 ml/kg). The experimental grouping was randomly allocated into control, model, rosiglitazone, and T0070907 groups. Blood samples were collected from the abdominal aorta. Serum creatinine, urea nitrogen, MDA, and SOD contents were detected by biochemical analysis. TNF-α and IL-10 expression was detected by ELISA. Urine creatinine and urine protein were measured following 24-h urine biochemistry testing. Cell pathology and apoptosis were detected by H&E and TUNEL staining, respectively. PPARγ, NLRP3, eNOS, and caspase-3 mRNA expression were detected by qPCR. Caspase-3 and NLRP3 expression were detected by immunohistochemistry. Results: The CI-AKI rat model was successfully established because the results showed that compared with control, serum creatinine, urea nitrogen, MDA, SOD, TNF-α, and IL-10, urine creatinine and urine protein levels were significantly increased in the model group, indicating AKI, but was significantly decreased with rosiglitazone treatment, indicating recovery from injury, while opposite results were obtained with SOD. Apoptosis rate was significantly increased in the model group and significantly decreased with rosiglitazone treatment. NLRP3 and eNOS increased significantly in the model group and decreased significantly with rosiglitazone treatment, while opposite results were obtained with PPARγ. NLRP3 and caspase-3 protein expression was significantly increased in the model group and significantly decreased with rosiglitazone treatment. Conclusion: Rosiglitazone could alleviate acute renal injury in the CI-AKI rat model by regulating the PPARγ/NLRP3 signaling pathway and should be further investigated as a potential treatment in clinical studies.

Efficacy and Biosafety of a New Bioresorbable Vascular Scaffold Covered with Biodegradable Film in Rabbits: An In Vivo Study.

BACKGROUND: We developed a new fully bioresorbable vascular scaffold covered with biodegradable poly-L-lactic acid film (Firesorb-C) for coronary artery perforation. Our vitro tests have demonstrated that Firesorb-C was technically feasible but its biosafety and efficacy warranted further validation in vivo. OBJECTIVE: The aim of this study was to evaluate the biosafety and efficacy of Firesorb-C in rabbits. METHODS: Firesorb-C was deployed at the zone from the abdominal aorta to the right iliac artery in five rabbits. Angiography was conducted for evaluation of the immediate efficacy and 6-month biosafety and biodegradability of the Firesorb-C. Meanwhile, optical coherence tomography (OCT), histological light microscopy (HLM) and scan electron microscopy (SEM) were performed to evaluate the biosafety. RESULTS: All Firesorb-C applications were successfully implanted without procedure-related complications. In all treated rabbits, angiography showed that the Firesorb-C had completely sealed the opening of the left iliac artery without blood flow in its branches but with full patency of the right iliac artery immediately post-procedurally, while the covered membrane of Firesorb-C had been degraded and blood flow was restored in the left iliac artery and its branches at 6 months. OCT also found that the occluded left iliac artery had been reopened and the stented segment was almost fully endothelialized without in-stent restenosis at 6 months, meanwhile HLM and SEM confirmed comparable results. CONCLUSIONS: Firesorb-C is associated with excellent efficacy, biosafety and biodegradability in rabbits. It shows promise as a replacement for conventional covered stents for treatment of coronary artery perforation or for use in other clinical situations.

Exosomes isolated from the plasma of remote ischemic conditioning rats improved cardiac function and angiogenesis after myocardial infarction through targeting Hsp70.

