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No abstract is provided for this article.

No abstract is provided for this article.

Increased major adverse cardiac events (MACE) beyond six months after intracoronary β radiation brachytherapy (IRBT) are a major concern. The aim of this study was to evaluate the 10-year clinical outcome after IRBT.From 1997 to 2002, 301 consecutive patients treated with IRBT were included prospectively, whereafter 602 control patients treated with conventional percutaneous coronary intervention (PCI) were matched by propensity score methodology. MACE was defined as all-cause death, any myocardial infarction or any revascularisation. Median follow-up duration was 9.7 years. Mortality rates in both groups were similar. Cumulative 5-month, 2-, and 10- year MACE-free survival rates of IRBT patients were 89%, 56% and 29%, respectively, while those of the control patients were 90%, 76% and 52%, respectively (p < 0.001). The difference in the MACE rate was mainly driven by target vessel revascularisation (TVR) (p < 0.001). Furthermore, two or more repeat TVRs were needed in 12% of IRBT patients and in only 6% of control patients (p < 0.01). Adjusted hazard ratios for IRBT-associated all-cause mortality and MACE were 1.0 (95% CI 0.7-1.5) and 1.8 (95% CI 1.5-2.2), respectively.IRBT was associated with increased MACE between five months and two years of follow-up, mainly driven by repeat revascularisations. Similar event rate after two years indicate that there were no very late adverse effects related to IRBT.

The feasibility of assessing arterial wall characteristics with an intravascular 40 MHz ultrasonic imaging device was determined in vitro. Ten autopsy specimens of human arteries, with and without atherosclerosis, were studied. A close relationship was observed between the histologic section and the corresponding ultrasonic cross-section with regard to the location, maximum plaque thickness and extent of the atherosclerotic lesion along the circumference of the vessel wall. Based on echogenicity of the atherosclerotic lesion, ultrasound could distinguish four basic types of atherosclerotic plaque components: 1. hypoechoic: a reflection of lipid deposits; 2. soft echoes: reflective of fibromuscular tissue; 3. bright echoes: representative of fibrous tissue; 4. bright echoes with shadowing behind the lesion: representative of calcium deposits. It is anticipated that development of such a catheter-tip imaging system combined with recanalisation methods will be of immense benefit for the precise localisation and identification of vessel wall pathology, precise positioning of a recanalisation instrument (laser device, atherectomy catheter) and subsequent use of this recanalisation procedure and for assessing the effect of recanalisation.

Ozone is an oxidizing environmental pollutant that contributes significantly to respiratory health. Exposure to increased levels of ozone has been associated with worsening of symptoms of patients with asthma and COPD (chronic obstructive pulmonary disease). In the present study, we investigated the acute and chronic effects of ozone exposure-induced oxidative stress-related inflammation mechanics in mouse lung. In particular, we investigated the oxidative stress-induced effects on HDAC2 (histone deacetylase 2) modification and activation of the Nrf2 (nuclear factor erythroid-related factor 2) and HIF-1α (hypoxia-inducible factor-1α) signalling pathways. Male C57BL/6 mice were exposed to ozone (3 p.p.m.) for 3 h a day, twice a week for a period of 1, 3 or 6 weeks. Control mice were exposed to normal air. After the last exposure, mice were killed for BAL (bronchoalveolar lavage) fluid and lung tissue collection. BAL total cell counts were elevated at all of the time points studied. This was associated with increased levels of chemokines and cytokines in all ozone-exposed groups, indicating the presence of a persistent inflammatory environment in the lung. Increased inflammation and Lm (mean linear intercept) scores were observed in chronic exposed mice, indicating emphysematous changes were present in lungs of chronic exposed mice. The antioxidative stress response was active (indicated by increased Nrf2 activity and protein) after 1 week of ozone exposure, but this ability was lost after 3 and 6 weeks of ozone exposure. The transcription factor HIF-1α was elevated in 3- and 6-week ozone-exposed mice and this was associated with increased gene expression levels of several HIF-1α target genes including Hdac2 (histone deacetylase 2), Vegf (vascular endothelial growth factor), Keap1 (kelch-like ECH-associated protein 1) and Mif (macrophage migration inhibitory factor). HDAC2 protein was found to be phosphorylated and carbonylated in nuclear and cytoplasm fractions, respectively, and was associated with a decrease in DNA-binding activity and protein expression of HDAC2. Decreased HDAC2 activity, most likely a direct result of protein modification, in combination with the loss of the antioxidative stress response and activation of the HIF-1α pathway, contribute to the inflammatory response and emphysema observed in ozone-exposed mice.

