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Coronary chronic total occlusion (CTO) is a frequent finding in patients with coronary artery disease. It remains one of the most challenging subsets, accounting for 10-20% of all percutaneous coronary interventions (PCI). Although remarkable progress in PCI has been made, it is reasonable to state that successful recanalization of CTO represents the “last frontier" of PCI. PCI of CTOs has been limited historically by technical success rates of 50-70%. The introduction of enhanced guidewires, microcatheter, channel dilatator with increasing operator experience, and innovative techniques such as the retrograde approach have raised hopes for better outcomes. This article goes into depth into various strategies of retrograde approach in CTO.By convention, a total obstruction of the coronary artery with no flow at the occluded segment that has been present for at least 3 months is termed as chronic total occlusion or CTO. This is to be distinguished from a sudden occlusion of the coronary artery lumen by a thrombus during an acute myocardial infarction. Percutaneous coronary intervention (PCI) of CTO is increasingly being performed by interventional cardiologists with improved success rates. In this article, the focus will be on antegrade techniques that will assist the operator to maximise the success rates and to minimise the complications.Despite major advances in coronary intervention, the recanalization of a chronic total occlusion (CTO) remains a challenge for many interventional cardiologists. Complex anatomy and lesion characteristics demand a special set of skills for procedural success. Provided patient selection is appropriate, CTO intervention can confer a variety of benefits including relief of angina, improvement in left ventricular function and reduction in ischemic burden. The chances of procedural success are enhanced by having a dedicated CTO program. This involves adequate training of staff, quality control and availability of equipment. A diverse toolkit allows variation in strategy and increases procedural success. Further, skills and equipment are required to manage complications like vessel dissection, perforation and the resultant ischemic or mechanical complications. These procedures can often be lengthy and giving careful consideration to peri-procedural issues like radiation exposure and contrast dose plays a vital role in ensuring optimal patient outcomes and radiation hygiene. In this article we review the evidence behind indications for CTO intervention and discuss the development of a CTO program.Percutaneous coronary intervention of chronically occluded vessels can result in significant improvement in symptoms, relieve myocardial ischemia, and affect a reduction in major adverse cardiac events. Likelihood of achieving successful revascularization can be significantly enhanced with a thorough understanding of the pathology of these occluded coronary arteries. In this chapter, various steps and techniques to cross the CTO lesion and recanalize it are discussed in details.During percutaneous coronary interventions (PCI) for chronic total occlusion (CTO), prolonged procedures increase the risk of excessive radiation exposure. These situations harbor a major concern to protect patients and personnel in the cardiac interventional laboratory (CCL). Important questions regarding radiation safety for interventional cardiologists performing PCI for CTO lesions are discussed and concrete applications are suggested.Human coronary collaterals are inter-coronary communications that are believed to be present from birth. In the presence of chronic total occlusions, recruitment of flow via these collateral anastomoses to the arterial segment distal to occlusion provide an alternative source of blood flow to the myocardial segment at risk. This mitigates the ischemic injury. Clinical outcome of coronary occlusion ie. severity of myocardial infarction/ischemia, impairment of cardiac function and possibly survival depends not only on the acuity of the occlusion, extent of jeopardized myocardium, duration of ischemia but also to the adequacy of collateral circulation. Adequacy of collateral circulation can be assessed by various methods. These coronary collateral channels have been used successfully as a retrograde access route for percutaneous recanalization of chronic total occlusions. Factors that promote angiogenesis and further collateral remodeling ie. arteriogenesis have been identified. Promotion of collateral growth as a therapeutic target in patients with no suitable revascularization option is an exciting proposal.The "hybrid" approach to chronic total occlusion (CTO) percutaneous coronary intervention (PCI) was developed to provide guidance on optimal crossing strategy selection. Dual angiography remains the cornerstone of clinical decision making in CTO PCI. Four angiographic parameters are assessed (a) morphology of the proximal cap (clear-cut or ambiguous); (b) occlusion length; (c) distal vessel size and presence of bifurcations beyond the distal cap; and (d) location and suitability of location and suitability of a retrograde conduit (collateral channels or bypass grafts) for retrograde access. Antegrade wire escalation is favored for short ( less then 20 mm) occlusions, usually escalating rapidly from a soft tapered-tip polymer-jacketed guidewire to a stiff polymer-jacketed or tapered-tip guidewire. Antegrade dissection/re-entry is favored in long (≥20 mm long) occlusions, trying to minimize the dissection length by re-entering into the distal true lumen immediately after the occlusion. Primary retrograde approach is preferred for lesions with an ambiguous proximal cap, poor distal target, good interventional collaterals, and heavy calcification,as