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There is a paucity of data on the effect of baseline lipid-lowering therapy (LLT) in patients undergoing revascularization for left main (LM) coronary artery disease (CAD). We compared outcomes for patients with LMCAD randomized to percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) according to the presence of baseline LLT in the EXCEL trial.The EXCEL trial randomized 1905 patients with LMCAD and SYNTAX scores up to 32 to PCI with everolimus-eluting stents versus CABG. Patients were categorized according to whether they were medically treated with LLT at baseline, and their outcomes were examined using multivariable Cox proportional hazards regression. The primary endpoint was a composite of death, stroke, or myocardial infarction at 3 years.Among 1901 patients with known baseline LLT status, 1331 (70.0%) were medically treated with LLT at baseline. There were no significant differences between the PCI and CABG groups in the 3-year rates of the primary endpoint in patients with versus without baseline LLT (Pinteraction=0.62). Among patients with baseline LLT, the 3-year rate of ischemia-driven revascularization was higher after PCI compared with CABG (13.7 vs. 5.3%; adjusted hazard ratio=2.97; 95% confidence interval: 1.95-4.55; P<0.0001), in contrast to patients without baseline LLT (9.8 vs. 12.1%; adjusted hazard ratio=0.79; 95% confidence interval: 0.47-1.33; P=0.39) (Pinteraction=0.0003).In the EXCEL trial, 3-year major adverse event rates after PCI versus CABG for LMCAD were similar and consistent in patients with and without LLT at baseline; however, revascularization during follow-up was more common after PCI compared with CABG in patients with baseline LLT, but not in those without baseline LLT.

Long-length stenting has a poor outcome when bare metal stents are used. The safety and efficacy of the sirolimus-eluting stent (SES) in long lesions has not been evaluated. Therefore, the aim of the present study was to evaluate the clinical and angiographic outcomes of SES implantation over a very long coronary artery segment. Since April 2002, all patients treated percutaneously at our institution received a SES as the device of choice as part of the Rapamycin Eluting Stent Evaluated At Rotterdam Cardiology Hospital (RESEARCH) registry. During the RESEARCH registry, stents were available in lengths of 8, 18, and 33 mm. The present report includes a predefined study population consisting of patients treated with >36-mm-long stented segments. Patients had a combination of ≥2 overlapping stents at a minimum length of 41 mm (i.e., one 33-mm SES overlapping an 8-mm SES) to treat native de novo coronary lesions. The incidence of major cardiac adverse events (death, nonfatal myocardial infarction, and target lesion revascularization) was evaluated. The study group comprised 96 consecutive patients (102 lesions). Clinical follow-up was available for all patients at a mean of 320 days (range 265 to 442). In all, 20% of long-stented lesions were chronic total occlusions, and mean stented length per lesion was 61.2 ± 21.4 mm (range 41 to 134). Angiographic follow-up at 6 months was obtained in 67 patients (71%). Binary restenosis rate was 11.9% and in-stent late loss was 0.13 ± 0.47 mm. At long-term follow-up (mean 320 days), there were 2 deaths (2.1%), and the overall incidence of major cardiac events was 8.3%. Thus, SES implantation appears safe and effective for de novo coronary lesions requiring multiple stent placement over a very long vessel segment.

Objectives In the absence of effective clinical pharmacotherapy for prevention of reperfusion-mediated injury, this study re-evaluated the effects of intracoronary adenosine on infarct size and no-reflow in a porcine model of acute myocardial infarction using clinical bolus and experimental high-dose infusion regimens. Background Despite the clear cardioprotective effects of adenosine, when administered prior to ischemia, studies on cardioprotection by adenosine when administered at reperfusion have yielded contradictory results in both pre-clinical and clinical settings. Methods Swine (54 ± 1 kg) were subjected to a 45-min mid–left anterior descending artery occlusion followed by 2 h of reperfusion. In protocol A, an intracoronary bolus of 3 mg adenosine injected over 1 min (n = 5) or saline (n = 10) was administered at reperfusion. In protocol B, an intracoronary infusion of 50 μg/kg/min adenosine (n = 15) or saline (n = 21) was administered starting 5 min prior to reperfusion and continued throughout the 2-h reperfusion period. Results In protocol A, area-at-risk, infarct size, and no-reflow were similar between groups. In protocol B, risk zones were similar, but administration of adenosine resulted in significant reductions in infarct size from 59 ± 3% of the area-at-risk in control swine to 46 ± 4% (p = 0.02), and no-reflow from 49 ± 6% of the infarct area to 26 ± 6% (p = 0.03). Conclusions During reperfusion, intracoronary adenosine can limit infarct size and no-reflow in a porcine model of acute myocardial infarction. However, protection was only observed when adenosine was administered via prolonged high-dose infusion, and not via short-acting bolus injection. These findings warrant reconsideration of adenosine as an adjuvant therapy during early reperfusion.

