Acute perioperative-stress-induced increase of atherosclerotic plaque volume and vulnerability to rupture in apolipoprotein-E-deficient mice is amenable to statin treatment and IL-6 inhibition

Myocardial infarction and stroke are frequent after surgical procedures and consume a considerable amount of benefit of surgical therapy. Perioperative stress, induced by surgery, is composed of hemodynamic and inflammatory reactions. The effects of perioperative stress on atherosclerotic plaques are ill-defined. Murine models to investigate the influence of perioperative stress on plaque stability and rupture are not available. We developed a model to investigate the influence of perioperative stress on plaque growth and stability by exposing apolipoprotein-E-deficient mice, fed a high cholesterol diet for 7 weeks, to a double hit consisting of 30 min of laparotomy combined with a substantial blood loss (approximately 20% of total blood volume; 400 µl). The innominate artery was harvested 72 h after the intervention. Control groups were sham and baseline controls. Interleukin-6 (IL-6) and serum amyloid A (SAA) plasma levels were determined. Plaque load, vascular smooth muscle cell (VSMC) and macrophage content were quantified. Plaque stability was assessed using the Stary score and frequency of signs of plaque rupture were assessed. High-dose atorvastatin (80 mg/kg body weight/day) was administered for 6 days starting 3 days prior to the double hit. A single dose of an IL-6-neutralizing antibody or the fusion protein gp130-Fc selectively targeting IL-6 trans-signaling was subcutaneously injected. IL-6 plasma levels increased, peaking at 6 h after the intervention. SAA levels peaked at 24 h (n=4, P<0.01). Plaque volume increased significantly with the double hit compared to sham (n=8, P<0.01). More plaques were scored as complex or bearing signs of rupture after the double hit compared to sham (n=5-8, P<0.05). Relative VSMC and macrophage content remained unchanged. IL-6-inhibition or atorvastatin, but not blocking of IL-6 trans-signaling, significantly decreased plaque volume and complexity (n=8, P<0.01). Using this model, researchers will be able to further investigate the pathophysiology of perioperative plaque stability, which can result in myocardial infarction, and, additionally, to test potential protective strategies

Release of soluble vascular endothelial growth factor receptor-1 (sFlt-1) during coronary artery bypass surgery

<p>Abstract</p> <p>Background</p> <p>This study was conducted to follow plasma concentrations of sFlt-1 and sKDR, two soluble forms of the vascular endothelial growth factor (VEGF) receptor in patients undergoing coronary artery bypass graft (CABG) surgery with extracorporeal circulation (ECC).</p> <p>Methods</p> <p>Plasma samples were obtained before, during and after surgery in 15 patients scheduled to undergo CABG. Levels of sFlt-1 and KDR levels were investigated using specific ELISA.</p> <p>Results</p> <p>A 75-fold increase of sFlt-1 was found during cardiac surgery, sFlt-1 levels returning to pre-operative values at the 6^thpost-operative hour. In contrast sKDR levels did not change during surgery. The ECC-derived sFlt-1 was functional as judge by its inhibitory effect on the VEGF mitogenic response in human umbilical vein endothelial cells (HUVECs). Kinetic experiments revealed sFlt-1 release immediately after the beginning of ECC suggesting a proteolysis of its membrane form (mFlt-1) rather than an elevated transcription/translation process. Flow cytometry analysis highlighted no effect of ECC on the shedding of mFlt-1 on platelets and leukocytes suggesting vascular endothelial cell as a putative cell source for the ECC-derived sFlt-1.</p> <p>Conclusion</p> <p>sFlt-1 is released during CABG with ECC. It might be suggested that sFlt-1 production, by neutralizing VEGF and/or by inactivating membrane-bound Flt-1 and KDR receptors, might play a role in the occurrence of post-CABG complication.</p

NT-proBNP or Self-Reported Functional Capacity in Estimating Risk of Cardiovascular Events After Noncardiac Surgery