No abstract is provided for this article.

Bipyridine derivatives have recently been introduced as a new class of inodilator drugs in the intravenous therapy of heart failure. A member of this class is milrinone, which improves the inotropic state and reduces ventricular afterload, leading to improved hemodynamics. Because systolic and diastolic function are intimately related, it can be expected that the diastolic muscle properties are influenced by changes in systolic function and therefore by milrinone therapy. Since end-diastolic pressure may shift as a result of a change in ventricular volume alone, a complete left ventricular diastolic pressure volume (LVDPV) relationship must always be measured before one can make firm conclusions regarding changes in diastolic function. After a LVDPV relationship is obtained, one should identify the variables that can modify this relationship without directly affecting the intrinsic diastolic muscle properties. These variables can be divided into static effects (coronary vascular bed volume, right ventricular pressure, and pericardial pressure) and dynamic effects (viscoelasticity and myocardial active relaxation). Increments in coronary perfusion pressure of perfusion flow (vascular bed volume) are known to stiffen the cardiac wall (turgor effect). Changes in right ventricular pressure or pericardial pressure are other factors affecting the LVDPV relationship by changing transmural pressure. This effect is more pronounced when the ventricle is already stiff, such as in patients with myocardial hypertrophy. Dynamic effects become important when a LVDPV relationship is measured during isolated cardiac cycles; they include viscoelasticity and abnormal myocardial relaxatlon. Clinical assessment of diastolic cardiac performance assumes a model in which the heart is considered an elastic body (while in fact it is viscoelastic). Therefore any increment in filling rate (dv/dt) will decrease the distensibility and result in a higher end-diastolic pressure. Abnormal relaxation is consistently present in patients with heart failure. It increases early diastolic myocardial stiffness caused by longer muscle activation (passive), and thus the LVDPV relationship will shift upward. In view of these considerations, how does one interpret the effects of milrinone on diastolic performance? The improved contractility increases cardiac metabolism and coronary blood flow. As a result, the cardiac wall stiffens by the erectile effect. An increase in atrial contractility must also be considered. This will increase the filling rate and will stiffen the wall further because of a viscoelastic effect in late diastole. The relaxation rate is affected by changes in afterload (vasodilation) and level of contractility. Both of these effects tend to increase the relaxation rate and distensibility of the left ventricle measured from the LVDPV relationship. This change in relaxation rate is independent of the direct changes in muscle properties. The erectile and viscoelastic effects counteract active relaxation, reflecting a direct milrinone effect. These effects probably explain why in our study there was an increase in distensibility in some patients and a decrease in distensibility in others after milrinone therapy. In view of the problems in controlling the variables in humans affecting the LVDPV relationship, the present results make it difficult to draw firm conclusions regarding the effect of milrinone on cardiac performance.

COPD (chronic obstructive pulmonary disease) is associated with sustained inflammation, excessive injury, and accelerated lung aging. Human Klotho (KL) is an anti-aging protein that protects cells against inflammation and damage. In the present study, we quantified KL expression in the lungs of COPD patients and in an ozone-induced mouse model of COPD, and investigated the mechanisms that control KL expression and function in the airways. KL distribution and levels in human and mouse airways were measured by immunohistochemistry and Western blotting. The effect of CSE (cigarette smoke extract) on KL expression was detected in human bronchial epithelial cells. Moreover, the effect of KL on CSE-mediated inflammation and hydrogen peroxide-induced cellular injury/apoptosis was determined using siRNAs. KL expression was decreased in the lungs of smokers and further reduced in patients with COPD. Similarly, 6 weeks of exposure to ozone decreased KL levels in airway epithelial cells. CSE and TNFα (tumour necrosis factor α) decreased KL expression and release from airway epithelial cells, which was associated with enhanced pro-inflammatory cytokine expression. Moreover, KL depletion increased cell sensitivity to cigarette smoke-induced inflammation and oxidative stress-induced cell damage. These effects involved the NF-κB (nuclear factor κB), MAPK (mitogen-activated protein kinase) and Nrf2 (nuclear factor erythroid 2-related factor 2) pathways. Reduced KL expression in COPD airway epithelial cells was associated with increased oxidative stress, inflammation and apoptosis. These data provide new insights into the mechanisms associated with the accelerated lung aging in COPD development.