Remote ischemic conditioning (RIC) is a promising therapeutic strategy to protect heart against ischemic-reperfusion injury. Exosomes have been proved to be an important regulator in many pathological processes. Whether the exosomes derived from RIC could improve cardiac remodeling and function after myocardial infarction (MI) has not been reported. MI animal model was established by ligating the left coronary artery. The bilateral hindlimbs of rats were subjected to RIC treatment using tourniquets. Exosomes were isolated from the plasma of RIC rats and identified by transmission electron microscope. The proliferation, migration, and apoptosis of endothelial cells were measured by CCK8, traswell, and flow cytometry. Western blotting, and qRT-PCR were applied to measure the expression of angiogenesis-related molecules, and immunohistochemistry staining was used to observe the expression of vWF. RIC and RIC exosomes remarkably facilitated cardiac function, cardiac cell remodeling, and angiogenesis. RIC exosomes markedly increased the cell ratio in the G1 phase, cell migration, cell proliferation, tube formation, and inhibited cell apoptosis through Hsp70. The expression of eNOS, iNOS, HIF-1α, Ang-1, and VEGF was markedly increased by RIC exosomes. RIC exosomes significantly improved cardiac function, cardiac remodeling, and angiogenesis after MI, and they accelerated angiogenesis through increasing the levels of angiogenesis-related molecules.

Comparative Analysis of Three Different Optimization Procedures for Coronary Bifurcation Provisional Stenting: Insights from Micro-Computed Tomography and Optical Coherence Tomography Imaging of Bench Deployments.

Background: Post-dilation with kissing balloon dilation remains controversial in the 1-stent approach, but many technical improvements are possible to refine the final results. This study aimed to evaluate the results of different side-branch (SB) ostial treatments after main vessel stenting, including ostial optimization technique (OOT), simultaneous kissing balloon dilation (KBD) and single balloon dilation (SBD). Methods: Three different ostial side branch treatments (OOT, n = 6; KBD, n = 6; SBD, n = 6) were emulated in a synthetic bifurcated phantom using a second-generation sirolimus-eluting stent (Firebird2TM, Microport, Shanghai, China). Micro-computed tomography (micro-CT) and optical coherence tomography (OCT) were performed to assess morphologies. Results: Compared to the non-OOT procedures (SBD and KBD), OOT was characterized by the sequential dilation of two snuggling balloons, creating a longer valgus struts length (OOT: 2.13 ± 0.30 mm, SBD: 1.23 ± 0.34 mm, KBD: 1.11 ± 0.39 mm, p < 0.01), broader angulation between the main-branch and valgus struts axes (OOT: 42.72 ± 0.91°, SBD: 25.77 ± 7.81°, KBD: 31.78 ± 1.34°, p < 0.01), shorter neocarina length (OOT: 0.28 ± 0.31 mm, SBD: 0.64 ± 0.38 mm, KBD: 1.11 ± 0.37 mm, p < 0.01), larger SB ostial area (OOT: 6.76 ± 0.17 mm2, SBD: 4.78 ± 0.86 mm2, KBD: 5.87 ± 0.89 mm2, p < 0.01), and lower index of stent cell distortion (OOT: 6.67 ± 3.33%, SBD: 10.67 ± 4.23%, KBD: 20.00 ± 5.29%, p < 0.01). In addition, the rate of severe strut malapposition was lower with the OOT procedure compared with the non-OOT procedures (OOT: 2.22 ± 0.48%, SBD: 10.31 ± 0.66%, KBD: 6.74 ± 1.24%, p < 0.01). Conclusions: OOT, consisting of an initial proximal optimizing technique (POT) and sequential snuggling balloon dilation and then re-POT, significantly optimized the results of provisional bifurcation treatment. The physiological and clinical significance of our observations await further clarification.

Branch ostial optimization treatment and optimized provisional t-stenting with polymeric bioresorbable scaffolds: Ex-vivo morphologic and hemodynamic examination.

