Integrated biophysical matching of bacterial nanocellulose coronary artery bypass grafts towards bioinspired artery typical functions.

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.

Immunophenotyping of Monocyte Migration Markers and Therapeutic Effects of Selenium on IL-6 and IL-1ß Cytokine Axes of Blood Mononuclear Cells in Preoperative and Postoperative Coronary Artery Disease Patients.

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.

Activation of the stress response among the cardiac surgical residents: comparison of teaching procedures and other (daily) medical activities.

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.

Bacterial Nanocellulose-Based Grafts for Cell Colonization Studies: An In Vitro Bioreactor Perfusion Model.

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.

Monitoring excimer laser-guided cardiac lead extractions by uniportal video-assisted thoracoscopy: A single center experience.

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.

The SARS-CoV-2/Receptor Axis in Heart and Blood Vessels: A Crisp Update on COVID-19 Disease with Cardiovascular Complications.

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.

Comparative Evaluation on Impacts of Fibronectin, Heparin-Chitosan, and Albumin Coating of Bacterial Nanocellulose Small-Diameter Vascular Grafts on Endothelialization In Vitro.

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.

Case series of late complications after transcatheter mitral annuloplasty using Cardioband and surgical treatment options.

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.

Experimental Studies for Small Diameter Grafts in an In Vivo Sheep Model-Techniques and Pitfalls.

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.

Left atrial appendage occlusion device causing coronary obstruction: A word of caution.

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.

Delicate Role of PD-L1/PD-1 Axis in Blood Vessel Inflammatory Diseases: Current Insight and Future Significance.

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.

An In Vitro Hemodynamic Loop Model to Investigate the Hemocytocompatibility and Host Cell Activation of Vascular Medical Devices.

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.

In vitro hemo- and cytocompatibility of bacterial nanocelluose small diameter vascular grafts: Impact of fabrication and surface characteristics.

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.

Surgical Management of Iatrogenic Left Ventricle Perforation by Chest Tube Insertion.

Chest tube thoracostomy is a standard procedure in every intensive care unit. Although it is regarded as a safe procedure in experienced hands, rare complications do occur. This report describes iatrogenic perforation of the left ventricle after placement of an intercostal catheter and the successful surgical management of this injury. Various operative situations that may arise in relation to iatrogenic perforation of the left ventricle are also discussed, as well as steps to manage this potentially life-threatening complication.

Late Onset Valve Dislocation of the Edwards Intuity Rapid-Deployment Bioprosthesis.

Over the last decade, aortic valve replacement with rapid-deployment biologic bioprostheses has become a common alternative to the use of mechanical or biologic stented valves for high-risk patients. A 63-year-old patient underwent uncomplicated valve replacement with the Edwards Intuity valve (Edwards Lifesciences, Irvine, CA). Two months postoperatively, the patient had progressive dyspnea. Echocardiography showed a dislocated aortic valve reaching into the left ventricular outflow tract and impairing the anterior mitral valve leaflet. Both valves were replaced by a conventional stented bioprosthesis. This case report describes the first case of valve migration for the Edwards Intuity Elite rapid-deployment aortic valve and discusses possible explanations.

Preoperative intraaortic balloon pump before urgent coronary bypass grafting.

Background Urgent or emergency coronary artery bypass grafting in patients with acute coronary syndrome is associated with increased morbidity and mortality. We investigated the effects of preoperative intraaortic balloon pump support in this high-risk patient cohort. Methods Our institutional database was retrospectively reviewed for patients with acute coronary syndrome and an urgent or emergency indication for coronary artery bypass from April 2010 to December 2016. Data of 1066 patients were analyzed. We assessed the impact of preoperative intraaortic balloon pump therapy on postoperative mortality and major adverse cardiovascular and cerebrovascular events, and performed propensity-score matching. Results Intraaortic balloon pump support was implemented in 223 (20.9%) patients: 55 (5.2%) preoperatively and 168 (15.8%) intra- or postoperatively. Overall hospital mortality was 8.8%. Patients with a preoperative intraaortic balloon pump had increased mortality (11/55, 20%) compared to controls ( p = 0.006). After propensity-score matching, all-cause mortality (20.0% vs. 18.2%, p = 0.834), cardiac mortality (18.2% vs. 14.5%, p = 0.651), and major adverse cardiovascular and cerebrovascular events (29.1% vs. 27.3%, p = 0.855) were comparable between groups. Conclusions Preoperative intraaortic balloon pump support does not confer any additional clinical benefit on patients undergoing coronary artery bypass grafting for acute coronary syndrome.