ImportanceNearly 16 million surgical procedures are conducted in North America yearly, and postoperative cardiovascular events are frequent. Guidelines suggest functional capacity or B-type natriuretic peptides (BNP) to guide perioperative management. Data comparing the performance of these approaches are scarce.ObjectiveTo compare the addition of either N-terminal pro-BNP (NT-proBNP) or self-reported functional capacity to clinical scores to estimate the risk of major adverse cardiac events (MACE).Design, Setting, and ParticipantsThis cohort study included patients undergoing inpatient, elective, noncardiac surgery at 25 tertiary care hospitals in Europe between June 2017 and April 2020. Analysis was conducted in January 2023. Eligible patients were either aged 45 years or older with a Revised Cardiac Risk Index (RCRI) of 2 or higher or a National Surgical Quality Improvement Program, Risk Calculator for Myocardial Infarction and Cardiac (NSQIP MICA) above 1%, or they were aged 65 years or older and underwent intermediate or high-risk procedures.ExposuresPreoperative NT-proBNP and the following self-reported measures of functional capacity were the exposures: (1) questionnaire-estimated metabolic equivalents (METs), (2) ability to climb 1 floor, and (3) level of regular physical activity.Main Outcome and MeasuresMACE was defined as a composite end point of in-hospital cardiovascular mortality, cardiac arrest, myocardial infarction, stroke, and congestive heart failure requiring transfer to a higher unit of care.ResultsA total of 3731 eligible patients undergoing noncardiac surgery were analyzed; 3597 patients had complete data (1258 women [35.0%]; 1463 (40.7%) aged 75 years or older; 86 [2.4%] experienced a MACE). Discrimination of NT-proBNP or functional capacity measures added to clinical scores did not significantly differ (Area under the receiver operating curve: RCRI, age, and 4MET, 0.704; 95% CI, 0.646-0.763; RCRI, age, and 4MET plus floor climbing, 0.702; 95% CI, 0.645-0.760; RCRI, age, and 4MET plus physical activity, 0.724; 95% CI, 0.672-0.775; RCRI, age, and 4MET plus NT-proBNP, 0.736; 95% CI, 0.682-0.790). Benefit analysis favored NT-proBNP at a threshold of 5% or below, ie, if true positives were valued 20 times or more compared with false positives. The findings were similar for NSQIP MICA as baseline clinical scores.Conclusions and relevanceIn this cohort study of nearly 3600 patients with elevated cardiovascular risk undergoing noncardiac surgery, there was no conclusive evidence of a difference between a NT-proBNP–based and a self-reported functional capacity–based estimate of MACE risk.Trial RegistrationClinicalTrials.gov Identifier: NCT0301693

A Slavery Altar in the Temple of Liberty: The Politics of Daniel Webster’s Monument in Antebellum Boston

Over the past decade, public monuments have become an increasingly controversial subject in American political culture. This debate has focused primarily on Confederate monuments built after the U.S. Civil War and statues of other individuals with historical ties to slavery. Advocates for removal claim these monuments honor unworthy figures. Their adversaries worry that removing them is revisionist. Historical scholarship offers insights into the politics of public memory in the United States. They describe commemoration as a realm of conflict between competing groups who weaponize the past to shape their contemporary politics. However, these macro-studies have dedicated little attention to the construction of monuments themselves. The purpose of this project is to view monuments not solely as physical markers of the past, but also as complex historical documents. This study analyzes a unique statue raised in Boston, Massachusetts shortly before the U.S. Civil War. The monument immortalized American statesman Daniel Webster. Webster was not an enslaver, but his support for the Fugitive Slave Law during the Compromise of 1850 forever scarred his legacy. When Massachusetts erected a monument of him in 1859, Boston abolitionists moved swiftly to remove it. This study indicates that the monument’s opponents were less concerned with the statue’s existence and more concerned with specific factors such as its location. The abolitionists argued that by placing a bronze monument on state property, the government was sanctioning Webster’s conservative position on slavery. Not only does this study provide an earlier example of our contemporary debate on monuments. It also investigates the politics of memory in a new light. It suggests that every step of the commemorative process – committees, funding, and statue placement – involves its own realm of politics and contestation

“The Statue Must Be Removed!”: Debates on Statues and the Memorialization of Daniel Webster and the Great Compromisers, 1852 – Present

