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Forisomes are large mechanoprotein complexes found solely in legumes such as Medicago truncatula. They comprise several ���sieve element occlusion by forisome��� (SEO-F) subunits, with MtSEO-F1 as the major structure-forming component. SEO-F proteins possess three conserved domains ���an N-terminal domain (SEO-NTD), a potential thioredoxin fold, and a C-terminal domain (SEO-CTD)��� but structural and biochemical data are scarce and little is known about the contribution of these domains to forisome assembly. To identify key amino acids involved in MtSEO-F1 dimerization and complex formation, we investigated protein-protein interactions by bimolecular fluorescence complementation and the analysis of yeast two-hybrid and random mutagenesis libraries. We identified a SEO-NTD core region as the major dimerization site, with abundant hydrophobic residues and rare charged residues suggesting dimerization is driven by the hydrophobic effect. We also found that ~45% of the full-length MtSEO-F1 sequence must be conserved for higher-order protein assembly, indicating that large interaction surfaces facilitate stable interactions, contributing to the high resilience of forisome bodies. Interestingly, the removal of 62 amino acids from the C-terminus did not disrupt forisome assembly. This is the first study unraveling interaction sites and mechanisms within the MtSEO-F1 protein at the level of dimerization and complex formation. �� 2018

Symptomatic patients with chronic thromboembolic disease (CTED) without pulmonary hypertension often show an excessive increase in mean pulmonary arterial pressure (MPAP) during exercise.We report on the impact of pulmonary endarterectomy (PEA) on pulmonary haemodynamics in a prospective series of 32 consecutive CTED patients who underwent PEA. All patients had a comprehensive diagnostic work-up including right heart catheterisation at baseline and 12 months after PEA. Furthermore, in 12 patients exercise right heart catheterisation was performed before and after PEA.After PEA, MPAP was lower at rest (20±3versus17±3 mmHg; p=0.008) and during maximal exercise (39±8versus31±6 mmHg; p=0.016). The mean total pulmonary resistance (TPR) decreased from 3.6±0.8 Wood Units (WU) pre-operatively to 2.7±0.7 WU 1 year after PEA (p=0.004) and the mean slope of the MPAP/cardiac output (CO) relationship decreased from 3.6±1.0 to 2.3±0.8 WU (p=0.002). Peak oxygen uptake increased from 1.2±0.4 to 1.5±0.3 L·min−1(p=0.014) and ventilatory equivalents of carbon dioxide decreased from 39±2 to 30±2 (p=0.002). There was a significant improvement in quality of life assessed by the Cambridge Pulmonary Hypertension Outcome Review questionnaire.In CTED patients, PEA resulted in haemodynamic and clinical improvements. The means of TPR and MPAP/CO slopes decreased to

Because of the substantial risk of thromboembolism early after valve replacement, perioperative initiation of anticoagulation is necessary, despite the increased risk for bleeding. Anticoagulation should be initiated within 24 h after the procedure with unfractionated heparin or low-molecular-weight heparin (LMWH). Subcutaneous LMWH appears more beneficial than intravenous heparin therapy, but this approach requires further evaluation. Oral anticoagulants, preferably at low dosage, are added following the removal of chest tubes. Heparin anticoagulation is monitored by checking the activated partial thromboplastin time or anti-Xa activity, and the International Normalized Ratio (INR) is used to measure the effects of oral anticoagulants. Heparin treatment should be continued until the INR is stable in the therapeutic range in order to avoid hypercoagulable conditions caused by varying degrees of decay in coagulation factors.

