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Revascularization via coronary artery bypass grafting (CABG) to treat cardiovascular disease is established as one of the most important lifesaving surgical techniques worldwide. But the shortage in functionally self-adaptive autologous arteries leads to circumstances where the clinical reality must deal with fighting pathologies coming from the mismatching biophysical functionality of more available venous grafts. Synthetic biomaterial-based CABG grafts did not make it to the market yet, what is mostly due to technical hurdles in matching biophysical properties to the complex demands of the CABG niche. But bacterial Nanocellulose (BNC) Hydrogels derived by growing biofilms hold a naturally integrative character in function-giving properties by its freedom in designing form and intrinsic fiber architecture. In this study we use this integral to combine impacts on the luminal fiber matrix, biomechanical properties and the reciprocal stimulation of microtopography and induced flow patterns, to investigate biomimetic and artificial designs on their bio-functional effects. Therefore, we produced tubular BNC-hydrogels at distinctive designs, characterized the structural and biomechanical properties and subjected them to in vitro endothelial colonization in bioreactor assisted perfusion cultivation. Results showed clearly improved functional properties and gave an indication of successfully realized stimulation by artery-typical helical flow patterns.

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Background: Patients with Coronavirus Disease (COVID-19) often develop severe acute respiratory distress syndrome (ARDS) requiring prolonged mechanical ventilation (MV), and venovenous extracorporeal membrane oxygenation (V-V ECMO).Mortality in COVID-19 patients on V-V ECMO was exceptionally high; therefore, whether survival can be ameliorated should be investigated. Methods: We collected data from 85 patients with severe ARDS who required ECMO support at the University Hospital Magdeburg from 2014 to 2021. The patients were divided into the COVID-19 group (52 patients) and the non-COVID-19 group (33 patients). Demographic and pre-, intra-, and post-ECMO data were retrospectively recorded. The parameters of mechanical ventilation, laboratory data before using ECMO, and during ECMO were compared. Results: There was a significant difference between the two groups regarding survival: 38.5% of COVID-19 patients and 63.6% of non-COVID-19 patients survived 60 days (p = 0.024). COVID-19 patients required V-V ECMO after 6.5 days of MV, while non-COVID-19 patients required V-V ECMO after 2.0 days of MV (p = 0.048). The COVID-19 group had a greater proportion of patients with ischemic heart disease (21.2% vs 3%, p = 0.019). The rates of most complications were comparable in both groups, whereas the COVID-19 group showed a significantly higher rate of cerebral bleeding (23.1 vs 6.1%, p = 0.039) and lung bacterial superinfection (53.8% vs 9.1%, p = <0.001). Conclusion: The higher 60-days mortality among patients with COVID-19 with severe ARDS was attributable to superinfection, a higher risk of intracerebral bleeding, and the pre-existing ischemic heart disease.

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Multivessel coronary artery disease (CAD) is characterized by underlying chronic vascular inflammation and occlusion in the coronary arteries, where these patients undergo coronary artery bypass grafting (CABG). Since post-cardiotomy inflammation is a well known phenomenon after CABG, attenuation of this inflammation is required to reduce perioperative morbidity and mortality. In this study, we aimed to phenotype circulating frequencies and intensities of monocyte subsets and monocyte migration markers, respectively, and to investigate the plasma level of inflammatory cytokines and chemokines between preoperative and postoperative CAD patients and later, to intervene the inflammation with sodium selenite. We found a higher amplitude of inflammation, postoperatively, in terms of CCR1high monocytes and significantly increased pro-inflammatory cytokines, IL-6, IL-8, and IL-1RA. Further, in vitro intervention with selenium displayed mitigating effects on the IL-6/STAT-3 axis of mononuclear cells derived from postoperative CAD patients. In addition, in vitro selenium intervention significantly reduced IL-1ß production as well as decreased cleaved caspase-1 (p20) activity by preoperative (when stimulated) as well as postoperative CAD mononuclear cells. Though TNF-α exhibited a positive correlation with blood troponin levels in postoperative CAD patients, there was no obvious effect of selenium on the TNF-α/NF-κB axis. In conclusion, anti-inflammatory selenium might be utilized to impede systemic inflammatory cytokine axes to circumvent aggravating atherosclerosis and further damage to the autologous bypass grafts during the post-surgical period.