“The Statue Must Be Removed!”: The Memorialization of Daniel Webster and the Great Northern Compromisers, 1853-Present Michael Larmann University of Montana, History Department, Doctoral Student 860-235-7881 | [email protected] The removal of statues has become a controversial topic in American society over the course of the past decade.Although statues of Confederate figures in the South have attracted the most attention in recent years, in the mid-nineteenth century, statues of Northern “compromisers”—those who sanctioned slavery rather than joining the abolitionist cause—also created controversy. Northern politicians such as Daniel Webster and President Millard Fillmore are two such figures who are historically notorious for supporting the Compromise of 1850, which postponed sectional hostilities, but also perpetuated chattel slavery and promoted slave catching in the United States for another decade. This research project analyzes the statues and memorialization of such Northern compromisers from the mid-nineteenth century up until today. It furthermore contributes to emerging scholarship on statues, nineteenth-century American history, and the creation of memory. Daniel Webster will serve as the focus of this project, since the erection of his statue in Boston, Massachusetts in 1859 started one of the first controversies in the United States about memorializing compromise. Through the use of memorial committee records, abolitionist newspapers, petitions, correspondence, broadsheets, and speeches, this project will analyze the controversy of memorializing Daniel Webster, the Massachusetts senator who infamously supported the Fugitive Slave Law in 1850. This project also analyzes how academics and the American public has since remembered Webster, Fillmore, and similar northern compromisers up until the present by looking at the erection of later statues and analyzing bibliographies. Popular culture sources that featured Daniel Webster’s image including theatre productions, movies, and non-academic books will help determine how the American public has remembered Webster since the nineteenth century, if they do at all. The final portion of this project discusses where historic actors such as Webster fit into today’s debates on memorializing controversial figures. The goal of this project is to understand how the American public has memorialized northern compromisers over time and where they sit with us today. Additionally, this research emphasizes the politics and power dimensions involved in building statues in the nineteenth century. The Webster statue in particular was the work of the private and wealthy Boston Brahmin elite class. A discussion about statues is also a story about the groups that erected them and the environments in which they are built. Therefore, this project also explains the processes and importance through which people engraved statues and memorials into the physical landscape and material environment of the American metropolis in the nineteenth century. This research on the Daniel Webster statue and the image of the Northern compromiser reveals that criticisms and debates about removing and building statues temporally go back to the mid-nineteenth century. This past decade in our nation’s history was not the first time that citizens have debated memorializing controversial individuals. Members of the American public were debating the meanings of memorialization and statues longer ago than previously believed

Gateways To Art: Understanding the visual arts

Tujuan Umum dari penulisan buku ini adalah membantu siswa belajar untuk menafsirkan seni dalam berbagai cara dan membantu siswa mengembangkan apa yang telah mereka ketahui. Buku ini dilengkapi pula dengan lebih dari 1000 ilustrasi dari seluruh dunia yang bisa ditemukan dalam kehidupan sehari-hari. Penyajiannya adalah pada bagian introduksi membahasa secara umum tentang seni, dilanjutkan dengan seni 2D & 3D, warna dan pencahayaan, lukisan, dkv, photography, patung, dll

In Vivo Fluorescence-mediated Tomography Imaging Demonstrates Atorvastatin-mediated Reduction of Lesion Macrophages in ApoE(-/-) Mice

Background: Macrophage recruitment into atherosclerotic plaques drives lesion progression, destabilization, and rupture. Chronic statin treatment reduces macrophage plaque content. Information on dynamics of macrophage recruitment would help assessing plaque vulnerability and guiding therapy. Techniques to image macrophage homing to vulnerable plaques in vivo are scarcely available. The authors tested if noninvasive fluorescence-mediated tomography (FMT) can assess plaque-stabilizing effects of short-term high-dosage atorvastatin. Methods: Macrophages from green-fluorescent-protein-transgenic mice were labeled with a near-infrared fluorescent dye and were injected IV in apolipoprotein E-deficient mice (n = 9) on Western diet 7 days after guidewire-injury of the carotid artery. FMT-scans, 2 and 7 days thereafter, quantified macrophage recruitment into carotid artery plaques. Atorvastatin was tested for macrophage adhesion, proliferation, and viability (n = 5 to 6) in vitro. Fourteen mice received atorvastatin or vehicle for 4 days after 16 weeks on Western diet. FMT assessed macrophage recruitment into aortic and innominate artery lesions. Means (+/- SD)% are reported. Results: Double-labeled macrophages were recruited into carotid artery lesions. FMT resolved fluorescence projecting on the injured carotid artery and detected a signal increase to 300% (+/- 191) after guidewire injury. Atorvastatin reduced macrophage adhesion to activated endothelial cells by 36% (+/- 19). In a clinically relevant proof-of-concept intervention, FMT-imaging detected that 4 days atorvastatin treatment reduced macrophage recruitment by 57% (+/- 8) indicating plaque stabilization. Immunohistochemistry confirmed reduced macrophage infiltration. Conclusions: FMT optical imaging proved its high potential for clinical applicability for tracking recruitment of near-infrared fluorescent-labeled macrophages to vulnerable plaques in vivo. FMT-based quantification of macrophage recruitment demonstrated rapid plaque stabilization by 4-day atorvastatin treatment in apolipoprotein E-deficient mice