Jan Spillner

The intraoperative decrease of selenium is associated with the postoperative development of multiorgan dysfunction in cardiac surgical patients

Objective:The trace elements selenium, copper, and zinc are essential for maintaining the oxidative balance. A depletion of antioxidative trace elements has been observed in critically ill patients and is associated with the development of multiorgan dysfunction and an increased mortality. Cardiac surgery using cardiopulmonary bypass provokes ischemia-reperfusion-mediated oxidative stress. We hypothesized that an intraoperative decrease of circulating trace elements may be involved in this response. Design:Prospective observational clinical study. Setting:University hospital cardiothoracic operation theater and intensive care unit. Patients:Sixty patients (age 65 ± 14 yrs) undergoing cardiac surgery with the use of cardiopulmonary bypass. Measurements and Main Results:Whole blood concentrations of selenium, copper, and zinc were measured after induction of anesthesia and 1 hr after admission to the intensive care unit. All patients were separated in a priori defined subgroups according to the development of no organ failure, single organ failure, and ≥2 organ failures in the postoperative period. Results:Fifty patients exhibited a significant selenium deficiency already before surgery, whereas copper and zinc concentrations were within the reference range.In all patients, blood levels of selenium, copper, and zinc were significantly reduced after end of surgery when compared to preoperative values (selenium: 89.05 ± 12.65 to 70.84 ± 10.46 &mgr;g/L; zinc: 5.15 ± 0.68 to 4.19 ± 0.73 mg/L; copper: 0.86 ± 0.15 to 0.65 ± 0.14 mg/L; p < .001).During their intensive care unit stay, 17 patients were free from any organ failure, while 31 patients developed single-organ failure and 12 patients multiple organ failure.Multilogistic regression analysis showed that selenium concentrations at end of surgery were independently associated with the postoperative occurrence of multiorgan failure (p = .0026, odds ratio 0.8479, 95% confidence interval 0.7617 to 0.9440). Conclusions:Cardiac surgery using cardiopulmonary bypass resulted in a profound intraoperative decrease of whole blood levels of antioxidant trace elements. Low selenium concentrations at end of surgery were an independent predictor for the postoperative development of multiorgan failure.

Low stroke rate and few thrombo-embolic events after HeartMate II implantation under mild anticoagulation

OBJECTIVES Bleeding and thrombo-embolism are two of the most threatening adverse events associated with the use of continuous flow left ventricular assist devices (LVADs) in the treatment of severe heart failure. We analysed our LVAD patients treated with the HeartMate II (HM II) device by following a low anticoagulation regimen. METHODS Between 2008 and February 2011, we implanted 40 HM II LVADs in our institution. Intention to treat was bridge to transplant in 25, destination therapy in 9, bridge to candidacy in 5 cases and bridge to recovery in 1 case. Heparin was started only after 24 h postoperatively, and Phenprocumon (Phen) was started after removal of all chest drains. International normalized ratio (INR) target in the years 2008-2009 was 2.5, and 2.0-2.5 since 2010. Acetyl salicylic acid (ASA) was prescribed 50-100 mg/day only in patients <55 years or in case of severe atherosclerotic disease of the right coronary artery. All data were analysed consecutively concerning thrombo-embolic and bleeding events. RESULTS Fifty-two percent of the patients were in INTERMACS level 1 or 2 at the time of implantation. The mean age was 58 ± 11 years, and the mean days under LVAD was 241 days (maximum: 1052 days). The survival rate was 87.5% after 30 years and 75% in the long term. Early postoperatively, no strokes or thrombo-embolic events occurred. In the long term, two patients suffered from ischaemic strokes, but recovered well. In both of these index events, the INR was lasting below 1.4. One of these two patients developed pump thrombosis additionally. Only three patients (ASA + Phen) developed gastrointestinal bleeding (7.5%). Two patients were withdrawn from Phen + ASA because of multiple angiodysplasia. CONCLUSIONS Compared with the literature, even a mild anticoagulation protocol does not increase the risk of thrombotic events, but reduces bleeding events in the use of an HM II LVAD.