Background Although prosthetic conduits for coronary artery bypass grafting (CABG) are increasingly needed because of the limited availability and patency of autologous conduits, no alternatives have succeeded. Methods Sixteen sheep underwent CABG. Thirteen received a bioabsorbable polymer graft with an incorporated nitinol microskeleton (Xeltis coronary artery bypass graft [XABG]), and three received autologous saphenous vein grafts (SVG). Pathological evaluation was conducted at 12 months. Results In the XABG group, two sheep died perioperatively; two were sacrificed at 3 months (1 occluded, 1 patent) and two at 6 months (both patent). Two more died from occlusion at 9–10 months, and five survived with patent grafts at 12 months. All SVGs remained patent for 12 months. Histology demonstrated near-complete luminal endothelialization in XABG, with increased polymer adsorption and matrix deposition. The cross-sectional area of the SVG lumen was significantly larger than XABGs (48.2 mm 2 vs 12.9 mm 2 , p = 0.0018), consistent with a reduced angiographic flow velocity in SVG. The neointimal area was greater in SVGs than XABGs (19.6 vs. 6.7 mm 2 , p = 0.0005), especially at the distal ends of SVGs due to thrombus formation. Conclusion XABG demonstrated 1-year feasibility with consistent endothelialization and polymer absorption. While SVGs had better patency, they showed greater diametrical irregularity and subsequent neointimal proliferation.

Our aim was to evaluate the long-term device performance and clinical outcomes of patients with symptomatic, severe aortic valve stenosis (AS) who underwent transcatheter aortic valve implantation (TAVI) with the CoreValve bioprosthesis.The CoreValve CE Pivotal Study was a prospective, multicentre, single-arm TAVI trial using the CoreValve system. Valve performance, patient quality of life (QoL), New York Heart Association (NYHA) class, and mortality at four years were analysed in 126 patients (mean age 82.4 years, 42.9% male, mean logistic EuroSCORE 23.4%) with severe AS. Mean aortic valve gradient decreased from 46.9±16.1 mmHg at baseline to 9.8±4.1 mmHg at discharge and to 7.8±2.7 mmHg at four years. Mean effective orifice area increased from 0.7±0.2 cm2 to 1.8±0.4 cm2 after TAVI and was 1.6±0.5 cm2 at four years. There were no reports of structural valve deterioration or valve migration. There was sustained improvement in QoL and NYHA class in surviving patients. All-cause and cardiac survival was 45.3% and 62.6%, respectively, at four years.The CoreValve bioprosthesis demonstrates long-term durability, stable haemodynamic function, and no evidence of structural deterioration. Most surviving patients continued to have improved NYHA class and QoL at four years.

No abstract is provided for this article.

In the setting of ST-elevation myocardial infarction (STEMI), epicardial vasoconstriction and thrombus load may lead to stent undersizing and malapposition after primary percutaneous coronary intervention (PPCI), which can both be responsible for stent thrombosis or restenosis. Aggressive stent deployment can, on the other hand, cause distal embolisation and the no-reflow phenomenon. The purpose of our study was to evaluate the safety and feasibility of a novel self-expanding stent by assessing the clinical, angiographic and intravascular outcomes after stent deployment at three days and at six months follow-up.This prospective, multicentre, non-randomised study enrolled 25 STEMI patients undergoing PPCI; a nitinol, self-expanding, coronary stent (STENTYS® stent; STENTYS, Paris, France) was used in all patients. Angiography and intravascular ultrasound (IVUS) or optical coherence tomography (OCT) were performed immediately after stent deployment, after three days and at six months. Primary safety endpoints were mortality, reinfarction, stent thrombosis and stroke at discharge and at six months. The primary feasibility endpoints were technical, device and procedural success, and stent apposition at three days and six months. Secondary endpoints included distal embolisation, binary restenosis, ischaemia-driven target lesion revascularisation (TLR) and late lumen loss (LLL). There were no adverse events at discharge or at six months. Technical, device and procedural success were 100%, 96% and 96%, respectively. IVUS showed a significant vasodilatation distal to the culprit lesion at three-day follow-up (+19%), with a concordant expansion of the implanted stent (+18%), p≤0.001 for both values. One case of distal embolisation was reported. There were no cases of late stent malapposition at six months. In-stent and in-segment LLL were 0.71±0.71 mm and 0.58±0.61 mm. Binary restenosis was 25%, ischaemia-driven TLR was 12%.This study shows that the use of the STENTYS® self-expanding stent is safe and feasible in STEMI patients. Three days after the procedure, the stent expanded to the same extent as the epicardial vasodilatation and appeared completely apposed to the vessel wall. This could be of benefit in preventing stent thrombosis in the setting of STEMI.

