Difference between antegrade and retrograde orbital atherectomy system debulking using an artificial pulsatile heart model.

BACKGROUND: Debulking devices are necessary to treat severe calcified lesions. OAS has a unique characteristic that the burr moves forward and backward. There are few studies reporting the differences of ablation style between only-antegrade and only-retrograde OAS. AIMS: The aim of this study was to evaluate the difference of ablation style between only-antegrade and only-retrograde orbital atherectomy system (OAS) using an artificial pulsatile heart model (HEARTROID system®) and optical coherence tomography (OCT). METHODS: The calcified lesion model was inserted into the mid of left anterior descending in the HEARTROID®. Only-antegrade and only-retrograde ablation of OAS were conducted for each five lesions. Pre-OCT, OCT after low speed debulking and OCT after high speed debulking were conducted. The width and the depth of debulked area, the debulked area and the direction of debulked area were investigated. RESULTS: In all of 210 cross-sections, 91 debulked cross sections were chosen for analysis. Only-antegrade group had 47 debulked cross-sections, and only-retrograde group 44 cross-sections. In the evaluation of OCT after high speed debulking, the debulked area (0.76 mm2 [0.58-0.91] vs. 0.53 mm2 [0.36-0.68], p < 0.001) and the depth of debulked area (0.76 mm [0.58-0.91] vs. 0.53 mm [0.36-0.68], p < 0.001) were significantly higher in only-antegrade group compared to only-retrograde group. The debulked bias and the width of debulked area are not significantly different between the two groups. CONCLUSIONS: Compared to only-retrograde debulking, only-antegrade debulking acquired larger debulked area because of larger cutting depth, although the debulked bias and the width of debulked area were comparable between the two groups.

Endoscopic image-guided laser treatment system based on fiber bundle laser steering.

A miniaturized endoscopic laser system with laser steering has great potential to expand the application of minimally invasive laser treatment for micro-lesions inside narrow organs. The conventional systems require separate optical paths for endoscopic imaging and laser steering, which limits their application inside narrower organs. Herein, we present a novel endoscopic image-guided laser treatment system with a thin tip that can access inside narrow organs. The system uses a single fiber bundle to simultaneously acquire endoscopic images and modulate the laser-irradiated area. The insertion and operation of the system in a narrow space were demonstrated using an artificial vascular model. Repeated laser steering along set targets demonstrated accurate laser irradiation within a root-mean-square error of 28 [Formula: see text]m, and static repeatability such that the laser irradiation position was controlled within a 12 [Formula: see text]m radius of dispersion about the mean trajectory. Unexpected irradiation on the distal irradiated plane due to fiber bundle crosstalk was reduced by selecting the appropriate laser input diameter. The laser steering trajectory spatially controlled the photothermal effects, vaporization, and coagulation of chicken liver tissue. This novel system achieves minimally invasive endoscopic laser treatment with high lesion-selectivity in narrow organs, such as the peripheral lung and coronary arteries.

Impact of different coronary angioscopic findings on arterial healing one year after bioresorbable-polymer and second-generation durable-polymer drug-eluting stent implantation.

BACKGROUND: The advantage of using bioresorbable-polymer drug-eluting stent (BP-DES) compared with second-generation durable-polymer drug-eluting stent (2G DP-DES) still remains controversial in clinical situations. The purpose of this study to evaluate the degree of re-endothelialization and the prevalence of high-grade yellow-colored plaque (YCP), which might concern arterial healing after BP-DES and 2G DP-DES implantation using a high-resolution coronary angioscopy (CAS). METHODS: In total, 104 DESs (52: 2G DP-DES and 52: BP-DES) were prospectively observed using CAS 12±1 months after coronary intervention. The grade of neointimal coverage (NIC) over the stent was scored on a 4-point scale from 0 (no coverage) to 3 (complete coverage). YCP grade was also scored on a 4-point scale as 0 (white) to 3 (intensive yellow). High-grade YCP was defined as maximum grade ≥2. Moreover, the prevalence of high-grade YCP and the incidence of thrombus were investigated. RESULTS: BP-DES revealed better dominant NIC grade and less NIC heterogeneity than 2G DP-DES (p=0.0001 and p=0.015, respectively). The prevalence of high-grade YCP was lower for BP-DES than for 2G DP-DES (p=0.05). However, the incidence of thrombus was not significantly different (p=0.41). Multivariate analysis identified that low-density lipoprotein cholesterol levels [odds ratio (OR), 1.03; 95% Confidence Interval (CI): 1.01-1.06, p=0.01] and the usage of BP-DES [OR, 0.36; 95% CI: 0.14-0.91, p=0.03] as independent predictors of high-grade YCP. CONCLUSIONS: Compared with 2G DP-DES, BP-DES was less heterogeneous and well-covered NIC and less prevalence of the high-grade YCP implying optimal arterial healing.

