The effect of perioperative hemadsorption in patients operated for acute infective endocarditis-A randomized controlled study.

Patients operated for infective endocarditis (IE) are at high risk of developing an excessive systemic hyperinflammatory state, resulting in systemic inflammatory response syndrome and septic shock. Hemoadsorption (HA) by cytokine adsorbers has been successfully applied to remove inflammatory mediators. This randomized controlled trial investigates the effect of perioperative HA therapy on inflammatory parameters and hemodynamic status in patients operated for IE. A total of 20 patients were randomly assigned to either HA therapy or the control group. HA therapy was initiated intraoperatively and continued for 24 hours postoperatively. Cytokine levels (IL-6, IL-1b, TNF-α), leukocytes, C-reactive protein (CRP), and Procalcitonin (PCT) as well as catecholamine support, and volume requirement were compared between both groups. Operative procedures included aortic (n = 7), mitral (n = 6), and multiple valve surgery (n = 7). All patients survived to discharge. No significant differences concerning median cytokine levels (IL-6 and TNF-α) were observed between both groups. CRP and PCT baseline levels were significantly higher in the HA group (59.5 vs. 26.3 mg/dL, P = .029 and 0.17 vs. 0.05 µg/L, P = .015) equalizing after surgery. Patients in the HA group required significantly higher doses of vasopressors (0.093 vs. 0.025 µg/kg/min norepinephrine, P = .029) at 12 hours postoperatively as well as significantly more overall volume replacement (7217 vs. 4185 mL at 12 hours, P = .015; 12 021 vs. 4850 mL at 48 hours, P = .015). HA therapy did neither result in a reduction of inflammatory parameters nor result in an improvement of hemodynamic parameters in patients operated for IE. For a more targeted use of HA therapy, appropriate selection criteria are required.

Development of a bioreactor system for pre-endothelialized cardiac patch generation with enhanced viscoelastic properties by combined collagen I compression and stromal cell culture.

Treatment of terminal heart failure still poses a significant clinical problem. Cardiac tissue engineering could offer autologous solutions for the replacement of nonfunctional myocardial tissue. So far, soft matrix construction and missing large-scale prevascularization prevented the application of sizeable cardiac repair patches. We developed a novel bioreactor system for semi-automatic compression of a collagen I hydrogel applying 16 times higher pressure than in previous studies. Resistance towards compression stress was investigated for multiple cardiac-related cell types. For scaffold prevascuarization, a tubular cavity was imprinted during the compaction process. Primary cardiac-derived endothelial cells (ECs) were isolated from human left atrial appendages (HLAAs) and characterized by fluorescence-activated cell sorting (FACS) and immunocytology. EC were then seeded into the preformed channel with dermal fibroblasts as interstitial cell component of the fully cellularized patch. After 8 days of constant perfusion culture within the same bioreactor, scaffold dynamic modulus and cell viability were analyzed. Endothelial proliferation and vessel maturation were examined by immunohistochemistry and transmission electron microscopy. Our design allowed for scaffold production and dynamic culture in a one-stop-shop model. Enhanced compression and cell-mediated matrix remodeling induced a significant increase in scaffold stiffness while ensuring excellent cell survival. For the first time, we could isolate HLAA-derived EC with proliferative potential. ECs within the central channel proliferated during flow culture, continuously expressing endothelial markers (CD31) and displaying basal membrane synthesis (collagen IV, ultrastructural analysis). After 7 days of culture, a complete endothelial monolayer could be observed. Covering cells aligned themselves in flow direction and developed mature cell-cell contacts.

Turning Things Around: The Role of Prone Positioning in the Management of Acute Respiratory Failure After Cardiac Surgery.

