Objectives This study sought to describe the frequency and clinical impact of acute scaffold disruption and late strut discontinuity of the second-generation Absorb bioresorbable polymeric vascular scaffolds (Absorb BVS, Abbott Vascular, Santa Clara, California) in the ABSORB (A Clinical Evaluation of the Bioabsorbable Everolimus Eluting Coronary Stent System in the Treatment of Patients With De Novo Native Coronary Artery Lesions) cohort B study by optical coherence tomography (OCT) post-procedure and at 6, 12, 24, and 36 months. Background Fully bioresorbable scaffolds are a novel approach to treatment for coronary narrowing that provides transient vessel support with drug delivery capability without the long-term limitations of metallic drug-eluting stents. However, a potential drawback of the bioresorbable scaffold is the potential for disruption of the strut network when overexpanded. Conversely, the structural discontinuity of the polymeric struts at a late stage is a biologically programmed fate of the scaffold during the course of bioresorption. Methods The ABSORB cohort B trial is a multicenter single-arm trial assessing the safety and performance of the Absorb BVS in the treatment of 101 patients with de novo native coronary artery lesions. The current analysis included 51 patients with 143 OCT pullbacks who underwent OCT at baseline and follow-up. The presence of acute disruption or late discontinuities was diagnosed by the presence on OCT of stacked, overhung struts or isolated intraluminal struts disconnected from the expected circularity of the device. Results Of 51 patients with OCT imaging post-procedure, acute scaffold disruption was observed in 2 patients (3.9%), which could be related to overexpansion of the scaffold at the time of implantation. One patient had a target lesion revascularization that was presumably related to the disruption. Of 49 patients without acute disruption, late discontinuities were observed in 21 patients. There were no major adverse cardiac events associated with this finding except for 1 patient who had a non-ischemia-driven target lesion revascularization. Conclusions Acute scaffold disruption is a rare iatrogenic phenomenon that has been anecdotally associated with anginal symptoms, whereas late strut discontinuity is observed in approximately 40% of patients and could be viewed as a serendipitous OCT finding of a normal bioresorption process without clinical implications. (ABSORB Clinical Investigation, Cohort B [ABSORB B]; NCT00856856)
There is increasing evidence in many species that vasoactive intestinal peptide (VIP) may be a neurotransmitter in nonadrenergic inhibitory nerves. We have studied the effect of electrical field stimulation (EFS), exogenous VIP, and isoproterenol (Iso) on human airways in vitro. We have also studied a related peptide, peptide histidine methionine (PHM), which coexists with VIP in human airway nerves, and in separate experiments studied fragments of the VIP amino acid sequence (VIP1–10 and VIP16–28) for agonist and antagonist activity. Human airways were obtained at thoracotomy and studied in an organ bath. In bronchi EFS gave an inhibitory response that was unaltered by 10(-6) M propranolol but was blocked by tetrodotoxin, whereas in bronchioles there was little or no nonadrenergic inhibitory response. VIP, PHM, and Iso all caused dose-dependent relaxation of bronchi, VIP and PHM being approximately 50-fold more potent than Iso. VIP, but not Iso, mimicked the time course of nonadrenergic inhibitory nerve stimulation. In contrast bronchioles relaxed to Iso but not to VIP or PHM. Neither propranolol nor indomethacin altered the relaxant effects of VIP or PHM, suggesting a direct effect of these peptides on airway smooth muscle. Neither of the VIP fragments showed either agonist or antagonist activity. We conclude that VIP and PHM are more potent bronchodilators of human bronchi than Iso and that the association between the relaxant effects of these peptides and nonadrenergic inhibitory responses suggests that they may be possible neurotransmitters of nonadrenergic inhibitory nerves in human airways.
