Publications

Intracoronary Heparin Delivery in Humans

Background Inefficacy of systemic drug administration for restenosis prevention may partially relate to insufficient local drug concentration. This study aimed to evaluate the acute feasibility and long-term outcome of using an infusion-perfusion coil balloon, Dispatch. Methods and Results In 22 patients after balloon angioplasty, the coil balloon was studied for (1) feasibility of local heparin delivery, (2) symptoms and signs of ischemia during prolonged deployment compared with angioplasty balloon occlusion, (3) coronary pressure and flow distal to the inflated device, and (4) long-term clinical and angiographic results. During prolonged intracoronary deployment of the coil balloon (29±8 minutes), 5 of 22 patients developed mild chest pain versus 20 of 22 during angioplasty (275±283 seconds). Neither hemodynamic nor vectorcardiographic signs of ischemia were detected, in contrast to angioplasty balloon occlusion. Baseline flow across the coil balloon was 44±31 mL/min, increasing by a factor of 1.8±0.7 during pharmacologically induced hyperemia. A mean volume of 14.2±6.1 mL containing 1416±608 IU of heparin was infused locally at a pressure of 122±54 mm Hg. At 7±1-month follow-up, 1 asymptomatic patient had died, and of the remaining 21, 17 (81%) were asymptomatic. Angiographic follow-up was obtained in 15 of 21 patients (71%), including all 4 symptomatic patients. Mean minimal luminal diameter after the procedure was 2.16±0.49 mm and at follow-up, 1.89±0.45 mm, which corresponds to a restenosis rate (diameter stenosis ≥50%) of 7% (1/15). Conclusions Intracoronary use of the coil balloon after balloon angioplasty proved to be feasible and subjectively as well as objectively well tolerated during prolonged deployment by virtue of its perfusion properties. High volumes of heparin solution can be infused locally at very low pressure. No unfavorable clinical or angiographic long-term effects were observed.

Meet Our Editorial Board Member

Videodensitometry in percutaneous coronary interventions: a critical appraisal of its contributions and limitations

No abstract is provided for this article.

TCT-309 Angiography-derived fractional flow reserve in the SYNTAX II trial: diagnostic accuracy of QFR and clinical prognostic value of functional SYNTAX score derived from QFR

No abstract is provided for this article.

Expression profiling identifies key genes and biological functions associated with eosinophilic esophagitis in human patients

Introduction Eosinophilic Esophagitis (EoE) is a chronic allergic disease characterized by progressive inflammation of the esophageal mucosa. This chronic inflammatory disorder affects up to 50 per 100,000 individuals in the United States and Europe yet is limited in treatment options. While the transcriptome of EoE has been reported, few studies have examined the genetics among a cohort including both adult and pediatric EoE populations. To identify potentially overlooked biomarkers in EoE esophageal biopsies that may be promising targets for diagnostic and therapeutic development. Methods We used microarray analysis to interrogate gene expression using esophageal biopsies from EoE and Control subjects with a wide age distribution. Analysis of differential gene expression (DEGs) and prediction of impaired pathways was compared using conventional transcriptome analysis (TAC) and artificial intelligence-based (ADVAITA) programs. Principal Components Analysis revealed samples cluster by disease status (EoE and Control) irrespective of clinical features like sex, age, and disease severity. Results Global transcriptomic analysis revealed differential expression of several genes previously reported in EoE ( CCL26, CPA3, POSTN, CTSC, ANO1, CRISP3, SPINK7 ). In addition, we identified differential expression of several genes from the MUC and SPRR families, which have been limited in previous reports. Discussion Our findings suggest that there is epithelial dysregulation demonstrated by DEGs that may contribute to impaired barrier integrity and loss of epidermal cell differentiation in EoE patients. These findings present two new gene families, SPRR and MUC , that are differentially expressed in both adult and pediatric EoE patients, which presents an opportunity for a future therapeutic target that would be useful in a large demographic of patients.