OBJECTIVES: The aim of this study was to determine the benefit of prone positioning (PP) in patients developing acute respiratory failure (ARF) after cardiac surgery. DESIGN: A retrospective analysis. SETTING: Review of the institutional database between October 2016 and October 2018 revealed 24 patients who underwent PP for the treatment of ARF after cardiac surgery. PARTICIPANTS: The authors found 24 patients who underwent PP for the treatment of ARF after cardiac surgery. This included 10 patients who required extracorporeal membrane oxygenation (ECMO) therapy. Among them, 6 patients with simultaneous PP and ECMO therapy. INTERVENTIONS: Data were collected at the time of PP, 6 hours after PP, at the end of PP, and 6 hours after return to supine position (SP). MEASUREMENTS AND MAIN RESULTS: The median duration of postoperative mechanical ventilation was 281 hours (183-528 hours). Prone positioning was carried out on the fourth postoperative day (POD), with a total of 5 patients undergoing PP within 24 hours following surgery. The median duration of PP before return to SP was 12 hours (12-16 hours), with the maximal duration of PP being 22 hours in this cohort. The authors observed an increase in Horowitz index (HI) at the end of PP (p < 0.001) as well as 6 hours after supine positioning. In the subgroup of patients who underwent PP on ECMO (v-a ECLS = 3, v-v ECMO = 3), a significant reduction of ECMO support was achieved from 3.0 (2.2-5.6) liters/min to 2.5 (2.0-4.6) liters/min (p = 0.023). No adverse events occurred during the positioning of the patients. CONCLUSIONS: Prone positioning can be considered for the treatment of ARF after cardiac surgery to improve short-term respiratory conditions and possibly facilitate ECMO weaning.

Ischemia time impacts on respiratory chain functions and Ca2+-handling of cardiac subsarcolemmal mitochondria subjected to ischemia reperfusion injury.

BACKGROUND: Mitochondrial impairment can result from myocardial ischemia reperfusion injury (IR). Despite cardioplegic arrest, IR-associated cardiodepression is a major problem in heart surgery. We determined the effect of increasing ischemia time on the respiratory chain (RC) function, the inner membrane polarization and Ca2+ homeostasis of rat cardiac subsarcolemmal mitochondria (SSM). METHODS: Wistar rat hearts were divided into 4 groups of stop-flow induced warm global IR using a pressure-controlled Langendorff system: 0, 15, 30 and 40 min of ischemia with 30 min of reperfusion, respectively. Myocardial contractility was determined from left ventricular pressure records (dP/dt, dPmax) with an intraventricular balloon. Following reperfusion, SSM were isolated and analyzed regarding electron transport chain (ETC) coupling by polarography (Clark-Type electrode), membrane polarization (JC1 fluorescence) and Ca2+-handling in terms of Ca2+-induced swelling and Ca2+-uptake/release (Calcium Green-5 N® fluorescence). RESULTS: LV contractility and systolic pressure during reperfusion were impaired by increasing ischemic times. Ischemia reduced ETC oxygen consumption in IR40/30 compared to IR0/30 at complex I-V (8.1 ± 1.2 vs. 18.2 ± 2.0 nmol/min) and II-IV/V (16.4 ± 2.6/14.8 ± 2.3 vs. 2.3 ± 0.6 nmol/min) in state 3 respiration (p < 0.01). Relative membrane potential revealed a distinct hyperpolarization in IR30/30 and IR40/30 (171.5 ± 17.4% and 170.9 ± 13.5%) compared to IR0/30 (p < 0.01), wearing off swiftly after CCCP-induced uncoupling. Excess mitochondrial permeability transition pore (mPTP)-gated Ca2+-induced swelling was recorded in all groups and was most pronounced in IR40/30. Pyruvate addition for mPTP blocking strongly reduced SSM swelling in IR40/30 (relative AUC, ± pyruvate; IR0/30: 1.00 vs. 0.61, IR15/30: 1.68 vs. 1.00, IR30/30: 1.42 vs. 0.75, IR40/30: 1.97 vs. 0.85; p < 0.01). Ca2+-uptake remained unaffected by previous IR. Though Ca2+-release was delayed for ≥30 min of ischemia (p < 0.01), Ca2+ retention was highest in IR15/30 (RFU; IR0/30: 6.3 ± 3.6, IR 15/30 42.9 ± 5.0, IR30/30 15.9 ± 3.8, IR40/30 11.5 ± 6.6; p ≤ 0.01 for IR15/30 against all other groups). CONCLUSIONS: Ischemia prolongation in IR injury gradually impaired SSM in terms of respiratory chain function and Ca2+-homeostasis. Membrane hyperpolarization appears to be responsible for impaired Ca2+-cycling and ETC function. Ischemia time should be considered an important factor influencing IR experimental data on subsarcolemmal mitochondria. Periods of warm global ischemia should be minimized during cardiac surgery to avoid excessive damage to SSMs.