Selenium blood concentrations in patients undergoing elective cardiac surgery and receiving perioperative sodium selenite

OBJECTIVES We recently reported that cardiac surgical patients in our institution exhibited low selenium blood levels preoperatively, which were further aggravated during surgery and independently associated with the development of postoperative multiorgan failure. Low circulating selenium levels result in a decreased antioxidant capacity. Both can be treated effectively by sodium-selenite administration. Little is known about the kinetics of exogenously administered sodium-selenite during acute perioperative oxidative stress. The aim of this study was to assess the effects of perioperative high-dose sodium-selenite administration on selenium blood concentrations in cardiac surgical patients. METHODS One hundred four cardiac surgical patients were enrolled in this prospective observational trial. Patients received an intravenous bolus of 2000 μg selenium after an induction of anesthesia and 1000 μg selenium every day further during their intensive care unit (ICU) stay. Selenium blood levels were measured at regular intervals. RESULTS Preoperative sodium-selenite administration increased selenium blood concentrations to normal values on ICU admission, but failed to prevent a significant decrease of circulating selenium on the first postoperative day. During the further ICU stay, selenium blood levels were normalized by the administration strategy and did not exceed the German reference range. No acute selenium-specific side effects occurred. When matching the participating patients to a historical control group without sodium-selenite administration, the chosen strategy was associated with a decrease in SAPS II (23 ± 7 versus 29 ± 8, P = 0.005) and SOFA scores (4 ± 3 versus 7 ± 2, P = 0.007) on the first postoperative day, but was unable to improve the postoperative outcome in patients staying >1 d in ICU. CONCLUSIONS Despite preemptive high-dose sodium-selenite administration, cardiac surgical patients experienced a significant decrease in circulating selenium levels on the first postoperative day.

Fibrin Gel as Alternative Scaffold for Respiratory Tissue Engineering

Fibrin gel has proven a valuable scaffold for tissue engineering. Complex geometries can be produced by injection molding; it offers effective cell seeding and can be produced autologous. In order to evaluate its suitability for respiratory tissue engineering, we examined proliferation, functionality, and differentiation of respiratory epithelial cells on fibrin gel in comparison to culture on collagen-coated, microporous membranes. Respiratory epithelial cells formed a confluent layer by day 4, and proliferation showed no significant difference with respect to surface. Measurement of the transepithelial electrical resistance reflected the development of a confluent epithelial cell layer and the subsequent initiation of adequate ion-transfer processes. Appearance of ciliae could be detected at similar time points, and ciliary beating could be observed for cells on both surfaces. Histology and immunohistochemistry of cells grown on fibrin gel revealed the onset of adequate differentiation. As no significant differences in respiratory epithelial cells’ proliferation, function, and differentiation could be observed between cells grown on fibrin gel compared to cells on a collagen-coated, microporous surface, we concluded that fibrin gel might prove a suitable scaffold for respiratory tissue engineering and merits further investigation to overcome the limitations associated with scaffolds currently in use.

Modeling and simulation of the cardiovascular system: a review of applications, methods, and potentials / Modellierung und Simulation des Herz-Kreislauf-Systems: ein Überblick zu Anwendungen, Methoden und Perspektiven

Abstract Proper function of the cardiovascular system is indispensible to human survival. However, this system is dominated by complex interactions between different physiological processes and control mechanisms. A structured analysis and a mathematical description of this system can provide more insight, and a computer-based simulation of dynamic processes in the cardiovascular system could be applied in numerous tasks. This article gives a review of different approaches to cardio-circulatory modeling and discusses methodological aspects and fields of application for several classes of models. Zusammenfassung Die Funktion des Herz-Kreislauf-Systems ist eine wichtige Voraussetzung für das Überleben des Menschen. Dieses System ist jedoch bestimmt von komplexen Wechselwirkungen zwischen verschiedensten physiologischen Prozessen und Regelungsmechanismen. Eine strukturierte mathematische Beschreibung und ein dynamisches Simulationsmodell können helfen, das Herz-Kreislauf-System besser zu verstehen. Dieser Artikel bietet einen Überblick zu verschiedenen Ansätzen in der kardiovaskulären Modellbildung und vergleicht methodische Aspekte und Anwendungsgebiete der einzelnen Modellarten.