Comparison of neointimal coverage between durable-polymer everolimus-eluting stents and bioresorbable-polymer everolimus-eluting stents 1 year after implantation using high-resolution coronary angioscopy.

OBJECTIVES: We aimed to compare the coronary angioscopic appearance of neointimal coverage (NIC) over durable-polymer everolimus-eluting stents (XIENCE-EES) and bioresorbable-polymer everolimus-eluting stents (SYNERGY-EES) 1 year after implantation. BACKGROUND: XIENCE-EES and SYNERGY-EES have been developed to prevent delayed arterial healing associated with first generation drug-eluting stents. However, the process of arterial healing after XIENCE-EES and SYNERGY-EES implantation has not been clarified. METHODS: Patients who underwent implantation of XIENCE-EES (n = 20) or SYNERGY-EES (n = 20) were enrolled in this study. Coronary angiography and coronary angioscopy were performed 12 ± 1 months after stent implantation. The NIC over the stent was classified into four grades: grade 0, stent struts fully exposed; grade 1, stent struts bulging into the lumen and, still visible; grade 2, stent struts embedded in neointima but still visible; and grade 3, stent struts fully embedded and invisible. Stents exhibiting more than one NIC grade was defined as heterogeneous. Moreover, presence of thrombi was investigated. RESULTS: The distribution of dominant NIC grade (XIENCE-EES: grade 0, 0%; grade 1, 25%; grade 2, 50%; grade 3, 25%; SYNERGY-EES: grade 0, 0%; grade 1, 5%; grade 2, 15%; grade 3, 80%; P = 0.002) and NIC heterogeneity was significantly different (P = 0.004). Thrombi were more frequent in XIENCE-EES than in SYNERGY-EES (40 versus 10%, respectively; P = 0.03). CONCLUSION: Compared with XIENCE-EES, SYNERGY-EES were well covered by neointima and accompanied by fewer thrombi. These findings implied arterial healing of SYNERGY-EES was better than that of XIENCE-EES.

Refractory Vascular Wall Healing after Paclitaxel-Coated Nitinol Stent Implantation in the Femoropopliteal Artery: A High-Resolution Angioscopic Assessment.

It is unclear whether arterial healing occurs beyond 1 year following paclitaxel-coated stent implantation in peripheral artery disease. An 81-year-old woman with superficial femoral artery disease underwent endovascular therapy with a paclitaxel-coated stent. An angiography 21 months later revealed peri-stent contrast staining in the superficial femoral artery, and optical frequency domain imaging demonstrated incomplete stent apposition with significant positive vascular remodeling. High-resolution angioscopy detected positive vascular wall remodeling and in-stent yellow plaque more clearly than conventional angioscopy. Refractory superficial femoral arterial wall healing was apparent more than 20 months after paclitaxel-coated stent implantation.

Endovascular therapy for subclavian artery restenosis due to stent strut protrusion with high-resolution angioscopy and three-dimensional optical frequency domain imaging.

A 47-year-old female patient was admitted with a complaint of severe chest pain on effort. She had a history of effort angina treated using coronary artery bypass with left internal thoracic arterial bypass to the left ascending coronary artery. She also had left subclavian and vertebral arterial stenoses, which were treated with balloon-expandable stents. Exercise stress myocardial perfusion imaging revealed anterior to apex left ventricular myocardial ischemia. Cardiac ischemia due to left subclavian stenosis was diagnosed. We treated the left subclavian arterial stenosis with endovascular therapy. We observed that the vertebral Palmaz stent protruded from the ostium and the jailed subclavian artery on high-resolution angioscopy (Zemporshe with a 0.48-megapixel equivalent resolution; Taisho Biomed Instruments, Osaka, Japan) and optical frequency domain imaging (OFDI). A guide wire was successfully crossed through the Palmaz stent strut, which was confirmed using three-dimensional OFDI. The stent strut was dilated using balloon angioplasty. New imaging technologies are promising tools for improving the efficacy and safety of craniocervical intervention. .

Selective Blockade of Periostin Exon 17 Preserves Cardiac Performance in Acute Myocardial Infarction.