Minimally invasive versus conventional extracorporeal circulation circuits in patients undergoing coronary artery bypass surgery: a propensity-matched analysis.

OBJECTIVES: Minimally invasive extracorporeal circulation circuits provide several advantages compared to conventional extracorporeal circulation circuits. We compared the results of a minimally invasive extracorporeal circulation system with those of conventional extracorporeal circulation system, in patients undergoing isolated coronary artery bypass grafting. METHODS: We identified 753 consecutive patients who underwent coronary artery bypass grafting at our centre between October 2014 and September 2016. These patients were divided into two groups: a minimally invasive extracorporeal circulation group (M, n = 229) and a conventional extracorporeal circulation group (C, n = 524). Baseline parameters, details of cardiac surgery as well as postoperative complications and outcomes were compared by means of a propensity-matched analysis of 180 matched pairs. RESULTS: The median EuroSCORE II was 1.3%. Transfusion requirement of packed red blood cells (p = 0.002) was lower in Group M compared to conventional extracorporeal circulation systems. There were no differences in hospital mortality or in rates of adverse events between the matched groups. Total in-hospital mortality of the cohort was 1.7%. CONCLUSION: The use of minimally invasive extracorporeal circulation is associated with a significantly lower use of blood products after isolated coronary revascularisation. There were no differences concerning duration of surgery, complication rates and mortality between the groups. Therefore, the application of minimally invasive extracorporeal circulation systems should be considered as preferred technique in isolated coronary artery bypass grafting procedures.

Recurrence of Spontaneous Pneumothorax Is Not Associated with Allegedly Risk-Prone Lifestyle Conduct.

PURPOSE: Spontaneous pneumothorax (PNTX) is a common disease frequently operated at specialized thoracic surgery units. Videothoracoscopic surgery (VATS) has become the standard for treatment and recurrence prevention. While there is broad consensus regarding indications and techniques of PNTX surgery, postoperative risks and consecutive patient behavioral advice have not been sufficiently elucidated. METHODS: Single-center cohort analysis of 641 patients operated for primary PNTX by VATS over 10 years. Putatively recurrence-prone lifestyle activities (smoking status, flying habits, and scuba diving) and actual occurrence of recurrences were correlated. RESULTS: Follow-up rate was 46% (279/607 patients). Mean time interval between primary operation and follow-up was 61 (range: 5-177) months. In 10 patients (3.6%), a PNTX recurrence was observed. Regarding postoperative risk behavior reported at follow-up, 28% of patients were active smokers (15 ± 7 cigarettes/day), 59% traveled by plane repeatedly, and only two patients did scuba diving (0.7%). Low body-mass-index was associated with an increase in PNTX recurrence, whereas smoking, flying, and scuba diving could not be identified as risk factors. CONCLUSION: In our study, none of the supposed "classic" lifestyle-associated risk factors for PNTX recurrence after VATS proved to be a significant threat. Postoperative patient behavior might not be constrained by overcautious medical advice.

Cardiac Surgery is Safe in Female Patients with a History of Breast Cancer.