Patency and in vivo compatibility of bacterial nanocellulose grafts as small-diameter vascular substitute.

OBJECTIVE: Despite the clinical success of large-diameter vascular grafts, synthetic grafts in small-diameter vessels are of limited use because of their poor patency rates. Previous experiments of our group provided evidence for good biocompatibility of bacterial nanocellulose (BNC) as a small-vessel graft in the carotid artery in sheep. However, the patency rate of our first-generation tubes after 3 months was only 50%. To advance our concept, we now used modified second-generation tubes with diminished wall thickness and a smoother inner surface to reduce the thrombogenic potential. The aim was to investigate mechanical characteristics of modified second-generation BNC tubes, to evaluate in vivo performance and biocompatibility, and to analyze patency rates. METHODS: We replaced the right carotid artery of 23 sheep with second-generation BNC tubes. Compared with our first-generation tubes, tubes were modified with different surface properties and diminished wall thickness (inner diameter, 4.0-5.0 mm; wall thickness, 1.0-2.5 mm; length, 100 mm) to generate a smoother inner surface with reduced thrombogenic potential and a more porous outer zone, allowing easier cell immigration. RESULTS: At the end of the investigational period, BNC tubes were explanted and grafts were processed for histopathologic analysis. Histologic analysis revealed no acute signs of foreign body reaction such as immigration of giant cells or other acute inflammatory reaction and therefore provided evidence for good biocompatibility of the second-generation tubes. However, all grafts of the sheep without antiplatelet therapy were occluded after 9 months, whereas grafts in sheep receiving dual platelet inhibition showed a patency rate of 67% (six of nine grafts). Further modified grafts revealed a patency rate of 80% (four of five grafts remained open). CONCLUSIONS: Patency rates of the second-generation tubes could be substantially improved compared with our first-generation tubes. However, poor patency rates of tissue-engineered blood vessels still limit their use in clinical studies. Further efforts in terms of in vitro and in vivo studies are essential to improve grafts of BNC.

cfDNA correlates with endothelial damage after cardiac surgery with prolonged cardiopulmonary bypass and amplifies NETosis in an intracellular TLR9-independent manner.

Cardiopulmonary bypass (CPB) provokes inflammation culminating in organ dysfunction and increased mortality. Recently, neutrophil extracellular traps (NETs) have been found to be involved in a variety of cardiovascular diseases promoting tissue and organ injury. Here, we aimed to elaborate the proinflammatory potential of circulating cell-free (cf)DNA in patients undergoing cardiac surgery with CPB. Plasma was collected pre- and postoperatively as well as at d1, d3, d5 and d8 after surgery. At d1, we found circulating cfDNA levels to be significantly increased in patients with prolonged CPB duration (>100 min) when compared to those with shorter CPB times (CPB < 100 min). Increased CPB duration yielded in higher levels of circulating mitochondrial (mt)DNA, soluble thrombomodulin (sCD141) and ICAM-1, reflecting endothelial damage. Positive correlation between cfDNA and sCD141 was demonstrated at all time points. Plasma and cfDNA from patients with CPB > 100 min induced NETs release by neutrophils from healthy donors which was not suppressed by inhibitors of intracellular toll-like receptor (TLR)9. DNA binding to neutrophils' surface (s)TLR9 has been evidenced. Altogether, we demonstrate that elevated plasma cfDNA might be useful to assess CPB-mediated detrimental effects, including endothelial damage, in cardiac surgical patients with prolonged CPB duration. cfDNA-triggered NETosis is independent of classical TLR9 signaling.