Tissue-Engineered Fibrin-Based Heart Valve with Bio-Inspired Textile Reinforcement

The mechanical properties of tissue-engineered heart valves still need to be improved to enable their implantation in the systemic circulation. The aim of this study is to develop a tissue-engineered valve for the aortic position - the BioTexValve - by exploiting a bio-inspired composite textile scaffold to confer native-like mechanical strength and anisotropy to the leaflets. This is achieved by multifilament fibers arranged similarly to the collagen bundles in the native aortic leaflet, fixed by a thin electrospun layer directly deposited on the pattern. The textile-based leaflets are positioned into a 3D mould where the components to form a fibrin gel containing human vascular smooth muscle cells are introduced. Upon fibrin polymerization, a complete valve is obtained. After 21 d of maturation by static and dynamic stimulation in a custom-made bioreactor, the valve shows excellent functionality under aortic pressure and flow conditions, as demonstrated by hydrodynamic tests performed according to ISO standards in a mock circulation system. The leaflets possess remarkable burst strength (1086 mmHg) while remaining pliable; pronounced extracellular matrix production is revealed by immunohistochemistry and biochemical assay. This study demonstrates the potential of bio-inspired textile-reinforcement for the fabrication of functional tissue-engineered heart valves for the aortic position.

Milrinone Relaxes Pulmonary Veins in Guinea Pigs and Humans

Introduction The phosphodiesterase-III inhibitor milrinone improves ventricular contractility, relaxes pulmonary arteries and reduces right ventricular afterload. Thus, it is used to treat heart failure and pulmonary hypertension (PH). However, its action on pulmonary veins (PVs) is not defined, although particularly PH due to left heart disease primarily affects the pulmonary venous bed. We examined milrinone-induced relaxation in PVs from guinea pigs (GPs) and humans. Material and Methods Precision-cut lung slices (PCLS) were prepared from GPs or from patients undergoing lobectomy. Milrinone-induced relaxation was studied by videomicroscopy in naïve PVs and in PVs pre-constricted with the ETA-receptor agonist BP0104. Baseline luminal area was defined as 100%. Intracellular cAMP was measured by ELISA and milrinone-induced changes of segmental vascular resistances were studied in the GP isolated perfused lung (IPL). Results In the IPL (GP), milrinone (10 µM) lowered the postcapillary resistance of pre-constricted vessels. In PCLS (GP), milrinone relaxed naïve and pre-constricted PVs (120%) and this relaxation was attenuated by inhibition of protein kinase G (KT 5823), adenyl cyclase (SQ 22536) and protein kinase A (KT 5720), but not by inhibition of NO-synthesis (L-NAME). In addition, milrinone-induced relaxation was dependent on the activation of KATP-, BKCa 2+- and Kv-channels. Human PVs also relaxed to milrinone (121%), however only if pre-constricted. Discussion Milrinone relaxes PVs from GPs and humans. In GPs, milrinone-induced relaxation is based on KATP-, BKCa 2+- and Kv-channel-activation and on cAMP/PKA/PKG. The relaxant properties of milrinone on PVs lead to reduced postcapillary resistance and hydrostatic pressures. Hence they alleviate pulmonary edema and suggest beneficial effects of milrinone in PH due to left heart disease.

EuroScore 2 for identification of patients for transapical aortic valve replacement - a single center retrospective in 206 patients