PURPOSE: In cardiac surgery candidates, a concomitant history of breast cancer suggests adverse outcomes. The possibility of internal mammary artery (IMA) utilization and its patency rate is frequently discussed. Secondary, blood loss and wound related infections might be important issues. However, publications focusing on these issues are limited. METHODS: We analyzed 32 patients with previously treated breast cancer undergoing cardiac bypass (CABG) and combined CABG surgery matched to 99 control subjects in a retrospective cohort study. Patients were analyzed regarding IMA utilization, blood loss and substitution and frequent perioperative complications as well as long-term mortality. RESULTS: No significant differences between groups were observed regarding duration of surgery, IMA-utilization, incidence of infections and postoperative complications or mortality. A pronounced decline of hemoglobin/hematocrit was evident within the first 6 postoperative hours (3.3 ± 1.8 vs. 2.5 ± 1.8 mg/dl; p = 0.03) in breast cancer patients not related to an increased drainage loss but associated with an increase of international normalized ratio (INR) (0.39 ± 0.16 vs. 0.29 ± 0.24; p <0.01). CONCLUSION: In breast cancer patients, CABG and combined CABG procedures can safely be performed with comparable short- and long-term results.

Impact of levosimendan and ischaemia-reperfusion injury on myocardial subsarcolemmal mitochondrial respiratory chain, mitochondrial membrane potential, Ca2+ cycling and ATP synthesis.

OBJECTIVES: Levosimendan (LS) is increasingly used in case of myocardial failure after cardiac surgery. The impact of LS on myocardial mitochondrial functions, such as respiratory chain function (RCF), mitochondrial membrane potential (ΔΨm), Ca(2+) handling, mitochondrial permeability transition pore (mPTP) opening and ATP during ongoing ischaemia/reperfusion (IR) injury, is not well understood. Depending on LS, I/R injury or the combination of both, we analysed myocardial functions in a retrograde Langendorff-model followed by the analysis of subsarcolemmal mitochondrial (SSM) functions. METHODS: Rat hearts were divided into four study groups; two were subjected to 30 min of perfusion without (control) or with the application of 1.4 µmol/20 min LS (Levo). Experiments were repeated with hearts being subjected to 40 min of normothermic stop-flow ischaemia and 30 min of reperfusion without (IR) or with LS application (Levo-IR). Systolic left ventricular pressure (LVPsys), left ventricular contractility (LVdp/dtmax) and coronary flow were determined. SSM were analysed regarding RCF, ΔΨm, ATP, and Ca(2+) retention capacity (CRC), Ca(2+)-induced swelling and Ca(2+) fluxes after (re)perfusion. RESULTS: I/R injury suppressed LVdp/dtmax (1381 ± 927 vs 2464 ± 913 mmHg/s; P = 0.01 at 30 min (re-)perfusion time). IR revealed complex I-V state3 (19.1 ± 7.4 vs 27.6 ± 11.0 nmolO2/min; P < 0.044) and II-V state3 (20.6 ± 6.8 vs 37.3 ± 9.10 molO2/min; P < 0.0001) suppression and Levo limited I-V (14.8 ± 11.1 vs 27.6 ± 11.0 nmolO2/min; P < 0.001) and II-V (24.1 ± 6.4 vs 37.3 ± 9.10 molO2/min; P < 0.0001) function. After energizing, ΔΨm hypopolarization was observed in Levo (0.76 ± 0.04 vs 0.84 ± 0.04; P = 0.02), IR (0.75 ± 0.06 vs 0.84 ± 0.04; P = 0.007) and Levo-IR (0.75 ± 0.06 vs 0.06 ± 0.04; P = 0.01). IR (AUC: 626 vs 292; P = 0.023) and Levo-IR (AUC: 683 vs 292, P = 0.003) increased Ca(2+)-induced mPTP-opening susceptibility. CRC declined in IR (6.4 ± 2.1 vs 10.5 ± 2.6; P = 0.04) or Levo (6.5 ± 2.0 vs 10.5 ± 2.6; P = 0.023). Ca(2+) uptake was delayed in IR and Levo-IR without LS impact (P < 0.0001). Ca(2+) liberation was increased in Levo-IR. ATP synthesis was reduced in Levo (0.49 ± 0.14 vs 0.74 ± 0.14; P = 0.002) and Levo-I/R (0.34 ± 0.18 vs 0.74 ± 0.14; P < 0.002). CONCLUSION: LS limited RCF at complex IV and V with ΔΨm hypopolarization suggesting a specific [Formula: see text]-dependent pathway. Ca(2+) redistribution from SSM by LS during I/R injury possibly prevents from Ca(2+) overload due to mPTP flickering. LS-induced mPTP flickering did not promote permanent Ca(2+)-induced mPTP opening. LS-dependent inhibition of ATP generation presumably resulted from complex IV and V limitations and lowered ΔΨm. However, a resulting impact of limited ATP synthesis on myocardial recovery remains arguable.