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AIMS: Evidence suggests that a high-dose statin loading before a percutaneous coronary revascularization improves outcomes in patients receiving long-term statins. This study aimed to analyse the effects of such an additional statin therapy before surgical revascularization. METHODS AND RESULTS: This investigator-initiated, randomized, double-blind, and placebo-controlled trial was conducted from November 2012 to April 2019 at 14 centres in Germany. Adult patients (n = 2635) with a long-term statin treatment (≥30 days) who were scheduled for isolated coronary artery bypass grafting (CABG) were randomly assigned to receive a statin-loading therapy or placebo at 12 and 2 h prior to surgery using a web-based system. The primary outcome of major adverse cardiac and cerebrovascular events (MACCE) was a composite consisting of all-cause mortality, myocardial infarction (MI), and a cerebrovascular event occuring within 30 days after surgery. Key secondary endpoints included a composite of cardiac death and MI, myocardial injury, and death within 12 months. Non-statistically relevant differences were found in the modified intention-to-treat analysis (2406 patients; 1203 per group) between the statin (13.9%) and placebo groups (14.9%) for the primary outcome [odds ratio (OR) 0.93, 95% confidence interval (CI) 0.74-1.18; P = 0.562] or any of its individual components. Secondary endpoints including cardiac death and MI (12.1% vs. 13.5%; OR 0.88, 95% CI 0.69-1.12; P = 0.300), the area under the troponin T-release curve (median 0.398 vs. 0.394 ng/ml, P = 0.333), and death at 12 months (3.1% vs. 2.9%; P = 0.825) were comparable between treatment arms. CONCLUSION: Additional statin loading before CABG failed to reduce the rate of MACCE occuring within 30 days of surgery.

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BACKGROUND: At the onset of the coronavirus pandemic, concerns were raised about sufficiency of available intensive care resources. In many places, routine interventions were postponed and criteria for the allocation of scarce resources were formulated. In Germany, some hospitals were at times seriously burdened during the course of the pandemic. Intensive care units in particular experienced a shortage of resources, which may have led to a restriction of services and a stricter indication setting for resource-intensive measures such as extracorporeal membrane oxygenation (ECMO). The aim of this work is to provide an overview of how these pressures were managed at large ECMO centers in Germany. METHODS: One representative of each major ECMO referral center in Germany was invited to participate in an online survey in spring 2021. RESULTS: Of 34 invitations that were sent out, the survey was answered by 23 participants. In all centers, routine procedures were postponed during the pandemic. Half of the centers increased the number of beds on which ECMO procedures could be offered. Nevertheless, in one-third of the centers, the start of at least one ECMO support was delayed because of a feared resource shortage. In 17% of centers, at least one patient was denied ECMO that he or she would have most likely received under prepandemic conditions. CONCLUSION: The results of this online survey indicate that the experienced pressures and resource constraints led some centers to be cautious about ECMO indications.

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BACKGROUND: The aim of this Pilot study was to investigate the cardiac surgical residents' workload during different surgical teaching interventions and to compare their stress levels with other working time spent in the intensive care unit or normal ward. METHODS: The objective stress was assessed using two cardiac surgical residents' heart rate variability (HRV) both during surgical activities (32 selected teaching operations (coronary artery bypass graft n = 26 and transcatheter aortic valve implantation n = 6), and during non-surgical periods. Heart rate, time and frequency domains as well as non-linear parameters were analyzed using the Wilcoxon test. RESULTS: The parasympathetic activity was significantly reduced during the surgical phase, compared to the non-surgical phase: Mean RR (675.7 ms vs. 777.3 ms), RMSSD (23.1 ms vs. 34.0 ms) and pNN50 (4.7% vs. 10.6%). This indicates that the residents had a higher stress level during surgical activities in comparison to the non-surgical times. The evaluation of the Stress Index during the operations and outside the operating room (8.07 vs. 10.6) and the parasympathetic nervous system index (- 1.75 to - 0.91) as well as the sympathetic nervous system index (1.84 vs. 0.65) confirm the higher stress level during surgery. This can be seen too used the FFT Analysis with higher intraoperative LF/HF ratio (6.7 vs. 3.8). CONCLUSION: HRV proved to be a good, objective method of identifying stress among physicians both in and outside the operating room. Our results show that residents are exposed to high psychological workloads during surgical activities, especially as the operating surgeon.

