Abstract 13393: Liraglutide Improves Myocardial Redox State in Humans by Regulating the Adipose Tissue-Derived Long-Chain Ceramides

Introduction: A notable reduction in major adverse cardiovascular events and cardiovascular mortality was observed in several cardiovascular studies via treatment with liraglutide, which have been suggested to be mediated through several mechanisms including inhibition of oxidative stress. Hypothesis: We hypothesised that treatment with liraglutide reduces oxidative stress via modulating circulating levels of long-chain ceramides. Methods: We measured vascular superoxide production using lucigenin-enhanced chemiluminescence and levels of circulating ceramides using LC-MS/MS in 633 participants of the Oxford Heart Vessels and Fat (OxHVF) cohort. We also measured 33 sphingolipid species (SPL) in plasma from 32 obese individuals (average BMI 33.5±2.5kg/m 2 at inclusion) participating in a randomized clinical trial (RCT) of low calorie diet and liraglutide. Results: We found a significant association between superoxide production by internal mammary arteries (IMA) and circulating levels of long-chain ceramides (C16:0, C17:0, C18:0, C18:1) (A-D) . In the RCT, all participants adhered to an 8-week low-calorie diet (800 kcal/day) (E) , during which they lost 9.9±6.0 kg of body weight exhibiting a significant reduction in BMI ( p <0.0001), which was paralleled by significant effects on the circulating levels of SPL (F) . Following this initial phase, the patients were randomised to liraglutide treatment (1.2 mg daily) or no treatment, for a period of 52 weeks. Liraglutide treatment differentially affected several SPL species compared to the control group despite no significant changes in BMI in any of the two groups (G-J) . Conclusions: In this study, we observed for the first time in human a regulatory effect of liraglutide on the circulating levels of long-chain ceramides that are shown to be associated with vascular oxidative stress suggesting a promising mechanistic link that justifies further exploration.

Single institutional experience of management of penetrating trauma chest

Chest trauma is now the second most common non-intentional traumatic injury. Chest trauma is associated with high mortality. Control of blood loss and stabilization of vital organs is of vital importance over diagnostic and therapeutic measures. Bleeding may arise from chest wall, intercostal or internal mammary arteries, great vessels, mediastinum, myocardium, lung parenchyma, diaphragm or abdomen. Modified early warning signs (MEWS) score of >9 on presentation have shown higher rate of mortality. Diagnostic modalities such as extended-focused assessment with sonography in trauma (eFAST) have been effective. The type of surgical approach alters according to the site of injury. We here presented our experience with six such patients. All the six patients involved in this study had penetrating trauma chest with various sharp weapons including dagger, ice pick, flag post. Time of presentation of all these patients were delayed due to ours being a tertiary centre. The patients were explored on the basis of eFAST findings, intercostal drainage, hemodynamics. Out of the six patients two patients succumbed and the patients who died also had high MEWS score. All the patients were approached surgically with respect to the type of injury sustained. Penetrating chest trauma present a challenging clinical situation which warrants early evaluation and intervention. The cases of chest trauma then be it blunt or penetrating should always be treated within the advanced trauma life support (ATLS) guidelines followed by the definitive management. Regardless of any penetrating object, the foreign body should be left in situ and only to be removed under vision. If in case the penetrating object has already been removed the operative intervention is decided on the amount of drainage. With blunt chest trauma, approximately 15% of the deaths result directly from intrathoracic injury, but with penetrating chest trauma, nearly 100% of the deaths result from intrathoracic injury. Hence, the operative exploration of the chest in penetrating chest trauma and should be done on emergent basis as the mechanism of injury, vital organ damage and hemodynamic status all equate to higher rate of mortality.

Impact of some intraoperative factors on wound infection in cardiac surgery

Relevanc. Surgical Site Infection (SSI) after open heart surgery is a significant problem in clinical, social, and economic aspect which causes the need to identification of the preferred procedures for successful prevention of the SSI.Objectives. To determine risk of the SSI in cardiac surgery depending on complexity of intervention, using of cardiopulmonary bypass (CBP) and use of both internal mammary arteries (IMA).Methods. Prospective observations study from 2010 to 2019 in cardiac surgery department of the Ural Institute of Cardiology, where in total 4993 open heart surgery procedures were consecutively performed. All SSI cases were recorded up to 90 days after surgery. The analysis was performed to identify risk of cardiopulmonary bypass (CPB), bilateral IMA grafting and combined procedures on the risk of the postoperative wound infection.Results. During the investigation period, total 220 cases of the SSI (4,5%) have been registered of the 4993 patients undergoing open heart surgery. It included 42 cases of deep sternal infection (0,9%) and 178 cases of superficial infection (3,6%). The main pathogen identified was Staphylococcus epidermidis (56,4%). During the hospital period, 151 cases (66,5%) of SSI have been detected, with the median time to detection of the complication 6 days. The relative mortality risk in deep sternal infection group was 4,4 times higher than in the group without SSI (HR 4,6, 95 % CI 1,5-13,9, p=0,003624). CABG increases the relative risk of SSI in compare with non-CABG procedures (OR 3,086169; 95%CI 1,281 – 7,437), while the complexity of the operation (combined versus isolated interventions) does not significantly increase the risk (OR 0.972283; 95% CI: 0.696 - 1.359). The incidence of SSI in the group of in situ BIMA grafting was 8.8%, significantly increasing the likelihood of the SSI in compare to those with SIMA (OR 2.167983, 95% CI 1.463 - 3.212; p =0,000057). CBP significantly increases the risk of postoperative wound infections (OR 1.523890, 95% CI 1.149 - 2.022, p = 0.001742).Conclusions. Refusal of cardiopulmonary bypass, simultaneous procedures and bilateral coronary artery bypass does not allow completely to avoid postoperative wound infections. Nevertheless, the technical features of the preparations and use of grafts, including skeletonization, prevention of coagulation and the preference for sequential composite CABG, can reduce the risk associated with the type of the open heart surgery.