Degree of Carotid Artery Stenosis in Neurologically Asymptomatic Cardiac Surgical Patients Suffering from Perioperative Stroke: Results of an Observational Study.

Background Postoperative stroke in cardiac surgical patients remains a serious adverse outcome. Methods A total of 2,784 consecutively operated cardiac surgical patients without preoperative neurologic impairment were analyzed retrospectively with regard to impact of preoperative carotid stenosis on the incidence of postprocedural new onset of stroke. Therefore, all analyzed patients were assigned to four groups depending on preoperative degree of carotid artery stenosis detected by carotid duplex sonography (group I: < 50%, group II: 50-75%, group III: 76-89%, and group IV: > 90%). Results All pre-, intra-, and postoperative risk factors for neurological disorders were comparable throughout the cohort. Of the 2,784 patients, 65 (2.3%) met the inclusion criteria (preoperatively neurologically asymptomatic status, preoperatively carotid duplex ultrasonography study not older than 6 months, heart surgery with extracorporeal circulation, stroke until 48 hours after operation). Of the 65 patients who met the inclusion criteria, 43 (66.2%) were in group I, 11 (16.9%) in group II, 5 (7.7%) in group III, and 6 (9.2%) in group IV (p = 0.175). The overall incidence of an ipsilateral stroke relating to the carotid stenosis was 38 (1.4%) patients. Of these, 27 (71.1%) patients were in group I, 6 (15.8%) patients in group II, 2 (5.3%) patients in group III, and 3 (7.9%) patients in group IV (p = 0.568). Conclusion This observational study demonstrates that the degree of carotid stenosis in neurologically asymptomatic cardiac surgical patients is not able to predict the probability of perioperative stroke. Until further results from prospective randomized trials with neurologically asymptomatic cardiac surgical patients are presented, a cautious attitude for concomitant carotid endarterectomy is still justified.

Water-based chitosan/melamine polyphosphate multilayer nanocoating that extinguishes fire on polyester-cotton fabric.

Polyester-cotton (PECO) blends are widely used in the textile industry because they combine the softness of cotton and the strength and durability of polyester. Unfortunately, both fiber types share the disadvantage of being flammable. The layer-by-layer coating technique was used to deposit a highly effective flame retardant (melamine polyphosphate) from water onto polyester-cotton fabric. Soluble melamine and sodium hexametaphosphate form this water-insoluble flame retardant during the coating procedure. This unique nanocoating imparts self-extinguishing properties to PECO with only 12% relative coating weight. Vertical flame testing, pyrolysis combustion flow calorimetry (PCFC), thermogravimetric analysis (TGA), and scanning electron microscopy were used to evaluate the quality of the coating as well as its flame retardant performance. A combination of both condensed and gas-phase activity appears to be the reason for this effective flame retardancy. Degradation pathways of both cotton and polyester are affected by the applied coating, as shown by PCFC and TGA. Use of environmentally benign and non-toxic chemicals, and the ease of layer-by-layer deposition, making this coating an industrially feasible alternative to render polyester-cotton fabric self-extinguishing.

Different duration strategies of perioperative antibiotic prophylaxis in adult patients undergoing cardiac surgery: an observational study.