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With the aging population, the demand for artificial small diameter vascular grafts is constantly increasing, as the availability of autologous grafts is limited due to vascular diseases. A confluent lining with endothelial cells is considered to be a cornerstone for long-term patency of artificial small diameter grafts. We use bacterial nanocellulose off-the-shelf grafts and describe a detailed methodology to study the ability of these grafts to re-colonize with endothelial cells in an in vitro bioreactor model. The viability of the constructs generated in this process was investigated using established cell culture and tissue engineering methods, which includes WST-1 proliferation assay, AcLDL uptake assay, lactate balancing and histological characterization. The data generated this straight forward methodology allow an initial assessment of the principal prospects of success in forming a stable endothelium in artificial vascular prostheses.

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BACKGROUND: Though laser guided extractions of cardiac implantable electronic devices leads have become a routine procedure, the severe complications are associated with a high mortality. Here, we report our single center experience using uniportal video-assisted thoracoscopy for laser lead extraction and compare it to stand-alone laser lead extraction. METHODS: The intraoperative data and postoperative clinical outcomes of patients undergoing laser lead extraction with concomitant thoracoscopy (N = 28) or without (N = 43) in our institution were analyzed retrospectively. RESULTS: Neither the median x-ray time (612.0 s for the thoracoscopy group vs. 495.5 s for the non-thoracoscopy group, p = 0.962), length of the operation (112.5 vs. 100.0 min, p = 0.676) or the median length of hospital stay (9.0 vs. 10.0 days, p = 0.990) differed significantly. The mean intensive care unit stay was longer for patients in the non-thoracoscopy group (0.8 vs. 2.5 days, p = 0.005). The 30-day-mortality in the thoracoscopy group was zero, whereas five patients died in the non-thoracoscopy group. Furthermore, four patients in the non-thoracoscopy group had encountered haemothorax, while none were observed in the thoracoscopy group (p = 0.148). CONCLUSIONS: The adoption of uniportal video-assisted thoracoscopy during laser-guided lead extraction of cardiac implantable electronic devices can be considered safe and does not lengthen the operating time or hospital stay. It might be useful in the detection of severe complications and, in experienced hands, possibly allow direct bleeding control.

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BACKGROUND: This study analysed the psychological and psycho-emotional stress in cardiac surgery. Using heart rate variability (HRV) analysis, it is possible to record intraoperative objective stress responses in surgeons. The aim of the study was to assess with the help of HRV parameters the postulated increased stress levels of cardiac surgeons in training compared to experienced senior cardiothoracic surgeons in exactly the same work situation in order to make qualification-differentiated statements about physiological stress during surgical interventions. METHODS: During surgical teaching procedures, long-term ECG data (n = 15 each) for two operating residents and their assisting senior physicians were recorded. Time and frequency domain HRV parameters were analysed. RESULTS: The time-related parasympathetic-dominated HRV parameters RMSSD (19.5 ms vs. 28.1 ms), NN50 (297.67 vs. 693.40), and cardiac interval mean RR (692.8 ms vs. 737.3 ms) indicate a higher stress level in the operating residents compared to the experienced surgeons. The higher stress index (11.61 vs. 8.86) confirms this. CONCLUSION: Compared to experienced surgeons, operating residents showed lower parasympathetic activity and higher stress levels during cardiac surgery training procedures.

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In this study, we contrast the impacts of surface coating bacterial nanocellulose small-diameter vascular grafts (BNC-SDVGs) with human albumin, fibronectin, or heparin-chitosan upon endothelialization with human saphenous vein endothelial cells (VEC) or endothelial progenitor cells (EPC) in vitro. In one scenario, coated grafts were cut into 2D circular patches for static colonization of a defined inner surface area; in another scenario, they were mounted on a customized bioreactor and subsequently perfused for cell seeding. We evaluated the colonization by emerging metabolic activity and the preservation of endothelial functionality by water soluble tetrazolium salts (WST-1), acetylated low-density lipoprotein (AcLDL) uptake assays, and immune fluorescence staining. Uncoated BNC scaffolds served as controls. The fibronectin coating significantly promoted adhesion and growth of VECs and EPCs, while albumin only promoted adhesion of VECs, but here, the cells were functionally impaired as indicated by missing AcLDL uptake. The heparin-chitosan coating led to significantly improved adhesion of EPCs, but not VECs. In summary, both fibronectin and heparin-chitosan coatings could beneficially impact the endothelialization of BNC-SDVGs and might therefore represent promising approaches to help improve the longevity and reduce the thrombogenicity of BNC-SDVGs in the future.