The optimal side-branch (SB) ostium treatment after provisional side-branch scaffolding remains a subject of debate in bioresorbable vascular scaffold (BVS) era. In this study, we evaluated a novel optimized provisional T-stenting technique (OPT) and assessed its feasibility by comparison with T and small protrusion technique (TAP).Two provisional SB scaffolding techniques (OPT, n = 5; TAP, n = 5) were performed using polymeric BVS in a bifurcated phantom. The sequential intermediate snuggling balloon dilation, also called ostial optimal technique, was added to OPT but not TAP to dilate the side-branch ostium while the final snuggling balloon dilation applied for both procedures. Microcomputed tomography (microCT) and optical coherence tomography (OCT) were performed to assess morphology, and computational fluid dynamics (CFD) was performed to assess hemodynamics in the scaffolded bifurcations. Compared with TAP in microCT analysis, OPT created shorter neo-carina length than TAP (0.34 ±â€Š0.10 mm vs 1.02 ±â€Š0.26 mm, P < .01), longer valgus struts length (2.49 ±â€Š0.27 mm vs 1.78 ±â€Š0.33 mm, P < .01) with larger MB ostial area (9.46 ±â€Š0.04 mm vs 8.34 ±â€Š0.09 mm, P < .01). OCT found that OPT significantly decreased the struts mal-apposition (13.20 ±â€Š0.16% vs 1.94 ±â€Š0.54%, P < .01). CFD revealed that OPT generated more favorable flow pattern than TAP, as indicated by less percent (4.68 ±â€Š1.40% vs 8.88 ±â€Š1.21%, P < .01) of low wall shear stress (<0.4 Pa) along the lateral walls.By using BVSs for bifurcation intervention, the sequential intermediate snuggling balloon dilation is feasible for optimizing ostial SB and facilitating subsequent SB scaffolding. Results show OPT is better than TAP for bifurcated morphology and hemodynamics in this ex-vivo study.

Ex vivo mono-ring technique simplifies culotte stenting for treatment of true bifurcation lesions: Insights from bench testing and clinical application.

BACKGROUND: Despite various culotte-based stenting techniques available clinically, the optimal one remains undetermined. The study aimed to test whether ex vivo mono-ring culotte stenting (MRC) was technically feasible and superior to mini culotte stenting (MCS) in treatment of coronary bifurcation lesions. METHODS: Mono-ring culotte stenting was characterized by ex vivo wiring of the most proximal cell of the side branch (SB) stent to ensure a mono-ring result of the culotte stenting. Comparison of MRC vs. MCS in treatment of true bifurcation lesions was performed in vitro (n = 15 for each group) and in clinical case-controlled study with propensity matching at a ratio of 1:2 (n = 21 for MRC group; n = 42 for MCS group). RESULTS: Compared to MCS, MRC had lower incidence of stent under-expansion band (0% vs. 53.3%, p = 0.002) and less residual ostial area stenosis of SB (9.2 ± 9.0% vs. 20.0 ± 14.8%, p = 0.023), as assessed in vitro by micro-computed tomography. In a case-controlled study, no adverse cardiac events were observed in the MRC group. The procedural success was similar between MRC and MCS (100% vs. 95.2%, p = 0.548), but MRC had less residual ostial stenosis of the SB (8.7% ± 11.0% vs. 16.8% ± 11.2%, p = 0.008), lower procedural (33.3 ± 9.5 min vs. 46.7 ± 15.6 min, p = 0.001) and fluoroscopic (19.7 ± 4.9 min vs. 26.2 ± 7.1 min, p < 0.001) time, and less contrast use (114.3 ± 28.9 mL vs. 156.5 ± 56.4 mL, p = 0.002). CONCLUSIONS: Mono-ring culotte stenting as compared to MCS is associated with better bifurcation stent morphology, less procedural complexity and residual ostial SB stenosis.

Benefit of standard versus low-dose tirofiban for percutaneous coronary intervention in very elderly patients with high-risk acute coronary syndrome.