Hydrogen Peroxide in Exhaled Breath Condensate in Patients with Asthma

New drugs and targets for asthma and COPD

Muscarinic receptors in airways: recent developments

Recently there have been important advances in our understanding of muscarinic receptors in airways that have important implications for understanding airway control and for future therapy of airway diseases. The transduction mechanisms involved in muscarinic receptor activation are now better understood. Receptor-linked phosphoinositide hydrolysis leads to release of calcium ions from intracellular stores, resulting in contraction of airway smooth muscle. At least five subtypes of muscarinic receptor have now been cloned, although only three subtypes can be distinguished pharmacologically. M1 receptors are facilitatory to neurotransmission in airway parasympathetic ganglion cells and have also been identified in airway submucosal glands and on the alveolar walls of human lung. M2 receptors are located on postganglionic nerves and function as powerful feedback inhibitory receptors (autoreceptors) that are likely to be involved in modulation of reflex bronchoconstriction. These receptors may be dysfunctional in asthmatic airways. M3 receptors are present on airway smooth muscle and submucosal glands and mediate the classical muscarinic effects in airways. Molecular biology techniques should now allow further study of the factors that regulate transcription and expression of muscarinic receptors in airways.

MAKING LIGHT OF FISH BONES

A new development which has emerged from this Department marks the beginning of an expansion into other foods besides cereals. It also marks the beginning of the wider use of fluorescence in monitoring and controlling food processing.

Effects of Infused Adenosine on the Cardiovascular Responses to Orthostasis in Man

Conference Abstract| January 01 1987 Effects of Infused Adenosine on the Cardiovascular Responses to Orthostasis in Man B. Clarke; B. Clarke 1Department of Clinical Pharmacology, Brompton Hospital, Cardiothoracic Institute, London UK Search for other works by this author on: This Site PubMed Google Scholar T-B. Conradson; T-B. Conradson 1Department of Clinical Pharmacology, Brompton Hospital, Cardiothoracic Institute, London UK Search for other works by this author on: This Site PubMed Google Scholar C.M.S. Dixon; C.M.S. Dixon 1Department of Clinical Pharmacology, Brompton Hospital, Cardiothoracic Institute, London UK Search for other works by this author on: This Site PubMed Google Scholar N. Dalton; N. Dalton **Department of Paediatrics, Guy's Hospital, London UK Search for other works by this author on: This Site PubMed Google Scholar P.J. Barnes P.J. Barnes 1Department of Clinical Pharmacology, Brompton Hospital, Cardiothoracic Institute, London UK Search for other works by this author on: This Site PubMed Google Scholar Clin Sci (Lond) (1987) 72 (s16): 9P. https://doi.org/10.1042/cs072009P Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share MailTo Twitter LinkedIn Cite Icon Cite Get Permissions Citation B. Clarke, T-B. Conradson, C.M.S. Dixon, N. Dalton, P.J. Barnes; Effects of Infused Adenosine on the Cardiovascular Responses to Orthostasis in Man. Clin Sci (Lond) 1 January 1987; 72 (s16): 9P. doi: https://doi.org/10.1042/cs072009P 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.

Inhaled Corticosteroids Are Not Beneficial in Chronic Obstructive Pulmonary Disease

Alveolar Macrophages as Orchestrators of COPD

Alveolar macrophages play a critical role in the pathophysiology of COPD and are a major target for future anti‐inflammatory therapy. Macrophage numbers are markedly increased in the lung and alveolar space of patients with COPD and are localized to sites of alveolar destruction. The increased numbers of macrophages may result from increased recruitment of blood monocytes, prolonged survival in the lung and to a lesser extent to increased proliferation in the lung. Alveolar macrophages from COPD patients have an increased baseline and stimulated secretion of inflammatory proteins, including certain cytokines, chemokines, reactive oxygen species and elastolytic enzymes, which together could account for all of the pathophysiological features of COPD. Alveolar macrophages form COPD appear to be resistant to the anti‐inflammatory effects of corticosteriods and this is linked to reduced activity and expression of histone deacetylase 2, a nuclear enzyme that switches off inflammatory genes activated through the transcription factor nuclear factor‐KB. Alternative anti‐inflammatory therapies that inhibit macrophages are therefore needed in the future to deal with the chronic inflammation of COPD. These drugs may include resveratrol, theophylline derivatives, MAP kinase inhibitors and phosphodiesterase‐4 inhibitors.

