Publications

No abstract is provided for this article.

Objectives The aim of this study was to compare long-term survival between patients with severe coronary artery disease undergoing coronary artery bypass grafting (CABG) and those undergoing percutaneous coronary intervention (PCI) achieving complete revascularization (CR) or incomplete revascularization. Background The importance of CR in decision making regarding revascularization strategy in patients with severe coronary artery disease is unknown. Methods Data were pooled from the SYNTAX (Synergy Between PCI With Taxus and Cardiac Surgery), PRECOMBAT (Premier of Randomized Comparison of Bypass Surgery Versus Angioplasty Using Sirolimus-Eluting Stent in Patients With Left Main Coronary Artery Disease), and BEST (Randomized Comparison of Coronary Artery Bypass Surgery and Everolimus-Eluting Stent Implantation in the Treatment of Patients With Multivessel Coronary Artery Disease) trials. The primary outcome was death from any cause and was compared in an as-treated analysis. Results The rate of CR was 61.7% (57.2% with PCI and 66.8% with CABG). During a median 4.9-year follow-up period (interquartile range: 4.5 to 5.0 years), compared with patients undergoing CABG with CR, those undergoing PCI with incomplete revascularization had a higher risk for death from any cause (adjusted hazard ratio [aHR]: 1.43; 95% confidence interval [CI]: 1.03 to 2.00; p = 0.036) and the composite of death, myocardial infarction, and stroke (aHR: 1.48; 95% CI: 1.14 to 1.92; p = 0.003). However, there was no significant difference between patients undergoing CABG with CR and those undergoing PCI with CR regarding the risk for death from any cause (aHR: 1.16; 95% CI: 0.83 to 1.63; p = 0.39) and the composite of death, myocardial infarction, and stroke (aHR: 1.14; 95% CI: 0.87 to 1.48; p = 0.35). Subgroup analysis of multivessel coronary disease, high SYNTAX score (>32), and diabetes showed consistent findings. Conclusions For the treatment of left main or multivessel coronary artery disease, PCI resulting in CR was associated with a similar long-term survival rate to CABG resulting in CR. Therefore, the ability to achieve CR should enter into the decision algorithm for choice of revascularization strategy.

Glucocorticoids have an inhibitory effect on inflammatory and immune responses, and this may be through the modulation of transcription factor binding to DNA. The interaction of the transcription factors, activator protein-1 (AP-1), nuclear factor kappa B (NF kappa B), and cAMP-responsive element binding protein (CREB) with DNA and glucocorticoid receptors (GR) was analyzed in human peripheral blood mononuclear cells by gel mobility shift assays. TNF-alpha, IL-1 beta and phorbol myristate acetate (PMA) treatment increased AP-1 and NF kappa B DNA binding by up to 200% but decreased CREB binding (38%) over a 60-min time course. Dexamethasone produced a rapid and sustained increase in glucocorticoid response element binding and a concomitant 40-50% decrease in AP-1, NF kappa B, and CREB DNA binding that was blocked by combined dexamethasone and cytokine or PMA treatment. These latter effects were due to increases in the nuclear localization of GR, not to reduced amounts of the other transcription factors. This suggests that in these cells GR within the nucleus interacts with cytokine-stimulated transcription factors by the process of cross coupling. This may be an important molecular site of steroid action.

We have recently completed an observing program with the Australia Telescope Compact Array towards massive star formation regions traced by 6.7 GHz methanol maser emission. We found the molecular cores could be separated into groups based on their association with/without methanol maser and 24 GHz continuum emission. Analysis of the molecular and ionised gas properties suggested the cores within the groups may be at different evolutionary stages. In this contribution we derive the column densities and temperatures of the cores from the NH3 emission and investigate if this can be used as an indicator of the relative evolutionary stages of cores in the sample. The majority of cores are well fit using single-temperature large velocity gradient models, and exhibit a range of temperatures from ~10 K to >200 K. Under the simple but reasonable assumption that molecular gas in the cores will heat up and become less quiescent with age due to feedback from the powering source(s), the molecular gas kinetic temperature combined with information of the core kinematics seems a promising probe of relative core age in the earliest evolutionary stages of massive star formation.