Background Ischaemia-reperfusion injury is still a major problem after lung transplantation. Several reports describe the benefits of controlled graft reperfusion. In this study the role of length of the initial pressure-controlled reperfusion (PCR) was evaluated in a model of isolated, buffer-perfused rabbit lungs. Methods Heart-lung blocks of 25 New Zealand white rabbits were used. After measurement of baseline values (haemodynamics and gas exchange) the lungs were exposed to 120 minutes of hypoxic warm ischaemia followed by repeated measurements during reperfusion. Group A was immediately reperfused using a flow of 100 ml/min whereas groups B, C and D were initially reperfused with a maximum pressure of 5 mmHg for 5, 15 or 30 minutes, respectively. The control group had no period of ischaemia or PCR. Results Uncontrolled reperfusion (group A) caused a significant pulmonary injury with increased pulmonary artery pressures (PAP) and pulmonary vascular resistance and a decrease in oxygen partial pressure (PO2), tidal volume and in lung compliance. All groups with PCR had a significantly higher PO2 for 5 to 90 min after start of reperfusion. At 120 min there was also a significant difference between group B (264 ± 91 mmHg) compared to groups C and D (436 ± 87 mmHg; 562 ± 20 mmHg, p < 0.01). All PCR groups showed a significant decrease of PAP compared to group A. Conclusion Uncontrolled reperfusion results in a severe lung injury with rapid oedema formation. PCR preserves pulmonary haemodynamics and gas exchange after ischaemia and might allows for recovery of the impaired endothelial function. 30 minutes of PCR provide superior results compared to 5 or 15 minutes of PCR.

BACKGROUND Degeneration remains the major drawback of bioprostheses. Among various concepts to mitigate degeneration, the use of autologous pericardium for intraoperative construction of aortic valves (ATCV) was revived recently. Based on in-vivo studies the problem of tissue failure was claimed to be oversome by short immersion in glutaraldehyde. METHODS Two often ATCV implanted 1994-1996 had to be replaced because of valvular insufficiency due to leaflet shrinkage or tearing. Pathophysiology of failure was evaluated by light microscopy and immune histology, scanning electron microscopy (SEM) and determination of tissue calcium content (AAS). RESULTS AAS revealed high calcium levels in the shrunken and low levels in the torn leaflets. Histology demonstrated extensive fiber degeneration without inflammation in the destructed and moderate degeneration in the intact leaflets. SEM showed smooth surfaces in the 'normal' and exposure of collagen in the degenerated leaflet associated with calcification. Tears occurred close to the stents. CONCLUSIONS Failure of ATCV is characterised by either shrinkage and calcification despite a short tanning or by tearing related to the stent design. Clinical use of ATCV cannot be recommended at present.

The use of biologic heart valve prostheses is decreasing because of the high incidence of failure of these bioprostheses resulting from tissue degeneration or tearing. Immunologie reactions might play a decisive role in this process. The present experimental and clinical studies were conducted to investigate the relevance of immunologie reactions to the tissue failure of glutaraldehydetanned bovine pericardial and porcine valves. Specimens of the two different types of valve material were implanted in the abdominal muscles of rats. Enzyme-linked immunosorbent assays and tritiated thymidine incorporation tests were performed to detect specific antibodies and activated T cells. All specimens were studied histologically. Identical enzyme-linked immunosorbent assays and tritiated thymidine incorporation tests were performed in 29 patients with bioimplants and in 48 controls. Twenty explanted bioprostheses were investigated using histologic and immune histologie methods. The results of the enzyme-linked immunosorbent assays and lymphocyte proliferation tests showed that glutaraldehyde-tanned bovine pericardial valves can provoke cellular and humoral immunologic reactions in rats and human beings. In explanted bovine valves, macrophages were found invading and degrading implant collagen, starting from surface lesions. The combination of the formation of mechanical lesions, the development of cellular infiltrates, and collagen disruption strongly indicates that initial surface lesions initiate the immunologic reactions in bovine pericardial valves as the result of the exposure of incompletely tanned collagen. These immune responses might accelerate tissue degeneration. Porcine valves do not provoke immunologic reactions.

Ein betrachtlicher Anteil biologischer Herzklappenprothesen mus innerhalb der er¬sten Dekade nach Implantation wegen Gewebedegeneration und Verkalkungen ausge-tauscht werden [2]. Die Pathophysiologie der zugrundeliegenden Prozesse ist im Detail noch unklar [1]. Immunreaktionen als eine Ursache werden diskutiert: das histologi¬sche Bild mancher wegen Degeneration explantierter Bioprothese zeigt entzundliche Infiltrate mit Zerstorung der Kollagenstruktur. Eine wichtige Einflusgrose fur die Progredienz dystropher Verkalkungen der Implantate ist der Einstrom von Plasmapro¬teinen in das avitale Fasergerust mit Anlagerung von Kalzium.