Validation of the SYNTAX Revascularization Index to Quantify Reasonable Level of Incomplete Revascularization After Percutaneous Coronary Intervention

Incomplete revascularization is common after percutaneous coronary intervention (PCI). Whether a “reasonable” degree of incomplete revascularization is associated with a similar favorable long-term prognosis compared with complete revascularization remains unknown. We sought to quantify the proportion of coronary artery disease burden treated by PCI and evaluate its impact on outcomes using a new prognostic instrument—the Synergy Between PCI with Taxus and Cardiac Surgery (SYNTAX) Revascularization Index (SRI). The baseline SYNTAX score (bSS), the residual SYNTAX score, and the delta SYNTAX score (ΔSS) were determined from 888 angiograms of patients enrolled in the prospective SYNTAX trial. The SRI was then calculated for each patient using the following formula: SRI = (ΔSS/bSS]) × 100. Outcomes were examined according to the proportion of revascularized myocardium (SRI = 100% [complete revascularization], 50% to <100%, and <50%). The Youden index for the SRI was computed to identify the best cutoff for 5-year all-cause mortality. The mean bSS was 28.4 ± 11.5, and after PCI, the mean ΔSS was 23.8 ± 10.9 and the mean residual SYNTAX score was 4.5 ± 6.9. The mean SRI was 85.3 ± 21.2% and was 100% in 385 patients (43.5%), <100% to 50% in 454 patients (51.1%), and <50% in 48 patients (5.4%). Five-year adverse outcomes, including death, were inversely proportional to the SRI. An SRI cutoff of <70% (present in 142 patients [16.0%] after PCI) had the best prognostic accuracy for prediction of death and, by multivariable analysis, was an independent predictor of 5-year mortality (hazard ratio [HR] 4.13, 95% confidence interval [CI] 2.79 to 6.11, p <0.0001). In conclusion, the SRI is a newly described method for quantifying the proportion of coronary artery disease burden treated by PCI. The SRI is a useful tool in assessing the degree of revascularization after PCI, with SRI ≥70% representing a “reasonable” goal for patients with complex coronary artery disease.

The future of BRS in bifurcations

Bioresorbable scaffolds (BRS) provide a new tool for percutaneous treatment of coronary stenosis. Initially, relatively simple coronary artery lesions were treated with this novel technology; nowadays, we have gained more experience with a wide variety of lesions, including bifurcation lesions. Data are limited in terms of the use of BRS in coronary bifurcation lesions, although it has been demonstrated that over time the bioresorbable struts are replaced by a tissue bridge resembling a "neo-carina". Furthermore, data are emerging about the endothelial shear stress (ESS) alterations and blood flow patterns after scaffold implantation. It is likely that ESS and blood flow determinations will guide correct future bifurcation techniques. In the future, BRS with thinner struts and more resistant to fracture are likely to improve bifurcation treatment with BRS.

Faster Rise of Exhaled Breath Temperature in Asthma

In asthma there is increased vascularity of the airway mucosa, altering heat loss in the airways. We hypothesized that as a result of these inflammatory changes, asthmatic patients would have elevated rates of the exhaled air temperature increase (Deltae degrees T). We measured Deltae degrees T in 18 asthmatic subjects (mean age +/- SEM, 38 +/- 8 yr; 9 male, FEV(1) 74 +/- 10%) and 16 normal volunteers (mean age +/- SEM, 33 +/- 3 yr) and compared it with exhaled nitric oxide (NO) as a marker of inflammation. Deltae degrees T was measured during a flow- and pressure-controlled single exhalation with a fast response (1 ms) thermometer. The end-expiratory plateau temperature was similar in asthmatic compared with normal subjects (35.75 +/- 0.6 degrees C and 34.45 +/- 0.8 degrees C, p > 0.05). However, Deltae degrees T was greater in asthmatic subjects (8.17 +/- 0.83 degrees C/s and 4.12 +/- 0.41 degrees C/s, p < 0.01) and correlated with NO (r = 0.65, p = 0.034). Deltae degrees T was increased in normal subjects (from 4.28 +/- 0.8 degrees C/s to 7.60 +/- 0.5 degrees C/s, p < 0.01) but not in asthmatic patients (from 8.28 +/- 0.41 degrees C/s to 8.80 +/- 0.41 degrees C/s, p > 0.05) after the inhalation of albuterol, indicating that Deltae degrees T may reflect bronchial blood flow. Asthmatic subjects have elevated Deltae degrees T. This may represent a novel, noninvasive means of measuring airway blood flow and inflammation in asthma.

Percutaneous Coronary Intervention or Coronary Artery Bypass Graft for Unprotected Left Main Coronary Artery Disease: The Endless Debate

No abstract is provided for this article.