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The SARS-CoV-2 virus causing COVID-19 disease has emerged expeditiously in the world and has been declared pandemic since March 2020, by World Health Organization (WHO). The destructive effects of SARS-CoV-2 infection are increased among the patients with pre-existing chronic conditions and, in particular, this review focuses on patients with underlying cardiovascular complications. The expression pattern and potential functions of SARS-CoV-2 binding receptors and the attributes of SARS-CoV-2 virus tropism in a physio-pathological state of heart and blood vessel are precisely described. Of note, the atheroprotective role of ACE2 receptors is reviewed. A detailed description of the possible detrimental role of SARS-CoV-2 infection in terms of vascular leakage, including endothelial glycocalyx dysfunction and bradykinin 1 receptor stimulation is concisely stated. Furthermore, the potential molecular mechanisms underlying SARS-CoV-2 induced clot formation in association with host defense components, including activation of FXIIa, complements and platelets, endothelial dysfunction, immune cell responses with cytokine-mediated action are well elaborated. Moreover, a brief clinical update on patient with COVID-19 disease with underlying cardiovascular complications and those who had new onset of cardiovascular complications post-COVID-19 disease was also discussed. Taken together, this review provides an overview of the mechanistic aspects of SARS-CoV-2 induced devastating effects, in vital organs such as the heart and vessels.

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COPD and asthma are two distinct but sometimes overlapping diseases exhibiting varying degrees and types of inflammation on different stages of the disease. Although several biomarkers are defined to estimate the inflammatory endotype and stages in these diseases, there is still a need for new markers and potential therapeutic targets. We investigated the levels of a phytohormone, abscisic acid (ABA) and its receptor, LANCL2, in COPD patients and asthmatics. In addition, PPAR-γ that is activated by ABA in a ligand-binding domain-independent manner was also included in the study. In this study, we correlated ABA with COPD-propagating factors to define the possible role of ABA, in terms of immune regulation, inflammation, and disease stages. We collected blood from 101 COPD patients, 52 asthmatics, and 57 controls. Bronchoscopy was performed on five COPD patients and 29 controls. We employed (i) liquid chromatography-tandem mass spectrometry and HPLC to determine the ABA and indoleamine 2,3-dioxygenase levels, respectively; (ii) real-time PCR to quantify the gene expression of LANCL2 and PPAR-γ; (iii) Flow cytometry to quantify adipocytokines; and (iv) immunoturbidimetry and ELISA to measure CRP and cytokines, respectively. Finally, a multinomial regression model was used to predict the probability of using ABA as a biomarker. Blood ABA levels were significantly reduced in COPD patients and asthmatics compared to age- and gender-matched normal controls. However, PPAR-γ was elevated in COPD patients. Intriguingly, ABA was positively correlated with immune-regulatory factors and was negatively correlated with inflammatory markers, in COPD. Of note, ABA was increased in advanced COPD stages. We thereby conclude that ABA might be involved in regulation of COPD pathogenesis and might be regarded as a potential biomarker for COPD stages.

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Left ventricular rupture, also called atrioventricular disruption, remains a rare but lethal complication of mitral valve replacement. Available measures for preventing such a complication are limited to preservation of the posterior mitral leaflet and avoidance of overzealous decalcification of the annulus. Moreover, these strategies are not always feasible when annular calcifications prevent proper suture placement or when an abscess involves the mitral annulus. This report describes a surgical technique practiced in our clinic (Department of Cardiothoracic Surgery, University Hospital, Otto-von-Guericke-University, Magdeburg, Germany) that can be used in such high-risk patients to avoid left ventricular rupture.