We previously reported that overexpression of full-length periostin, Pn-1, resulted in ventricular dilation with enhanced interstitial collagen deposition in a rat model. However, other reports have documented that the short-form splice variants Pn-2 (lacking exon 17) and Pn-4 (lacking exons 17 and 21) promoted cardiac repair by angiogenesis and prevented cardiac rupture after acute myocardial infarction. The apparently differing findings from those reports prompted us to use a neutralizing antibody to selectively inhibit Pn-1 by blockade of exon 17 in a rat acute myocardial infarction model. Administration of Pn neutralizing antibody resulted in a significant decrease in the infarcted and fibrotic areas of the myocardium, which prevented ventricular wall thinning and dilatation. The inhibition of fibrosis by Pn neutralizing antibody was associated with a significant decrease in gene expression of fibrotic markers, including collagen I, collagen III, and transforming growth factor-ß1. Importantly, the number of α-smooth muscle actin-positive myofibroblasts was significantly reduced in the hearts of animals treated with Pn neutralizing antibody, whereas cardiomyocyte proliferation and angiogenesis were comparable in the IgG and neutralizing antibody groups. Moreover, the level of Pn-1 expression was significantly correlated with the severity of myocardial infarction. In addition, Pn-1, but not Pn-2 or Pn-4, inhibited fibroblast and myocyte attachment, which might account for the cell slippage observed during cardiac remodeling. Collectively, these results indicate that therapeutics that specifically inhibit Pn exon-17, via a neutralizing antibody or drug, without suppressing other periostin variants might offer a new class of medication for the treatment of acute myocardial infarction patients.

A novel homemade snare, safe, economical and size-adjustable.

AIMS: Snaring has recently been reported as being effective in catching the retrograde guidewire (GW) in retrograde percutaneous coronary intervention (PCI) for chronic total occlusion. However, commercially available snares and previously reported homemade snares have a number of drawbacks, such as additional cost, limited size adjustability, risk of vessel injury and difficult handling. We report here a novel method to create easily an inexpensive, safe and size-adjustable snare. METHODS AND RESULTS: Our newly developed homemade snare consists of a conventional 0.014" GW, a PCI balloon, and a guiding catheter (GC). In most cases, no extra cost is needed. As the snare is created by the soft wire tip, vascular injury is negligible. To adjust the size of the snare loop, the snare wire is simply pulled backwards and pushed forwards. Using this snare technique, we succeeded in the total revascularisation of a CTO in the left main trunk with a retrograde approach. CONCLUSIONS: We report a novel method to create easily an inexpensive, safe and size-adjustable snare, and demonstrate its use in a retrograde CTO intervention. In some cases where a conventional snare is indicated, such as removal of intravascular iatrogenic foreign bodies, this novel homemade snare would be preferable because of its advantages.

Inhibition of Lp(a)-induced functional impairment of endothelial cells and endothelial progenitor cells by hepatocyte growth factor.

BACKGROUND: Lipoprotein (a) (Lp(a)) is one of the risk factors for peripheral artery disease (PAD). Our previous report demonstrated that hepatocyte growth factor (HGF) gene therapy attenuated the impairment of collateral formation in Lp(a) transgenic mice. Since risk factors for atherosclerosis accelerate endothelial senescence and impair angiogenesis, we examined the role of Lp(a) in dysfunction and senescence of endothelial progenitor cells (EPC) and endothelial cells. METHODS: In vitro and in vivo incorporation assays were performed using ex-vivo expanded DiI-labeled human EPC. Senescence of cultured endothelial cells, production of oxidative stress and angiogenesis function were evaluated by SA-ß-galactosidase staining, dihydroethidium (DHE) staining and Matrigel assay, respectively. RESULTS: EPC transplantation significantly stimulated recovery of ischemic limb perfusion, while EPC pre-treated with Lp(a) did not increase ischemic limb perfusion. Impairment of angiogenesis by EPC with Lp(a) was associated with a significant decrease in CD31-positive capillaries and DiI-labeled EPC. Importantly, Lp(a) significantly accelerated the onset of senescence and production of reactive oxygen species (ROS) in human aortic endothelial cells, accompanied by a significant increase in the protein expression of p53 and p21. On the other hand, HGF significantly attenuated EPC dysfunction, senescence, ROS production, and p53 and p21 expression induced by Lp(a). CONCLUSION: Lp(a) might affect atherosclerosis via acceleration of senescence, ROS production, and functional impairment of the endothelial cell lineage. HGF might have inhibitory effects on these atherogenic actions of Lp(a).

Hepatocyte growth factor reduces cardiac fibrosis by inhibiting endothelial-mesenchymal transition.

