5 research outputs found

    Cell-Specific Gene Deletion Reveals the Antithrombotic Function of COX1 and Explains the Vascular COX1/Prostacyclin Paradox.

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    Rationale: Endothelial cells (ECs) and platelets, which respectively produce antithrombotic prostacyclin and prothrombotic thromboxane A2, both express COX1 (cyclooxygenase1). Consequently, there has been no way to delineate any antithrombotic role for COX1-derived prostacyclin from the prothrombotic effects of platelet COX1. By contrast, an antithrombotic role for COX2, which is absent in platelets, is straightforward to demonstrate. This has resulted in an incomplete understanding of the relative importance of COX1 versus COX2 in prostacyclin production and antithrombotic protection in vivo. Objective: We sought to identify the role, if any, of COX1-derived prostacyclin in antithrombotic protection in vivo and compare this to the established protective role of COX2. Methods and Results: We developed vascular-specific COX1 knockout mice and studied them alongside endothelial-specific COX2 knockout mice. COX1 immunoreactivity and prostacyclin production were primarily associated with the endothelial layer of aortae; freshly isolated aortic ECs released >10-fold more prostacyclin than smooth muscle cells. Moreover, aortic prostacyclin production, the ability of aortic rings to inhibit platelet aggregation and plasma prostacyclin levels were reduced when COX1 was knocked out in ECs but not in smooth muscle cells. When thrombosis was measured in vivo after FeCl3 carotid artery injury, endothelial COX1 deletion accelerated thrombosis to a similar extent as prostacyclin receptor blockade. However, this effect was lost when COX1 was deleted from both ECs and platelets. Deletion of COX2 from ECs also resulted in a prothrombotic phenotype that was independent of local vascular prostacyclin production. Conclusions: These data demonstrate for the first time that, in healthy animals, endothelial COX1 provides an essential antithrombotic tone, which is masked when COX1 activity is lost in both ECs and platelets. These results help us define a new 2-component paradigm wherein thrombotic tone is regulated by both COX1 and COX2 through complementary but mechanistically distinct pathways

    Elective Thoracic Aortic Aneurysm Surgery: A Tertiary Center Experience

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    Background A thoracic aortic aneurysm (TAA) is a diseased expansion of the thoracic aorta. There is morbidity associated with a dilated aorta, as well as significant mortality. Open thoracic surgery is the fundamental management for proximal lesions, offering definitive treatment with excellent results. This study aimed to summarize preoperative data and operative outcomes of patients who underwent TAA repair at our institution. Methods Data were retrospectively collected from 234 patients that underwent elective open thoracic surgery at University Hospital Southampton for TAA disease, between 2015 and 2019. Demographics, clinical factors, surgical details, as well as outcome measures, were gathered. Results There were 166 males and 68 females, with an overall mean age of 66 years. The breakdown of operations comprised 105 aortic roots, 171 ascending aorta, 20 aortic arch, and 12 descending aorta cases. The mean follow-up was 370 days. 30-day mortality was 5.13%. Mortality was associated with female gender, aortic root surgery, and prosthetic valves. Mean aortic diameters at the time of surgery for the non-genetic aortopathy and genetic aortopathy groups were respectively 4.93cm and 4.63cm in the aortic root, 5.56cm and 4.88cm in the ascending aorta, 5.08cm and 3.87cm in the aortic arch, and 6.63cm and 5.50cm in the descending aorta. Conclusion Several factors are associated with complications and morbidity, which should be considered when discussing the risks of intervention with patients. There were no neuroprotective strategies that altered post-operative neurological function. Current practice in our unit fits in with current international guidance

    Experimental and analytical investigation of improved behavior of existing steel connections by adding self-centering capabilities

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    This study presents a new post-tensioning configuration for enhancing the seismic performance of existing steel bolted connections. The nonlinear behavior of the proposed post-tensioned connection was investigated through experimental and analytical programs. Different post-tensioning strand configurations were installed on top-and-seat angle connections with different strand length, strand number, and initial post-tensioning force. Data from the tested post-tensioned connections showed a significant improvement in the nonlinear behavior when compared to their non-post-tensioned counterparts. This improvement was achieved by increasing the overall stiffness and strength in addition to providing self-centering capabilities that could limit the residual drifts for the retrofitted moment-resisting frames after a strong earthquake. An analytical representation of the proposed connection is presented and modified considering the effect of the strand relaxation. The derived analytical equation accurately represented the response of the post-tensioned beam-to-column connection in terms of the moment-rotation relationship and it could be used for the analysis and design of post-tensioned connections subjected to large deformations
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