BACKGROUND: All international guidelines recommend perioperative antibiotic prophylaxis (PAB) should be routinely administered to patients undergoing cardiac surgery. However, the duration of PAB is heterogeneous and controversial. METHODS: Between 01.01.2011 and 31.12.2011, 1096 consecutive cardiac surgery patients were assigned to one of two groups receiving PAB with a second-generation cephalosporin for either 56 h (group I) or 32 h (group II). Patients' characteristics, intraoperative data, and the in-hospital follow-up were analysed. Primary endpoint was the incidence of surgical site infection (deep and superficial sternal wound-, and vein harvesting site infection; DSWI/SSWI/VHSI). Secondary endpoints were the incidence of respiratory-, and urinary tract infection, as well as the mortality rate. RESULTS: 615/1096 patients (56,1%) were enrolled (group I: n = 283 versus group II: n = 332). There were no significant differences with regard to patient characteristics, comorbidities, and procedure-related variables. No statistically significant differences were demonstrated concerning primary and secondary endpoints. The incidence of DSWI/SSWI/VHSI were 4/283 (1,4%), 5/283 (1,7%), and 1/283 (0,3%) in group I versus 6/332 (1,8%), 9/332 (2,7%), and 3/332 (0,9%) in group II (p = 0,76/0,59/0,63). In univariate analyses female gender, age, peripheral arterial obstructive disease, operating-time, ICU-duration, transfusion, and respiratory insufficiency were determinants for nosocomial infections (all ≤ 0,05). Subgroup analyses of these high-risk patients did not show any differences between the two regimes (all ≥ 0,05). CONCLUSIONS: Reducing the duration of PAB from 56 h to 32 h in adult cardiac surgery patients was not associated with an increase of nosocomial infection rate, but contributes to reduce antibiotic resistance and health care costs.

Substrate- and cell contact-dependent inhibitor affinity of human organic cation transporter 2: studies with two classical organic cation substrates and the novel substrate cd2+.

Polyspecific organic cation transporter Oct2 from rat (gene Slc22A2) has been previously shown to transport Cs(+). Here we report that human OCT2 (hOCT2) is able to transport Cd(2+) showing substrate saturation with a Michaelis-Menten constant (Km) of 54 ± 5.8 µM. Uptake of Cd(2+) by hOCT2 was inhibited by typical hOCT2 ligands (unlabeled substrates and inhibitors), and the rate of uptake was decreased by a point mutation in a substrate binding domain of hOCT2. Incubation of hOCT2 overexpressing human embryonic kidney 293 cells (HEK-hOCT2-C) or rat renal proximal tubule cells expressing rOct2 (NRK-52E-C) with Cd(2+) resulted in an increased level of apoptosis that was reduced by OCT2 inhibitory ligand cimetidine(+). HEK-hOCT2-C exhibited different functional properties when they were confluent or had been dissociated by removal of Ca(2+) and Mg(2+). Only confluent HEK-hOCT2-C transported Cd(2+), and confluent and dissociated cells exhibited different potencies for inhibition of uptake of 1-methyl-4-phenylpyridinium(+) (MPP(+)) by Cd(2+), MPP(+), tetraethylammonium(+), cimetidine(+), and corticosterone. In confluent HEK-hOCT2-C, largely different inhibitor potencies were obtained upon comparison of inhibition of Cd(2+) uptake, 4-[4-(dimethylamino)styryl]-N-methylpyridinium(+) (ASP(+)) uptake, and MPP(+) uptake using substrate concentrations far below the respective Km values. Employing a point mutation in the previously identified substrate binding site of rat Oct1 produced evidence that short distance allosteric effects between binding sites for substrates and inhibitors are involved in substrate-dependent inhibitor potency. Substrate-dependent inhibitor affinity is probably a common property of OCTs. To predict interactions between drugs that are transported by OCTs and inhibitory drugs, it is necessary to employ the specific transported drug rather than a model substrate for in vitro measurements.