No abstract is provided for this article.

Background The SYNTAX Extended Survival (SYNTAXES) study is an investigator-driven extension of follow-up of the SYNTAX trial, which was a non-inferiority trial that compared percutaneous coronary intervention (PCI) using first-generation paclitaxel-eluting stents with coronary artery bypass grafting (CABG) in patients with de-novo three-vessel and left main coronary artery disease. The SYNTAXES study is the first randomized trial that reported the complete 10-year data on all-cause death in patients with complex coronary artery disease. Purpose Patients with coronary artery disease (CAD) and concomitant diabetes mellitus (DM) or chronic kidney disease (CKD) are more susceptible to major adverse cardiovascular and cerebrovascular events. However, to date, the long-term prognosis and which revascularization strategy was associated with better clinical outcomes for patients with complex coronary artery disease and concomitant with DM and CKD have not been documented. Methods In this sub-analysis of the SYNTAXES trial, a total of 1,638 patients were classified into four subgroups according to the DM and CKD status: DM−/CKD− (n=999, 60.1%), DM+/CKD− (n=323, 19.7%), DM−/CKD+ (n=231, 14.1%), and DM+/CKD+ (n=85, 5.2%). The treatment effects of PCI and CABG were analyzed in each subgroup. The primary endpoint was all-cause death at 10 years. Results Compared with the DM−/CKD− patients, patients with DM+/CKD+ were older, more often had a history of stroke, hypertension, heart failure, and were more frequently presented with total occlusion, bifurcation lesion and three-vessel disease. At 10 years, patients with DM+/CKD+ had a 3.94-fold higher incidence of all-cause mortality compared with DM−/CKD− individuals (54.1% versus 18.9%, 95% CI [2.85–5.44]). Patients with DM−/CKD+ (38.1%, HR 2.36; 95% CI [1.83–5.44]) or DM+/CKD− (28.2%, HR 1.61; 95% CI [1.26–2.07]) had intermediate risk profile. For DM+/CKD+ patients, compared with PCI, those who underwent CABG were associated with lower incidence of all-cause mortality (64.3% versus 44.2%, adjusted HR 0.52; 95% CI [0.27–0.99], p=0.047, pinteraction=0.443). The number of needed-to-treat to reduce mortality for CABG was 12. Conclusion In the SYNTAX population, patients with DM and CKD are at markedly increased risk of long-term mortality rate compared with patients one or neither of these risk factors. For patients with both comorbidities, CABG was associated with better clinical outcome compared with PCI. These findings should be interpreted as hypothesis-generating. Figure 1. Kaplan-Meier curves showing the clinical events according to treatment and DM/CKD status. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Boston Scientific Corporation

Pulmonary macrophages are a target for inhaled therapies. Combinations of long-acting β 2 -agonists (LABA) and glucocorticosteroids have been developed for asthma and chronic obstructive pulmonary disease (COPD). This study examined two LABA, salmeterol and formoterol, and the glucocorticosteroid, budesonide, on cytokine release from monocyte-derived macrophages (MDM) to determine whether anti-inflammatory effects observed in patients are due to inhibition of macrophages. MDM were incubated in the absence or presence of LABA or budesonide prior to stimulation with lipopolysaccharide (LPS). Tumour necrosis factor (TNF)-α, granulocyte macrophage-colony stimulating factor (GM-CSF) and CXC chemokine ligand (CXCL)8 were measured by ELISA. Formoterol and salmeterol inhibited LPS-stimulated release of TNF-α (mean effective concentration (EC 50 ) 2.4±1.8 and 3.5±2.7 nM, respectively; n = 11–16), GM-CSF (EC 50 24.6±2.1 and 52.4±40.8 nM, respectively, n = 11–12) but not CXCL8 from LPS-stimulated MDM. Budesonide inhibited release of all three cytokines (EC 50 TNF-α: 1.2±0.4 nM; GM-CSF: 0.4±0.2 nM; CXCL8: 0.4±0.1 nM; n = 3–4). Formoterol but not salmeterol elevated cAMP in these cells. These effects were attenuated by β-adrenoceptor antagonists, propranolol and ICI118551. Salmeterol (10 −7 M) also inhibited formoterol-induced cAMP and formoterol-mediated attenuation of cytokine release. Combining budesonide (0.3 nM) with formoterol, inhibited TNF-α release additively. LABA may inhibit inflammatory cytokine release from macrophages in a cAMP-independent manner and act additively with budesonide.