The localization and distribution of the human glucocorticoid receptor (GR) mRNA and protein was investigated in human lung obtained from transplant donors and recipients by in situ hybridization, RNA blot analysis, immunolocalization, and Western analysis. Subjects were either nonasthmatic or had mild asthma requiring only beta(2)-agonists. No difference in amount of GR mRNA was found in total RNA isolated from nonasthmatic or asthmatic donor lung. In situ hybridization showed the highest concentration of GR mRNA in the alveolar walls and vascular endothelium and smooth muscle, with lesser amounts in the airway epithelium and smooth muscle. There was no change in the level or sites of expression of GR mRNA between normal and asthmatic subjects. Immunolocalization of GR confirmed the in situ hybridization data. There was no change in the level or sites of expression of GR, in either the lung or airway, between normal and asthmatic subjects. Immunolocalization of GR in bronchial biopsies from two normal and asthmatic subjects confirmed the localization and distribution of GR. Western analysis and mobility shift assays confirmed no differences in GR levels between the two subject groups. The localization of GR mRNA and protein to specific cell types within lung and airway will make it possible to study the cellular targets of glucocorticoid therapy in inflammatory lung diseases such as asthma.

Conference Abstract| January 01 1987 Oxygen and Theophylline Reduce the Cardiorespiratory Effects of Adenosine Infusion in Han D.L. Maxwell; D.L. Maxwell 1Depts. of Medicine, the Cardiothoracic Institute, London Search for other works by this author on: This Site PubMed Google Scholar R.W. Fuller; R.W. Fuller *Dept of Clinical Pharmacology, R.P.M.S., the Cardiothoracic Institute, London Search for other works by this author on: This Site PubMed Google Scholar T.B. Conradson; T.B. Conradson +Dept. of Clinical Pharmacology, the Cardiothoracic Institute, London Search for other works by this author on: This Site PubMed Google Scholar C.M.S. Dixon; C.M.S. Dixon +Dept. of Clinical Pharmacology, the Cardiothoracic Institute, London Search for other works by this author on: This Site PubMed Google Scholar J.M.B. Hughes; J.M.B. Hughes 1Depts. of Medicine, the Cardiothoracic Institute, London Search for other works by this author on: This Site PubMed Google Scholar P.J. Barnes P.J. Barnes +Dept. of Clinical Pharmacology, the Cardiothoracic Institute, London Search for other works by this author on: This Site PubMed Google Scholar Clin Sci (Lond) (1987) 72 (s16): 13P. https://doi.org/10.1042/cs072013P Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Twitter LinkedIn Cite Icon Cite Get Permissions Citation D.L. Maxwell, R.W. Fuller, T.B. Conradson, C.M.S. Dixon, J.M.B. Hughes, P.J. Barnes; Oxygen and Theophylline Reduce the Cardiorespiratory Effects of Adenosine Infusion in Han. Clin Sci (Lond) 1 January 1987; 72 (s16): 13P. doi: https://doi.org/10.1042/cs072013P Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsClinical Science Search Advanced Search This content is only available as a PDF. © 1987 The Biochemical Society and the Medical Research Society1987 Article PDF first page preview Close Modal You do not currently have access to this content.

No abstract is provided for this article.

