Selective anticoagulation with active site-blocked factor IXA suggests separate roles for intrinsic and extrinsic coagulation pathways in cardiopulmonary bypass

BACKGROUND: Multiple stimuli converge in cardiopulmonary bypass to create a tremendous prothrombotic stimulus. The ideal anticoagulant for cardiopulmonary bypass should selectively target only the intravascular stimuli, thereby eliminating pathologic clotting in the bypass circuit while preserving hemostasis in the thoracic cavity. We propose the inhibition of factor IX as such a targeted anticoagulant strategy. METHODS: We prepared an inhibitor of activated factor IX and applied it to a primate model of cardiopulmonary bypass to confirm the anticoagulant efficacy of activated factor IX in this setting and to assess more subtle markers of thrombin generation, macrophage procoagulant activity, and cellular tissue factor expression. Seven baboons that received activated factor IX (460 microg/kg) and 7 that received heparin (300 IU/kg) and protamine underwent cardiopulmonary bypass for 90 minutes and were followed after the operation for 3 hours. RESULTS: Analysis of plasma factor IX activity demonstrated adequate inhibition (<20%) of factor IX throughout cardiopulmonary bypass. Activated factor IX-treated baboons demonstrated similar circuit patency to heparin-treated baboons but had significantly diminished intraoperative blood loss. Preservation of extravascular hemostasis was further demonstrated in activated factor IX-treated animals by (1) significantly increased levels of thrombin-antithrombin III complex and prothrombin activation peptide (F1+2) without intravascular thrombosis, (2) significantly greater macrophage procoagulant activity in pericardial-derived monocytes, and (3) immunohistochemical evidence of tissue factor expression in pericardial mesothelial cells and macrophages. CONCLUSIONS: Anticoagulation with activated factor IX allows for intravascular anticoagulation with maintenance of extravascular hemostasis. These findings suggest activated factor IX as an agent that not only exemplifies a targeted approach to selective anticoagulation in cardiac surgery but also further characterizes the procoagulant milieu during cardiopulmonary bypass.     

Optimization of the adhesive joint Iosipescu specimen for pure shear test

This paper reviews some of the difficulties encountered in achieving a uniform stress distribution within the adhesive layer of bonded Iosipescu shear test specimens. The asymptotic singular stress field at the terminus of a skewed bimaterial interface, intersecting the straight free surface of the wedge, has been studied macroscopically and microscopically using the finite element method (FEM) and the finite element iterative method (FEIM). Different mechanical properties of the adhesives and adherends, and various skewed interface angles have been considered in this study. A critical skewed interface angle, _c=126°, has been found beyond which the interfacial stress singularity vanishes. This critical angle is independent of the elastic properties of the adhesives and adherends. Based on the results obtained in the present investigation, in conjunction with recently reported research on sharp notches [7, 21–23], an optimized adhesive joint Iosipescu specimen geometry is proposed. This specimen should be capable of generating a uniform shear stress state within its adhesive layer under pure shear loading conditions.     

Recent trends in PEM fuel cell-powered hybrid systems: Investigation of application areas,design architectures and energy management approaches

Recently, the renewable energy issue is becoming significant due to increasing power demand, instability of the rising oil prices and environmental problems. Among the various renewable energy sources, fuel cell (FC) technology has received considerable attention as an alternative to the conventional power units due to its higher efficiency, clean operation and cost-effective supply of power demanded by the consumers. Particularly, proton exchange membrane (PEM) FC technology plays a leading role for many applications when comparing with other competitive types of FCs. PEMFCs have recently passed the test or demonstration phase and have partially reached the commercialization stage due to the impressive worldwide research effort. Besides, providing a hybrid system by integration of PEMFC with an auxiliary power source may provide better results considering the issues of performance and component durability. This paper presents a comprehensive review of the recent trends in PEMFC powered hybrid systems including a detailed explanation of application areas and design architectures with different power electronics interfaces as well as the energy management methods utilized in the daily life and taking part in the literature.