BackgroundOperative risk scoring algorithms identify patients with severe AS for transcatheter valve implantation in whom the anticipated operative mortality for conventional surgery would be considered prohibitive. We compared the three risk scores EuroScore 1 (LES), society of thoracic surgeons’ (STS) score and ACEF (age-creatinine-ejection fraction score) to the readjusted EuroScore 2 recently presented.MethodsWe reviewed all consecutive patients receiving either isolated conventional aortic valve replacement (cAVR) or transapical aortic valve implantation (TA-TAVI) in a two-year period (n = 206). 30-days mortality was considered as primary endpoint.ResultsTA-TAVI was performed in 76 patients, isolated cAVR in 130 patients. Overall mortality was 4.4% (TA-TAVI: 7.9%; cAVR: 2.3%). EuroScore 2 showed a good estimation for the entire population as well as within the subgroups: 4,02 ± 5,36% (TA-TAVI: 6.16 ± 7.14%, cAVR: 2.77 ± 3.42%). Predicted mortalities as assessed by LES were largely overestimated (TA-TAVI: 27.4 ± 20.9% cAVR: 10.6 ± 10.6%, sensitivity: 0.89, specificity: 0.71). STS predicted mortality was 6.3 ± 4.4% for TA-TAVI patients as to 3.2 ± 3.1% for cAVR patients (sens.: 0.22, spec.: 0.96) and ACEF predicted a mortality of 1.16 ± 0.36% for cAVR and 1.58 ± 0.59% for TA-TAVI patients (sens.: 0.78, spec.: 0.89).ConclusionThe newly refined EuroScore 2 showed a good correlation within the studied population. For the individual patient, new cut-offs will have to be defined to triage patients for TAVI procedure. A drawback for complex score systems such as EuroScore and STS is the lack of recalibration to smaller populations as encountered in even large single centers.

PAS-Port® clampless proximal anastomotic device for coronary bypass surgery in porcelain aorta.

OBJECTIVES The severely calcified so-called porcelain aorta is one of the most dangerous and challenging findings in patients requiring coronary bypass surgery. Several techniques and technologies have been invented to handle this potentially lethal disease. We report on our initial experience with the PAS-Port® automated proximal clampless anastomotic device (Cardica, Inc., Redwood City, CA, USA), especially focussing on these patients. METHODS PAS-Port® anastomoses (for saphenous vein grafts) were performed in 17 patients undergoing coronary artery bypass graft (CABG) surgery. Of these, eight presented with the entity of porcelain aorta. In two patients, the diagnosis was previously known, in six cases heavily calcified aortas prohibiting any clamp manoeuvre were incidentally found intra-operatively. The site of anastomosis was determined by palpation and in individual cases with epi-aortic echocardiography. Other indications for PAS-Port® were localised dissection, acute myocardial infarction and partial sternotomy. Multislice computed tomography (CT) was performed in every patient to evaluate graft and anastomoses patency and appearance. RESULTS All 25 PAS-Port® anastomoses were triggered successfully. Two patients developed neurological deficits (prolonged reversible ischaemic neurological deficits, (PRIND)), with use of cardiopulmonary bypass (CPB) being the major predisposing factor (p=0.02). Graft patency could be affirmed in all grafts by multislice CT in all patients. CONCLUSIONS PAS-Port® anastomoses can be performed quickly, easily and, above all, safely in conditions prohibiting aortic clamping. Short-term results are excellent. Clear visualisation of anastomoses using multislice CT is an important advantage of the PAS-Port® device.

A new approach to interventional atrioventricular valve therapy

OBJECTIVE Transcatheter replacement or repair of mitral valve regurgitation has proved demanding. We aimed for a new approach to anchor a biologic heart valve in the mitral position by inserting a valve-carrying hollow body into the left atrium. This approach was investigated in both a simulation and an animal model. METHODS After creating a mold representing the porcine left atrium from the pulmonary veins as far as the mitral valve, a nitinol skeleton was sutured onto interlaced yarns of polyvinylidene fluoride fitting the mold. The resulting device was equipped with a commercially available stentless valve (25 mm) and investigated in a simulator regarding basic functionality. Furthermore, the device was implanted in 8 female pigs through incision of the left atrium during extracorporeal circulation. Before implantation, artificial regurgitation was created by means of excision from the posterior mitral leaflet. Hemodynamic, echocardiographic, and radiologic examinations followed. For a postmortem examination, the entire heart and the lungs were excised. RESULTS We could demonstrate the functionality of the heart valve in a complex, collapsible, and self-expanding hollow body. The device adapted to the surrounding structures, leading to an exclusion of the left atrium. Sufficient treatment of mitral regurgitation was monitored hemodynamically and by means of echocardiographic analysis, although overall visualization remained difficult. Therefore in 4 animals computed tomographic scans were performed. Autopsy revealed proper positioning without major trauma to the surrounding structures. CONCLUSION Anchoring an additional heart valve in the atrioventricular position does not necessarily need to be performed in the heart valve structure itself. Placement of an additional valve in the mitral position is feasible through this approach.