The average low shear stress (SS) is known to determine predilection sites of atherosclerotic plaques. However, as plaques encroach into the lumen and thereby increase SS, interpretation of patient-specific data obtained at one moment in time regarding the influence of SS in the generation of atherosclerosis is not straightforward. This study aims to compare two methods of data analysis for the aid of data interpretation: (a) point-wise analysis of the raw data, (b) global analysis: to assess the history related natural SS distribution in coronary arteries by averaging the data in the axial vessel direction. Normal to mildly diseased human coronary arteries were investigated applying a combination of 3-D reconstruction technique and computational fluid dynamics (CFD). Point-wise analysis relating local wall thickness to local SS showed in only 4% of the cases an inverse relationship. In contrast, averaging the data in the axial vessel direction, showed in 38% a significant inverse relation between wall thickness and SS, resulting in an average negative slope of −0.70±0.46mm/Pa. These data suggest that using a geometry guided way of data averaging may reveal history related effects of SS, which in part explains localization of atherosclerotic plaques.

No abstract is provided for this article.

Because of their ability to perfuse remote regions and deliver oxygen, hemoglobin-based oxygen carriers (HBOCs) may be considered in the treatment of several ischemic conditions such as acute coronary syndromes or high-risk percutaneous intervention. Here we studied the effects of intracoronary infusion of ex vivo preoxygenated HBOC-201 during brief total coronary artery occlusion (CAOs) on myocardial oxygenation and left ventricular (LV) function in a large animal model and investigated the influence of HBOC-201 temperature and infusion rate on these effects. Thirteen open-chest anesthetized swine were instrumented for measurement of global and regional LV function and metabolism. CAOs were induced by inflating an intracoronary balloon catheter; preoxygenated HBOC-201 (12 g/dL) was infused distally through the central lumen of the balloon catheter. Animals underwent consecutive 3-min CAOs interspersed by 30 min of reperfusion, accompanied by different HBOC-201 infusion rates (0, 15, 23, 30, 40, and 50 ml/min) and/or two infusion temperatures (18 degrees C or 37 degrees C) in random order. CAO elicited immediate loss of systolic shortening (SS) in the ischemic region (19 +/- 1% at baseline vs. -3 +/- 2% at end of CAO), resulting in decreases in maximum rate of rise in LV pressure (15 +/- 5%) and stroke volume (12 +/- 4%; all P < 0.05). Balloon deflation resulted in marked coronary reactive hyperemia (to 472 +/- 74% of baseline), increases in coronary venous concentrations of adenosine + inosine (to 218 +/- 26% of baseline; both P < 0.05) and rapid restoration of SS toward baseline. HBOC-201 ameliorated the CAO-induced changes in SS, stroke volume, reactive hyperemia, and coronary venous adenosine + inosine. The effects were temperature and flow dependent with full preservation of SS at 50 ml/min HBOC-201 of 37 degrees C. In conclusion, intracoronary preoxygenated HBOC-201 preserved myocardial oxygenation and LV function in swine during CAO in a dose- and temperature-dependent manner. In our study setting, preoxygenated HBOC-201 can match the oxygen delivery role of endogenous blood in the heart on an almost equivalent-volume basis.