Signature transcriptome analysis of stage specific atherosclerotic plaques of patients

Background: Inflammation plays an important role in all the stages of atherosclerotic plaque development. The current study aimed at assessing the altered expression of genes functioning in inflammation within the early stage (ES) and advanced stage (AS) atherosclerotic plaques obtained from patients undergoing coronary artery bypass grafting (CABG) surgery and identifying biomarker panel/s that may detect the status of plaque stages using peripheral blood samples. Methods: A section of ES and AS plaques and normal left internal mammary arteries (LIMA) were obtained from 8 patients undergoing the CABG surgery. Total RNA isolated was analysed for mRNA and miRNA expression profile by Affymetrix arrays. Significant number of mRNAs was found to be differentially expressed in ES and AS plaque tissues relative to LIMA. The pathway analysis of differentially expressed mRNAs in the two plaque stages was also performed using DAVID Bioinformatics Database. Results: The mRNAs were found to be involved in critical inflammatory processes such as Toll-like receptor signalling pathway and cytokine-cytokine receptor interaction. Few miRNAs targeting these mRNAs were also altered in the two plaque conditions. QRT-PCR results showed similar expression pattern of few of the mRNAs and miRNAs in peripheral blood of same patients relative to healthy controls. Conclusion: Changes in mRNA and miRNA expression associated with various inflammatory processes occur in different atherosclerotic stage plaques as well as peripheral blood. Detection of such variations in patients blood can be used as a possible prognostic tool to detect and/or predict the risk and stage of atherosclerosis.

Basement membrane collagen IV deficiency promotes abdominal aortic aneurysm formation

Abdominal aortic aneurysm (AAA) is a complex disease which is incompletely accounted for. Basement membrane (BM) Collagen IV (COL4A1/A2) is abundant in the artery wall, and several lines of evidence indicate a protective role of baseline COL4A1/A2 in AAA development. Using Col4a1/a2 hemizygous knockout mice (Col4a1/a2+/−, 129Svj background) we show that partial Col4a1/a2 deficiency augmented AAA formation. Although unchallenged aortas were morphometrically and biomechanically unaffected by genotype, explorative proteomic analyses of aortas revealed a clear reduction in BM components and contractile vascular smooth muscle cell (VSMC) proteins, suggesting a central effect of the BM in maintaining VSMCs in the contractile phenotype. These findings were translated to human arteries by showing that COL4A1/A2 correlated to BM proteins and VSMC markers in non-lesioned internal mammary arteries obtained from coronary artery bypass procedures. Moreover, in human AAA tissue, MYH11 (VSMC marker) was depleted in areas of reduced COL4 as assessed by immunohistochemistry. Finally, circulating COL4A1 degradation fragments correlated with AAA progression in the largest Danish AAA cohort, suggesting COL4A1/A2 proteolysis to be an important feature of AAA formation. In sum, we identify COL4A1/A2 as a critical regulator of VSMC phenotype and a protective factor in AAA formation.

Single-stage open repair of severe asymmetric pectus excavatum and mitral valve replacement in connective tissue disease

We present a 14-year-old boy with Loey–Dietz syndrome with severe mitral regurgitation, pectus excavatum and scoliosis. The Haller index was 25. The heart was displaced into the left hemithorax. The right inferior pulmonary vein was very close to the sternum and vertebral body. Single-stage surgery was performed. An osseo-myo-cutaneous pedicled flap was created by sterno-manubrial junction dislocation and rib resection with bilateral internal mammary arteries supplying the flap. Cardiopulmonary bypass and mitral valve replacement was performed. The defect was bridged with three straight plates. The flap was laid on top and anchored. Early outcome at three months was good.

External stenting of vein grafts in coronary artery bypass grating: interim results from a two centers prospective study

Background previous studies evaluating external stents for saphenous vein grafts (SVG) in CABG were limited to on-pump isolated CABG and single grafting technique with one external stent per patient. The objective of this prospective study was to evaluate the safety and the short-term performance of external stents in a heterogeneous group of patients who underwent on- and off-pump CABG, single and sequential grafting. Methods 102 patients undergoing CABG were enrolled in two centers. All patients received internal mammary artery to the left anterior descending artery and additional arterial and/or venous grafts. In each patient, at least one SVG was supported with an external stent. Grafts’ patency and SVG lumen uniformity were assessed using CT angiography at a pre-defined time window of 6–12 months post procedure. All patients were prospectively followed-up via phone call and/or visit every 6 months for Major Adverse Cardiac and Cerebrovascular Events. Results 51 patients (50%) underwent off-pump CABG and 23 patients (23%) were grafted with bilateral internal mammary arteries. Each patient received one or more SVG grafted in a sequential technique (44%) or as a single graft (56%). All SVG were externally stented in 84% of patients and in 16% (n = 16) one SVG was stented and one remained unsupported. At 6–12 months, patency rates of LIMA, RIMA, externally stented SVG and none-stented SVG were 100, 100, 98 and 87.5% respectively. 90% of the externally stented SVG had uniform lumen compared to 37% of the non-stented SVG. Clinical follow-up was completed for all patients with a mean duration of 20 months (range 6–54 months). During follow up period, one patient experienced myocardial infarction due to occlusion of the LIMA-LAD graft and one patient experienced a transient ischemic attack. Conclusions External stenting of SVG is feasible and safe in CABG setting which includes off pump CABG and sequential SVG grafting and associated with acceptable early patency rates. Trial registration Study was registered at ClinicalTrials.gov. NCT01860274 (initial release 20.05.2013).