Animal studies have demonstrated that synchronised coronary sinus retroperfusion with arterial blood can provide effective perfusion of ischaemic myocardium. Preliminary clinical studies have shown that the technique can also be used with safety in human beings, and in the present study its effectiveness was assessed in three patients undergoing repeated coronary artery occlusions during percutaneous transluminal coronary angioplasty. Arterial blood was removed via an 8F catheter positioned in the femoral artery and delivered by a retroperfusion pumping system to a 7F retroperfusion balloon catheter positioned in the anterior cardiac vein. Ischaemia-related indices were monitored both before and during coronary sinus retroperfusion. These indices included high fidelity left ventricular pressure recordings and pressure derived indices (including velocities of isovolumic contraction and relaxation), as well as electrocardiographic changes and symptoms. Analysis of these variables showed that the ischaemic changes induced during coronary artery occlusion were not prevented by this type of coronary sinus retroperfusion. There was no major complication in any of the patients. It may be that adaptation of the technique or the use of alternative end points will establish a benefit, but further modifications of the delivery system are necessary for effective clinical use.
Structural steel design codes generally use design methods requiring the determination of two key reference loads: (i) the plastic collapse load and (ii) the elastic buckling load. Using these two key reference loads, the element slenderness can be determined and member resistances can be obtained through buckling curves. Both of these reference loads can be estimated either through simplified analytical expressions or numerical analysis. In the cases of uniform loading, regular geometry and straightforward boundary conditions, the former approach is well suited, while for problems leading to complex non-uniform stress distributions, such as members under concentrated transverse loading, numerical solutions are often necessary. Using numerical methods, the plastic collapse loads can be obtained through Materially Nonlinear Analyses (MNA). However, since the development of a plastic collapse mechanism brings about large localised strains and extensive plasticity, a MNA can abort prematurely due to its failure to satisfy the necessary convergence criteria or the obtained load-deformation path can flatten out only after unrealistically large deformations, resulting in misleading predictions of the plastic collapse loads. In this paper, an extrapolation technique is recommended for the determination of plastic collapse loads from MNA for plate elements and cold-formed sections under concentrated transverse loading. The proposed procedure is based on the Modified Southwell (MS) Plot, originally proposed for the identification of critical loads.
Structural components designed to absorb energy and shield a more valuable structure ideally require mechanical properties that combine a relatively high load-carrying capacity followed by a practically zero stiffness. This ensures that a specified energy quantity may be absorbed within a limited displacement and that any stress transfer to the valuable structure is minimized. Material damage has been historically mobilized to provide such properties, but this obviously renders such components to be single-use. By contrast, mobilization of elastic instability can also provide the desired combination of properties but without necessarily damaging the material. This reveals an intriguing possibility of such components being potentially repairable and theoretically re-usable with no significant loss in performance. A series of analytical, finite-element and experimental studies are presented for a bespoke mechanical metamaterial arrangement that is designed to buckle sequentially and behave with the desired 'high strength-low stiffness' characteristic. It is found that the various axial and rotational stiffnesses associated with the geometric arrangement and its constituent connections may be tuned to provide the desired mechanical behaviour within the elastic range and delay the onset of significant damage, thereby rendering the concept of harnessing instability to be feasible.
Background Diabetes mellitus increases adverse outcomes after coronary revascularization; however, the impact of metabolic syndrome is unclear. We examined the impact of diabetes and metabolic syndrome on coronary artery bypass graft surgery (CABG) and stenting outcomes to determine the optimal revascularization option for the treatment of complex coronary artery disease. Methods Patients (n = 1,800) with left main or three-vessel disease or both were randomly allocated to treatment with a TAXUS Express2 paclitaxel-eluting stent (PES) or CABG, and were included in predefined nondiabetic (n = 1,348) or diabetic subgroups (n = 452); 258 patients with diabetes also had metabolic syndrome. Results Among diabetic patients, the 3-year major adverse cardiac and cerebrovascular event (MACCE) rate (22.9% CABG, 37.0% PES; p = 0.002) and revascularization rate (12.9% CABG, 28.0% PES; p < 0.001) were higher after PES treatment. Diabetes increased MACCE rates among PES-treated patients, but had little impact on results after CABG. Compared with CABG, PES treatment yielded comparable MACCE in diabetic patients (30.5% versus 29.8%, p =0.98) and nondiabetic patients (20.2% versus 20.3%, p =0.99) with low Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery (SYNTAX) study scores of 22 or less. For patients with SYNTAX Scores of 33 or greater, MACCE rates were lower with CABG (18.5% versus 45.9%, p < 0.001 diabetic; 19.8% versus 30.0%, p = 0.01 nondiabetic). Metabolic syndrome did not significantly predict MACCE or repeat revascularization. Conclusions These exploratory analyses suggest that among diabetic patients with complex left main or three-vessel disease, or both, 3-year MACCE is higher after PES compared with CABG. Although PES is a potential treatment option in patients with less complex lesions, CABG should be the revascularization option of choice for patients with more complex anatomic disease, especially with concurrent diabetes. Metabolic syndrome had little impact on 3-year outcomes.
No abstract is provided for this article.
Glucocorticoids are the most effective anti-inflammatory therapy for asthma yet are relatively ineffective in chronic obstructive pulmonary disease. Glucocorticoids suppress inflammation via several molecular mechanisms. Glucocorticoids suppress the multiple inflammatory genes that are activated in chronic inflammatory diseases, such as asthma, by reversing histone acetylation of activated inflammatory genes through binding of ligand-bound glucocorticoid receptors (GR) to co-activator molecules and recruitment of histone deacetylase-2 to the activated inflammatory gene transcription complex (trans-repression). At higher concentrations of glucocorticoids GR homodimers interact with DNA recognition sites to activate transcription through increased histone acetylation of anti-inflammatory genes and transcription of several genes linked to glucocorticoid side effects (trans-activation). Glucocorticoids also have post-transcriptional effects and decrease stability of some pro-inflammatory mRNA species. Decreased glucocorticoid responsiveness is found in patients with severe asthma and asthmatics who smoke, as well as in all patients with chronic obstructive pulmonary disease. Several molecular mechanisms of glucocorticoid resistance have now been identified which involve post-translational modifications of GR. Histone deacetylase-2 is markedly reduced in activity and expression as a result of oxidative/nitrative stress so that inflammation becomes resistant to the anti-inflammatory actions of glucocorticoids. Dissociated glucocorticoids and selective GR modulators which show improved trans-repression over trans-activation effects have been developed to reduce side effects, but so far it has been difficult to dissociate anti-inflammatory effects from adverse effects. In patients with glucocorticoid resistance alternative anti-inflammatory treatments are being investigated as well as drugs that may reverse the molecular mechanisms of glucocorticoid resistance.