well as chronic kidney disease. The "hybrid" approach advocates early change between strategies to enable CTO crossing in the most efficacious, efficient, and safe way. Several early studies are demonstrating high success and low complication rates with use of the "hybrid" approach, supporting its expanding use in CTO PCI.This study aimed to comprehend the largely unknown role of voltage-gated potassium channel 1.3 (Kv1.3) in the phagocytic function of macrophages. We found that blocking of the Kv1.3 channel with 100 pmol L(-1) Stichodactyla helianthus neurotoxin (ShK) enhanced the phagocytic capacities of both resting and lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages in the chicken erythrocyte system. In the fluorescein isothiocyanate (FITC)-labeled Escherichia coli k-12 system, ShK increased the phagocytic capacities of resting RAW264.7 cells, but not of the LPS-stimulated cells, as LPS alone stimulated almost saturated phagocytosis of the macrophages. ShK increased the nitric oxide (NO) production in LPS-activated cells, but not in resting RAW264.7 cells. There was no effect of ShK alone on the cytokine secretions in resting RAW264.7 cells, but it suppressed IL-1β secretion in LPS-stimulated RAW264.7 cells. At a concentration of 100 pmol L(-1), ShK did not affect the viability of the tested cells. Kv1.3 was expressed in RAW264.7 cells; this expression was downregulated by LPS, but significantly upregulated by disrupting caveolin-dependent endocytosis with filipin III. In addition, cytochalasin D, an inhibitor of actin polymerization, did not affect the Kv1.3 expression. Thus, blocking of the Kv1.3 channel enhances the phagocytic capacity and NO production of this cell line. Our results suggest that Kv1.3 channel serves as a negative regulator of phagocytosis in macrophages and can therefore be a potential target in the treatment of macrophage dysfunction.Cell mechanics plays an important role in cellular physiological activities. Recent studies have shown that cellular mechanical properties are novel biomarkers for indicating the cell states. In this article, temperature-controllable atomic force microscopy (AFM) was applied to quantitatively investigate the effects of temperature and cellular interactions on the mechanics and morphology of human cancer cells. First, AFM indenting experiments were performed on six types of human cells to investigate the changes of cellular Young's modulus at different temperatures and the results showed that the mechanical responses to the changes of temperature were variable for different types of cancer cells. Second, AFM imaging experiments were performed to observe the morphological changes in living cells at different temperatures and the results showed the significant changes of cell morphology caused by the alterations of temperature. Finally, by co-culturing human cancer cells with human immune cells, the mechanical and morphological changes in cancer cells were investigated. The results showed that the co-culture of cancer cells and immune cells could cause the distinct mechanical changes in cancer cells, but no significant morphological differences were observed. The experimental results improved our understanding of the effects of temperature and cellular interactions on the mechanics and morphology of cancer cells.This study explored the effects of cucurbitacin E (CuE), a bioactive compound from Cucurbitaceae, on the metabolism/pharmacokinetic of tolbutamide, a model CYP2C9/11 probe substrate, and hepatic CYP2C11 expression in rats. Liquid chromatography-(tandem) mass spectrometry (LC-MS/MS) assay was used to detect tolbutamide as well as 4-hydroxytolbutamide, and then successfully applied to the pharmacokinetic study of tolbutamide in rats. The effect of CuE on CYP2C11 expression was determined by western blot. TGF beta inhibitor CuE (1.25-100 μmol L-1) competitively inhibited tolbutamide 4-hydroxylation (CYP2C11) activity only in concentration-dependent manner with a K i value of 55.5 μmol L-1 in vitro. In whole animal studies, no significant difference in metabolism/pharmacokinetic of tolbutamide was found for the single pretreatment groups. In contrast, multiple pretreatments of CuE (200 μg kg-1 d-1, 3 d, i.p.) significantly decreased tolbutamide clearance (CL) by 25% and prolonged plasma half-time (T 1/2) by 37%. Moreover, CuE treatment (50-200 μg kg-1 d-1, i.p.) for 3 d did not affect CYP2C11 expression. These findings demonstrated that CuE competitively inhibited the metabolism of CYP2C11 substrates but had no effect on rat CYP2C11 expression. This study may provide a useful reference for the reasonable and safe use of herbal or natural products containing CuE to avoid unnecessary drug-drug interactions.
Kidney dysfunction is reportedly associated with adverse outcome in patients with peripheral artery disease (PAD). Estimated glomerular filtration rate (eGFR), a recently popularized index for assessing kidney function, is calculated using serum creatinine or cystatin C. Compared with creatinine-based eGFR (eGFRcr), cystatin C-based eGFR (eGFRcys) is less affected by age, gender, and muscle mass. We hypothesized that eGFRcys is a feasible prognostic biomarker despite muscle sarcopenia in patients with PAD.

We calculated both eGFRcr and eGFRcys according to the Kidney Disease Improving Global Outcomes (KDIGO) guideline in 234 PAD patients who underwent endovascular therapy. Patients were prospectively followed during a median follow-up period of 964 days for the endpoint of major adverse cardiovascular and cerebrovascular events (MACCE). On multivariate Cox proportional hazard analysis eGFRcys, but not eGFRcr, was an independent predictor of MACCE. The C index was larger for eGFRcys than eGFRcr (0.69 vs. 0.
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