BACKGROUND Coronary flow reserve (CFR), the functional index of stenosis severity more frequently used in the catheterization laboratory, is greatly affected by the hemodynamic conditions at the time of measurement and cannot be applied in the immediate assessment of the outcome of coronary interventions. The aim of the present study was to establish the feasibility and reproducibility of the assessment of the slope of the instantaneous diastolic relation between coronary flow velocity and aortic pressure during maximal hyperemia (IHDVPS) using a spectral analysis of the intracoronary Doppler signal, to assess the sensitivity and specificity of this index in the detection of flow-limiting coronary stenoses in comparison with CFR, and to study the possibility of determining the zero-flow pressure from the intercept of the velocity-pressure relation on the pressure axis during a controlled cardiac arrest. METHODS AND RESULTS The instantaneous peak coronary flow velocity measured after intracoronary papaverine with a Doppler guidewire was plotted against the simultaneously measured aortic pressure, and the slope of the velocity-pressure relation in the phase of progressive diastolic velocity decrease was calculated during four consecutive beats. In nine normal arteries, a controlled diastolic cardiac arrest was induced by an intracoronary bolus injection of 3 mg adenosine. The IHDVPS could be assessed in 79 of 95 patients (83%), with a moderate intraobserver variability (0.4 +/- 11% after independent selection of different beats during maximal hyperemia). The IHDVPS showed no significant correlation with heart rate, mean diastolic aortic pressure, type of vessel studied, and cross-sectional area at the site of the velocity recording. The IHDVPS was significantly lower in arteries with &gt; or = 30% diameter stenosis than in normal or near-normal arteries (0.71 +/- 0.48 versus 1.73 +/- 0.80 cm.s-1.mm Hg-1, P &lt; .0000002). In the stenosis group, both IHDVPS and CFR were significantly correlated with the minimal luminal cross-sectional area (r = .46, P &lt; .05 and r = .62, P &lt; .002, respectively). The study of the velocity-pressure relation during long diastolic pauses showed a curvilinear relation between velocity and pressure in the lower pressure range, with an upward concavity to the velocity axis and no intercept with the pressure axis in most cases. CONCLUSIONS The IHDVPS can distinguish between arteries with and without coronary stenoses and has a significant inverse correlation with the severity of the stenosis. Under the stable hemodynamic conditions of this study, the IHDVPS and CFR had similar sensitivities and specificities in distinguishing normal and stenotic vessels and demonstrated similar correlation with minimal luminal cross-sectional area. The curvilinearity of the velocity-pressure relation during long diastolic pauses, possibly due to a significant reduction of luminal cross-sectional area at low pressures, complicates the use of the flow velocity-pressure relation for the assessment of the zero-flow pressure.

Background CD8+ T-cells are located in the small airways of COPD patients and may contribute to pathophysiology. CD8+ cells express the chemokine receptor, CXCR3 that binds CXCL9, CXCL10 and CXCL11, which are elevated in the airways of COPD patients. These chemokines are released from airway epithelial cells via activation of receptor associated Janus kinases (JAK). This study compared the efficacy of two structurally dissimilar pan-JAK inhibitors, PF956980 and PF1367550, and the glucocorticosteroid dexamethasone, in BEAS-2B and human primary airway epithelial cells from COPD patients and control subjects. Methods Cells were stimulated with either IFNγ alone or with TNFα, and release of CXCL9, CXCL10 and CXCL11 measured by ELISA and expression of CXCL9, CXCL10 and CXCL11 by qPCR. Activation of JAK signalling was assessed by STAT1 phosphorylation and DNA binding. Results There were no differences in the levels of release of CXCL9, CXCL10 and CXCL11 from primary airway epithelial cells from any of the subjects or following stimulation with either IFNγ alone or with TNFα. Dexamethasone did not inhibit CXCR3 chemokine release from stimulated BEAS-2B or primary airway epithelial cells. However, both JAK inhibitors suppressed this response with PF1367550 being ~50-65-fold more potent than PF956980. The response of cells from COPD patients did not differ from controls with similar responses regardless of whether inhibitors were added prophylactically or concomitant with stimuli. These effects were mediated by JAK inhibition as both compounds suppressed STAT1 phosphorylation and DNA-binding of STAT1 and gene transcription. Conclusions These data suggest that the novel JAK inhibitor, PF1367550, is more potent than PF956980 and that JAK pathway inhibition in airway epithelium could provide an alternative anti-inflammatory approach for glucocorticosteroid-resistant diseases including COPD.