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. (J Vasc Surg 2018;68:177S-87S.) Clinical Relevance: Despite the clinical success of large-diameter vascular grafts, synthetic grafts in small-diameter vessels (<6 mm) are rarely used because of poor patency rates, which limit their application in peripheral and coronary vascular bypass graft procedures. Hence, nonthrombogenic materials with good biocompatibility and favorable mechanical characteristics that mimic the compliance and strength of the native vessels are required. One promising concept is the use of the hydrogel bacterial nanocellulose designed in tubular shape

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.Publikationsfonds ML

Immunophenotyping of Monocyte Migration Markers and Therapeutic Effects of Selenium on IL-6 and IL-1β 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-1β 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

Timely extracorporeal membrane oxygenation assist reduces mortality after bypass surgery in patients with acute myocardial infarction

Background Patients with acute myocardial infarction (AMI) are at high risk when undergoing emergency coronary artery bypass graft (CABG)-surgery. Their outcome remains poor despite increased use of extracorporeal membrane oxygenation (ECMO). We investigated the impact of timing for perioperative ECMO-support in these patients. Methods In this retrospective double-center study, we evaluated 201 patients with AMI undergoing CABG, dividing them into the following groups: No-ECMO (n = 101), preoperative ECMO (pre-ECMO, n = 6), intraoperative ECMO (ECC-ECMO, n = 67), and postoperative ECMO (post-ECMO, n = 27). We evaluated the impact of ECMO timing on postoperative mortality, organ function, and length of stay, comparing these to predicted outcome using different risk-scores. Results Post-ECMO patients showed lowest 30-day-survival (40.7%), while earlier ECMO-start was associated with better outcome (50.7% in extracorporeal circulation [ECC]-ECMO and 66.7% in pre-ECMO patients). On admission, only pre-ECMO and ECC-ECMO patients showed higher surgery- and intensive-care-unit (ICU)-related risk-scores. In pre- and ECC-ECMO patients, the first significant increase in lactate-levels (>4 mmol/L) was observed preoperatively, while this occurred 1 hour postoperatively in post-ECMO patients. Bilirubin was increased in all patients, decreasing after 3 and 12 days in pre- and ECC-ECMO patients, respectively, but only after 18 days in post-ECMO patients. Multiple ICU risk-scores did not discriminate survival-probability correctly. Only the ECMO-related survival after veno-arterial-ECMO-score correctly predicted the significantly lower survival in post-ECMO patients. Conclusion Our study shows that timely ECMO-support is associated with earlier bilirubin-downtrend and higher survival in patients with AMI after CABG. Lactate-increase greater than 4 mmol/L seems to be a helpful threshold to trigger the timely onset of ECMO-therapy, providing better survival

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.Transformationsvertra

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

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 degrees 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(111)Indium-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 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