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BACKGROUND: Treatment of functional mitral regurgitation using transcatheter techniques such as the Cardioband annuloplasty device (Edwards Lifesciences) has gained wide acceptance in the recent years. However, complications of such devices are rarely reported. METHODS: Here, we present a case series involving two patients with dislocation of the Cardioband device and discuss the surgical management. RESULTS: In the former the valve was re-repaired by surgical implantation of an annuloplasty ring, and in the latter the valve had to be replaced due to severe damage of the mitral valve annulus. Both patients had an uncomplicated course and were discharged to rehabilitation Center. CONCLUSION: Dislocation of the Cardioband devices can be successfully managed by surgical approaches. Depending on the extent of damage to the mitral valve annulus, the valve could be re-repaired or should be repalced.

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Closure of the left atrial appendage is a common procedure for patients with atrial fibrillation undergoing cardiac surgery. The technique of left atrial appendage occlusion (LAAO) by an extracardiac clip (AtriClip) is established as a reliable method. Acute coronary obstruction of the circumflex artery has already been described after minimally invasive LAAO. Here, we report a case of delayed circumflex artery obstruction after open-heart surgery. A patient who had mitral and tricuspid valve surgery in combination with AtriClip implantation suffered from myocardial infarction 24 h after clip implantation. Cardiac catheterization showed that the circumflex artery was obstructed on the level of the AtriClip device. The stenosis was treated by percutaneous coronary intervention with stent implantation. In conclusion, the surgeon should consider placing the AtriClip device slightly far away from the base of the left atrial appendage to avoid coronary obstruction.

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BACKGROUND: Scientific attempts to create the "ideal" small diameter vascular graft have been compared with the "search of the holy grail." Prosthetic material as expanded polytetrafluoroethylene or Dacron shows acceptable patency rates to large caliber vessels, while small diameter (< 6 mm) prosthetic conduits present unacceptably poor patency rates. Vascular tissue engineering represents a promising option to address this problem. MATERIAL AND METHODS: Thirty-two female Texel-sheep aged 6 months to 2 years underwent surgical common carotid artery (CCA) interposition using different tissue-engineered vascular substitutes. Explantation of the grafts was performed 12 (n = 12) and 36 (n = 20) weeks after surgery. Ultrasound was performed on postoperative day 1 and thereafter every 4 weeks to evaluate the graft patency. RESULTS: The average length of implanted substitutes was 10.3 ± 2.2 cm. Anesthesia and surgical procedure could be performed without major surgical complications in all cases.The grafts showed a systolic blood flow velocity (BFV) of 28.24 ± 13.5 cm/s, a diastolic BFV of 9.25 ± 4.53 cm/s, and a mean BFV of 17.85 ± 9.25 cm/s. Native vessels did not differ relevantly in hemodynamic measurements (systolic: 29.77 cm/s; diastolic: 7.99 cm/s ± 5.35; mean 15.87 ± 10.75). There was no incidence of neurologic complications or subsequent postoperative occlusion. Perioperative morbidity was low and implantation of conduits was generally well tolerated. CONCLUSION: This article aims to give a precise overview of in vivo experiments in sheep for the evaluation of small diameter vascular grafts performing CCA interposition, especially with regard to pitfalls and possible perioperative complications and to discuss advantages and disadvantages of this approach.

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Immune checkpoint molecules are the antigen-independent generator of secondary signals that aid in maintaining the homeostasis of the immune system. The programmed death ligand-1 (PD-L1)/PD-1 axis is one among the most extensively studied immune-inhibitory checkpoint molecules, which delivers a negative signal for T cell activation by binding to the PD-1 receptor. The general attributes of PD-L1's immune-suppressive qualities and novel mechanisms on the barrier functions of vascular endothelium to regulate blood vessel-related inflammatory diseases are concisely reviewed. Though targeting the PD-1/PD-L1 axis has received immense recognition-the Nobel Prize in clinical oncology was awarded in the year 2018 for this discovery-the use of therapeutic modulating strategies for the PD-L1/PD-1 pathway in chronic inflammatory blood vessel diseases is still limited to experimental models. However, studies using clinical specimens that support the role of PD-1 and PD-L1 in patients with underlying atherosclerosis are also detailed. Of note, delicate balances in the expression levels of PD-L1 that are needed to preserve T cell immunity and to curtail acute as well as chronic infections in underlying blood vessel diseases are discussed. A significant link exists between altered lipid and glucose metabolism in different cells and the expression of PD-1/PD-L1 molecules, and its possible implications on vascular inflammation are justified. This review summarizes the most recent insights concerning the role of the PD-L1/PD-1 axis in vascular inflammation and, in addition, provides an overview exploring the novel therapeutic approaches and challenges of manipulating these immune checkpoint proteins, PD-1 and PD-L1, for suppressing blood vessel inflammation.