The hypothesis that endothelium-derived relaxing factor (EDRF) modulates hypoxic pulmonary vasoconstriction (HPV) was tested in isolated, blood-perfused rat lungs ventilated with gas mixtures of 21% O2-5% CO2-74% N2 (normoxia) or of 3% O2-5% CO2-92% N2 (hypoxia); 30 µM NG-monomethyl-l-arginine (l-NMMA), an inhibitor of EDRF production, caused a reduction in the endothelium-dependent relaxant response to acetylcholine (ACh) from 62 ± 7, 88 ± 4, and 100 ± 4% to 26 ± 8, 49 ± 12, and 75 ± 7% at ACh concentrations of 1, 10, and 100 µM, respectively (p < 0.05 at all concentrations), indicating that l-NMMA acts via the inhibition of EDRF production. l-NMMA induced a concentration-related augmentation in HPV of 20 ± 5, 32 ± 8, and 34 ± 8% at concentrations of 30, 300, and 1,000 µM (p < 0.05, compared with a vehicle control group at all concentrations). The pressor response to a dose of anglotensin II (A-II), which produced the same increase in pulmonary artery pressure as that induced by hypoxia, was also significantly augmented (2 ± 0.6%), but to a lesser extent. The augmentation of HPV by 30 µM l-NMMA was completely reversed by 1 mM l-arginine (a precursor of EDRF), but not by d-arginine (an isomer of l-arginine). One and 6 mM l-arginine, but not 6 mM d-arginine caused a significant inhibition of HPV by 20 ± 2 and 47 ± 12% (p< 0.05, compared with the vehicle control group) and a small but not significant reduction in A-II-mediated contraction. We conclude that endothelium-derived relaxing factor modulates HPV and that the modulating action of EDRF on pulmonary blood pressure may be more relevant to HPV than to A-II-induced contraction. The ability of l-arginine to reduce HPV suggests that the formation of EDRF during hypoxemia may be limited by the availability of its precursor.
Eicosanoids such as leukotrienes, prostaglandins, lipoxins, and 15-hydroperoxyeicosatetraenoic acid (15-HETE) cause bronchoconstriction, increased microvascular permeability, mucus secretion, and polymorph chemotaxis. These pro-inflammatory effects are important in diseases such as asthma and cystic fibrosis where the levels of mediators are increased both in the stable and acute state. A study was conducted to examine the expression of the mRNA for the enzymes of the eicosanoid pathways (5-lipoxygenase (5-LO), 5-lipoxygenase activating protein (FLAP), cyclo-oxygenases 1 and 2 (COX-1, COX-2), and 15-lipoxygenase (15-LO)) in normal subjects and in patients with stable atopic asthma and stable cystic fibrosis.Reverse transcription polymerase chain reaction (RT-PCR) was used to examine the expression of total RNA for 5-LO, FLAP, COX-1, COX-2, and 15-LO in peripheral blood polymorphonuclear cells and mononuclear cells from the three subjects groups.The expression of mRNA for 5-LO and FLAP was similar in normal subjects and in patients with asthma and cystic fibrosis. COX-1 was increased in both cell types in asthmatic patients. COX-2 and 15-LO were increased in polymorphs of patients with atopic asthma but not in mononuclear cells. COX-2 and 15-LO were undetectable in either cell type in patients with cystic fibrosis whereas COX-1 levels in polymorphs were similar to those in patients with asthma.The increased leukotriene production in asthma and cystic fibrosis is not explained by an increase in transcription of 5-LO and FLAP. Transcription of 15-LO and COX-2 is increased in atopic asthma. Transcription of COX-1 is increased in both atopic asthma and cystic fibrosis.
Molecular biology: principles and applications Analysis of protein synthesis Methods for in situ hybridization Finding disease genes Protein and gene polymorphisms Site directed mutagenesis Tissue specificity Applications of molecular biology to lung disease: bacterial infection Molecular biology and respiratory disease Application to pathology Oncogenes, cancer and growth factors Molecular biology of lung receptors The regulation of collagen and elastin gene expression in normal lung and during pulmonary disease Transepithelial transport of secretory immunoglobulins Heat shock proteins Molecular cellular and genetic studies of atopic disease Interleukins in the pulmonary inflammatory response Gene therapy
No abstract is provided for this article.
There are many examples of meta-languages to describe computer network models, experiment designs, data formats, and visualization parameters. It is clear that the field recognizes the importance and benefits of a concise, portable and precise problem description, abstracted from the native represen