<b>Background:</b> COPD is a chronic lung inflammatory disease linked to lung aging and cellular senescence. MicroRNAs (miRNA) are 21-23 non-coding RNAs that induce post-transcriptional repression of their mRNA targets. Extracellular vesicles (EVs) carry miRNA, mRNA and proteins and play a key role in intercellular communication. Dysregulation of miRNA expression in cells and in EVs may participate in the induction and spreading of cellular senescence in COPD <b>Aim:</b> To compare miRNAs species encapsulated in EVs produced by small airway epithelial cells from healthy and COPD donors and their role on epithelial cells senescence <b>Methods:</b> Small airway epithelial cells (SAEC) from healthy donors and COPD patients were plated in submerged culture and EVs were isolated by differential ultracentrifugation of cell supernatants. Total RNAs from cells and EVs were isolated and miRNA species were analysed by miRNA sequencing <b>Results:</b> 13 miRNAs were significantly upregulated in EVs derived from COPD SAEC compared to healthy subjects (n=5). All miRNAs were also found upregulated in COPD SAEC compared to healthy subjects. Six miRNAs were implicated in senescence pathways: miR-100-5p (1.38 fold increase in COPD EVs), miR-424-5p (3.18-fold increase), miR-19b-3p (1.95-fold increase), miR-20a-5p (0.58-fold increase), miR-27a-3p (1.08-fold increase), miR-17-5p (0.68-fold increase) <b>Conclusion:</b> Our data suggest that EVs derived from COPD SAEC are enriched in miRNA involved in cellular senescence. This may contribute to COPD pathophysiology by inducing cellular senescence in adjacent cells. Further exploration of vesicular miRNAs in COPD may provide useful biomarkers and targets for therapy.

When a lesion is unstable, it may rupture and cause an acute thrombotic reaction. A rupture prone plaque contains a large lipid pool covered by a thin fibrous cap. Intravascular ultrasound (IVUS) elastography can assess the presence of lipid pools and identify high stress regions. The deformation of the tissue is determined using ultrasound. For intravascular purposes, the intraluminal pressure is used as the excitation force. The radial strain in the tissue is obtained by cross-correlation techniques on the radio frequency (rf) signal. The strain is colour-coded and plotted as a complimentary image to the IVUS echogram , or , in case of palpography, as a ring on the lumen vessel boundary.

No abstract is provided for this article.

Background and purpose Intracoronary brachytherapy after percutaneous transluminal coronary angioplasty (PTCA) is usually performed with catheter-based treatment techniques in a straight vessel segment. There is a growing interest for treatment of bifurcations, which requires consecutive positioning of the source in main vessel and side branch. Materials and methods In-house developed software (IC-BT doseplan) is used to explore the optimal positioning of the source in modelled bifurcations with different shape for the source types available in our hospital, i.e. 90Sr/90Y, 32P and 192Ir. The results were summarised in look-up tables. The usefulness of these look-up tables was tested on various clinical examples. Results Tabulated results for the modelled bifurcations yield an estimation of the distance between the sources (gap width) in relation to the geometry and source type: 90Sr/90Y gap range 3–8.5 mm, 32P gap range 2–7 mm and 192Ir gap range 3.5–8 mm. The average dose relative to 2 mm from the source axis is: 90Sr/90Y, (mean±SD) 120±40%; 32P, 125±50% and 192Ir, 120±22%. The look-up tables also provide the coarse location and value of maximum and minimum dose: 90Sr/90Y, 220–60%, 32P, 230–55% and 192Ir, 170–85%. It appeared that the look-up tables provide a good approximation of the optimal gap width in the clinical examples. Conclusions Tabulated optimal gap widths are very useful for quick estimation of the required gap width for a given bifurcation and source type, in case the prescribed dose in both vessels is the same. In unfavourable geometries there is a risk of local underdosage. Individual treatment planning using a program such as IC-BT doseplan is then recommended.