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In this study, the hemocompatibility of tubes with an inner diameter of 5 mm made of polyvinyl chloride (PVC) and coated with different bioactive conjugates was compared to uncoated PVC tubes, latex tubes, and a stent for intravascular application that was placed inside the PVC tubes. Evaluation of hemocompatibility was done using an in vitro hemodynamic loop model that is recommended by the ISO standard 10993-4. The tubes were cut into segments of identical length and closed to form loops avoiding any gap at the splice, then filled with human blood and rotated in a water bath at 37 °C for 3 hours. Thereafter, the blood inside the tubes was collected for the analysis of whole blood cell count, hemolysis (free plasma hemoglobin), complement system (sC5b-9), coagulation system (fibrinopeptide A), and leukocyte activation (polymorphonuclear elastase, tumor necrosis factor and interleukin-6). Host cell activation was determined for platelet activation, leukocyte integrin status and monocyte platelet aggregates using flow cytometry. The effect of inaccurate loop closure was examined with x-ray microtomography and scanning electron microscopy, that showed thrombus formation at the splice. Latex tubes showed the strongest activation of both plasma and cellular components of the blood, indicating a poor hemocompatibility, followed by the stent group and uncoated PVC tubes. The coated PVC tubes did not show a significant decrease in platelet activation status, but showed an increased in complement and coagulation cascade compared to uncoated PVC tubes. The loop model itself did not lead to the activation of cells or soluble factors, and the hemolysis level was low. Therefore, the presented in vitro hemodynamic loop model avoids excessive activation of blood components by mechanical forces and serves as a method to investigate in vitro interactions between donor blood and vascular medical devices.

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OBJECTIVE: There is an increasing need for small diameter vascular grafts with superior host hemo- and cytocompatibilities, such as low activation of platelets and leukocytes. Therefore, we aimed to investigate whether the preparation of bacterial nanocellulose grafts with different inner surfaces has an impact on in vitro host cytocompatibility. METHODS: We have synthesized five different grafts in a bioreactor, namely open interface surface (OIS), inverted (INV), partially air dried (PAD), surface formed in air contact (SAC) and standard (STD) that were characterized by a different surface roughness. The grafts (length 55 mm, inner diameter 5 mm) were attached to heparinized polyvinyl chloride tubes, loaded with human blood and rotated at 37°C for 4 hours. Then, blood was analyzed for frequencies of cellular fractions, oxidative products, soluble complement and thrombin factors. The results were compared to clinically approved grafts made of polyethylene terephthalate and expanded polytetrafluoroethylene. Additionally, blood platelets were labelled with 111Indium-oxine to visualize the distribution of adherent platelets in the loop by scintigraphy. RESULTS: SAC nanocellulose grafts with the lowest surface roughness exhibited superior performance with <10% leukocyte and <50% thrombocyte loss in contrast to other grafts that exhibited >65% leukocyte and >90% thrombocyte loss. Of note, SAC nanocellulose grafts showed lowest radioactivity with scintigraphy analyses, indicating reduced platelet adhesion. Although the levels of reactive oxygen species and cell free DNA did not differ significantly, the levels of thrombin-antithrombin complexes were lowest in SAC grafts. However, all nanocellulose grafts exhibited enhanced complement activation. CONCLUSION: The systematic variation of the inner surfaces of BNC vascular grafts significantly improves biocompatibility. Especially, SAC grafts exhibited the lowest loss of platelets as well as leukocytes and additionally significantly diminished activation of the coagulation system. Further animal studies are needed to study in vivo biocompatibilities.

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