AIM: This study aimed to compare the efficacy and safety between standard and low-dose tirofiban in the treatment of elderly high-risk non-ST-segment elevation acute coronary syndrome (NSTE-ACS) patients who underwent percutaneous coronary intervention (PCI). METHODS: Ninety-four very elderly (>or=80 years) high-risk patients with NSTE-ACS were randomly assigned to the standard or the low-dose group. Upstream tirofiban was administered intravenously with a bolus dose of 0.4 microg x kg(-1) x min(-1) over a period of 30 min after the diagnosis had been confirmed, and was followed by a 36-48 h infusion of 0.10 microg x kg(-1) x min(-1) or 0.075 microg x kg(-1) x min(-1). PCI was performed within 24 h of admission. Platelet aggregation inhibition and thrombolysis in myocardial infarction (TIMI) grade flow were assessed. The major adverse cardiac events (MACEs), including death, myocardial infarction, recurrent angina and urgent target-vessel revascularization (TVR), were documented at 7 d, 30 d, and 6 months, and bleeding events were recorded at 7 d. RESULTS: Although a significantly higher inhibition of platelet aggregation was observed in the standard-dose group (P<0.05), angiographic PCI success was similar between the two groups (P>0.05). The rate of MACEs was not significantly different at 7 days (2.1% vs 4.4%, P=0.61), 30 days (6.3% vs 8.7%, P=0.71) and 6 months (14.6% vs 17.4%, P=0.71). Major bleeding events were significantly higher in the standard-dose group (10.4% vs 0.0%, P=0.03). CONCLUSION: In very elderly high-risk patients with NSTE-ACS undergoing PCI, low-dose tirofiban offered about the same level of protection from major ischemic events that standard doses did, with less associated bleeding.

Firebird and cypher sirolimus-eluting stents and bare metal stents in treatment of very long coronary lesions.

BACKGROUND: As a kind of sirolimus-eluting stent (SES) made in China, Firebird SES is more effective than bare metal stent (BMS) and not inferior to Cypher SES for short coronary lesions in terms of reduction of restenosis and revascularization. However, Firebird SES does not show any benefits in patients with a very long coronary lesion (VLCL). The present study was undertaken to evaluate the safety and efficacy of Firebird SES for VLCL by comparison of Cypher SES and BMS. METHODS: In this prospective, nonrandomized and comparative study, eligible patients with de novo coronary lesion (> or = 30 mm) between January 2005 and June 2006 were allocated into Firebird SES group, Cypher SES group or BMS group. They were subjected to an angiographic follow-up of 6 months and a clinical follow-up of 12 months. The primary endpoints constitute the in-stent and in-segment restenosis rates at 6 months. The secondary endpoint was defined as a major adverse cardiovascular event (MACE) that was a 12-month combined endpoint of all-cause deaths, reinfarction or in-stent thrombosis, and target-lesion revascularization. The 12-month in-stent thrombosis was also evaluated to address the safety of Firebird SES implantation exceptionally. RESULTS: A total of 468 patients were assessed for eligibility. Of 113 patients who were finally included according to the prior inclusion and exclusion criteria, 39 (41 lesions) were treated with Firebird SES, 37 (39 lesions) with Cypher SES, and 37 (37 lesions) with BMS. There were no significant differences in the baseline characteristics between the three groups; but there were longer lesions, more frequent use of overlapping stent in the Firebird SES group and the Cypher SES group. Angiographic follow-up showed that the rates of binary stenosis were similar between the Firebird SES group and the Cypher SES group (in-segment: 14.6% vs 12.8%, relative risk (RR) 1.14, P = 0.81; in-stent: 9.8% vs 10.3%, RR 0.95, P = 0.94), and significantly lower than those in the BMS group (in-segment: vs. 36.1%, RR 0.41 or 0.36, P = 0.04 or 0.03, respectively; in-stent: vs 30.6%, RR 0.32 or 0.34, P = 0.03 or 0.04, respectively). The total MACE rate up to 12 months was also similar in both SES groups (7.7% vs 5.4%, P = 1.000), and significantly lower than that in the BMS group (27.0%, P = 0.034 or 0.024, respectively). The in-stent thrombosis rate in the follow-up period was 2.6% in the Firebird SES group, not higher in the Cypher SES and BMS groups (2.7% and 2.7%, respectively, P = 1.000). CONCLUSIONS: In the treatment of VLCL, Firebird SES would be safer and more effective than BMS. Firebird SES may be not inferior to Cypher SES in terms of restenosis and MACE.