The purpose of this study was to investigate the effect of hepatocyte growth factor (HGF) on the pathogenesis of cardiac fibrosis induced by pressure overload in mice. Although cardiac fibrosis is attributed to excess pathological deposition of extracellular matrix components, the mechanism remains unclear. Recent reports revealed that α-smooth muscle actin-expressing myofibroblasts are primarily responsible for fibrosis. It is believed that myofibroblasts are differentiated from resident fibroblasts, whereas the transformation of vascular endothelial cells into myofibroblasts, known as endothelial-mesenchymal transition, has been suggested to be intimately associated with perivascular fibrosis. Thus, we hypothesized that HGF prevents cardiac fibrosis by blocking these pathways. We analyzed the pressure-overloaded HGF-transgenic mouse model made by transverse aortic constriction. Human coronary artery endothelial cells and human cardiac fibroblasts were examined in vitro after being treated with transforming growth factor-ß1 or angiotensin II with or without HGF. The amount of cardiac fibrosis significantly decreased in pressure-overloaded HGF-transgenic mice compared with pressure-overloaded nontransgenic controls, particularly in the perivascular region. This was accompanied by a reduction in the expression levels of fibrosis-related genes and by significant preservation of echocardiographic measurements of cardiac function in the HGF-transgenic mice (P<0.05). The survival rate 2 months after transverse aortic constriction was higher by 45% (P<0.05). HGF inhibited the differentiation of human coronary artery endothelial cells into myofibroblasts induced by transforming growth factor-ß1 and the phenotypic conversion of human cardiac fibroblasts into myofibroblasts. We conclude that HGF reduced cardiac fibrosis by inhibiting endothelial-mesenchymal transition and the transformation of fibroblasts into myofibroblasts.

Telmisartan exerts renoprotective actions via peroxisome proliferator-activated receptor-γ/hepatocyte growth factor pathway independent of angiotensin II type 1 receptor blockade.

Angiotensin (Ang) II type 1 receptor blockers have demonstrated beneficial effects beyond blood pressure control in the treatment of chronic kidney disease. There is clinical evidence that telmisartan is more effective than losartan in reducing proteinuria in hypertensive patients with diabetic nephropathy, because it is a partial agonist of peroxisome-proliferator activated receptor-γ (PPARγ), as well as an Ang II type 1 receptor blocker (AMADEO Study [A comparison of telMisartan versus losArtan in hypertensive type 2 DiabEtic patients with Overt nephropathy]). In this study, we examined the role of PPARγ activation in the renal protective actions of telmisartan using Ang II type 1 receptor-deficient mice. Renal injury was induced in Ang II type 1 receptor-deficient mice by producing unilateral ureteral obstruction, which exhibited severe renal interstitial fibrosis and inflammation. In these mice, telmisartan prevented hydronephrosis induced by unilateral ureteral obstruction more strongly than did losartan. Importantly, the prevention of renal atrophy and fibrosis by telmisartan was significantly attenuated by GW9662, a PPARγ antagonist. Interestingly, the downstream effector of PPARγ activation by telmisartan is hepatocyte growth factor (HGF), a well-known antifibrotic factor, because renal HGF expression was significantly increased by telmisartan, and a neutralizing antibody against HGF diminished the renal protective action of telmisartan. These beneficial changes by telmisartan were associated with a decrease in the expression of transforming growth factor-ß1 and other proinflammatory and profibrotic cytokine genes through PPARγ/HGF activation. Our findings provide evidence of organ protective actions of telmisartan through the PPARγ/HGF pathway, independent of Ang II type 1 receptor blockade. Further development of the next generation of Ang II type 1 receptor blockers with added organ protective actions, such as PPARγ activation, might provide new beneficial drugs to treat renal and cardiovascular diseases.

Role of serotonin in angiogenesis: induction of angiogenesis by sarpogrelate via endothelial 5-HT1B/Akt/eNOS pathway in diabetic mice.

Serotonin (5-hydroxytryptamine, 5-HT) plays a crucial role in peripheral artery disease (PAD) and diabetes mellitus (DM). In these conditions, the balance between the 5-HT2A receptor in smooth muscle cells and the 5-HT1B receptor in endothelial cells (ECs) regulates vascular tonus. In the present study, we focused on the role of 5-HT in endothelial dysfunction using a selective 5-HT2A receptor blocker, sarpogrelate. In human EC, 5-HT markedly stimulated eNOS expression and the phosphorylation of eNOS, Akt and ERK1/2. In addition, a dose-dependent increase in tubule-formation on Matrigel was observed after 5-HT treatment. In contrast, high glucose significantly inhibited tubule formation and eNOS expression through inactivation of Akt, while 5-HT significantly attenuated these actions of high glucose (P<0.01). These results indicate that 5-HT stimulated angiogenesis through activation of Akt in ECs. However, in clinical situations, 5-HT seems to act as the "devil". To examine the role of 5-HT in diabetic PAD, a hindlimb ischemia model was created in diabetic mice. The blood flow ratio of the ischemic to non-ischemic limb was significantly lower in DM mice than in normal mice, while sarpogrelate significantly attenuated the decrease in the blood flow ratio compared to control (P<0.01). Consistently, the decrease in eNOS expression and Akt activity in DM mice was significantly attenuated by sarpogrelate. Overall, the present study demonstrated that selective inhibition of 5-HT2A by sarpogrelate significantly restored ischemic limb blood perfusion in a severe diabetic mouse model through stimulation of the eNOS/Akt pathway via the endothelial 5-HT1B receptor. Enhancement of vasodilation and angiogenesis by sarpogrelate might provide a unique treatment for PAD and DM patients.