Regional wall motion from radiopaque markers after intravenous and intracoronary injections of nifedipine.

SlUMMARY In 11 patients, 1 mg of i.v.nifedipine was administered over 3 minutes and regional wall motion was studied during atrial pacing.The dominant effect of nifedipine at basal heart rate (HR) was a lowering of peak left ventricular pressure (152 to 128 mm Hg) with an increase in HR from 70 to 86 beats/min.During pacing, nifedipine produced (p < 0.02) a similar reduction in pressure at all rates, which is a mechanism reduc- ing or sparing myocardial oxygen consumption.At the highest paced rate, the maximal velocity (Vmax) of the contractile element was significantly (p < 0.02) increased from 61 to 68 sec-' and the regional shortening frac- tions were increased over the entire pacing range: basal HR, 13.7% to 14.6% (p < 0.025); HR 120 beats/min, 11.6% to 13.5% (p < 0.005); maximal HR, 10.9% to 11.8% (p < 0.05).No evidence of a negative inotropic effect after i.v.administration of nifedipine was observed, myocardial oxygen consumption was probably reduced and there was an increase in regional function.Nifedipine (0.1 mg within 10 seconds) was selectively injected into bypass grafts at a constant paced rate in 10 patients.Seventeen marker pair regions were directly supplied by bypasses selectively injected with nifedipine (group A), and nine were independently perfused (group B).The pressure-derived variables showed a direct negative inotropic effect and a slowed relaxation phase.Thirty seconds after injection, minimal marker separation in group A occurred 78 msec after end-systole (ES), whereas before injection, minimal marker separation occurred 39 msec before ES (p < 0.0001).At the same time, the relation between minimal marker separation and ES in group B was unaffected.In consequence, the regional shortening fraction in group A con- tributing to left ventricular ejection decreased significantly 30 seconds after injection (-32%, p < 0.01), while that calculated simply from minimal and maximal marker separation remained unchanged (-9%, NS).Active regional contraction starting after the beginning of ejection and ending after ES must be considered as asynchrony and can be considered responsible for the slowed isovolumic contraction and relaxation of the whole ventricle.The dominant effect of i.v.nifedipine at clinical dosage levels is a lowering of systemic blood pressure, possibly reducing oxygen demand.When regionally administered, nifedipine exerts a direct negative inotropic effect, but after i.v.injection, this effect is overridden by reflex increases in contractility and in heart rate as a result of lowered systemic arterial pressure.

Vascular Responses at Proximal and Distal Edges of Paclitaxel-Eluting Stents

On the basis of brachytherapy experience, edge stenosis has been raised as a potential limitation for drug-eluting stents. We used serial intravascular ultrasound (IVUS) to prospectively analyze vessel responses in adjacent reference segments after implantation of polymer-controlled paclitaxel-eluting stents.TAXUS II was a randomized, double-blind trial with 2 consecutive patient cohorts that compared slow-release (SR) and moderate-release (MR) paclitaxel-eluting stents with control bare metal stents (BMS). By protocol, all patients had postprocedure and 6-month follow-up IVUS. Quantitative IVUS analysis was performed by an independent core laboratory, blinded to treatment allocation, in 5-mm vessel segments immediately proximal and distal to the stent. Serial IVUS was available for 106 SR, 107 MR, and 214 BMS patients. For all 3 groups, a significant decrease in proximal-edge lumen area was observed at 6 months. The decrease was comparable (by ANOVA, P=0.194) for patients in the SR (-0.54+/-2.1 mm2) and MR (-0.88+/-1.9 mm2) groups compared with the BMS (-1.02+/-1.9 mm2) group. For the distal edge, a significant decrease in lumen area was only observed with BMS (-0.91+/-2.0 mm2, P<0.0001); this decrease was significantly attenuated with SR (0.08+/-2.0 mm2) and MR (-0.19+/-1.7 mm2) stents (P<0.0001 by ANOVA). Negative vessel remodeling was observed at the proximal (-0.48+/-2.2 mm2, P=0.011) but not the distal edges of BMS and at neither edge of SR or MR stents.The marked reduction in in-stent restenosis with SR or MR stents is not associated with increased edge stenosis at 6-month follow-up IVUS. In fact, compared with BMS, there is instead a significant reduction in late lumen loss at the distal edge with TAXUS stents.