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Abstract Background The impact of chronic obstructive pulmonary disease (COPD) on outcome in perioperative organ injury (POI) has not yet been investigated sufficiently. Methods This retrospective cohort study analysed data of surgical patients with POI, namely delirium, stroke, acute myocardial infarction, acute respiratory distress syndrome, acute liver injury (ALI), or acute kidney injury (AKI), in Germany between 2015 and 2019. We compared in-hospital mortality, hospital length of stay (HLOS) and perioperative ventilation time (VT) in patients with and without COPD. Results We analysed the data of 1,642,377 surgical cases with POI of which 10.8% suffered from COPD. In-hospital mortality was higher (20.6% vs. 15.8%, p

Abstract To elucidate the adaptation of the right ventricle to acute and intermittently sustained afterload elevation, targeted preload reductions and afterload increases were implemented in a porcine model involving 12 pigs. Preload reduction was achieved via balloon occlusion of the inferior vena cava before, immediately and 5 min after acute afterload elevation induced by pulmonary artery occlusion or thromboxane A2 analog (U46619) infusion. Ventricular response was monitored by registration of pressure–volume (PV) loops using a conductance catheter. The end-systolic pressure–volume relationship (ESPVR) during pure preload reduction was adequately described by linear regression (mean and SEM slope of ESPVR (Ees) 0.414 ± 0.064 mmHg/ml), reflecting the classical Frank-Starling mechanism (FSM). The ESPVR during acute afterload elevation exhibited a biphasic trajectory with significantly distinct slopes (mean and SEM Ees bilin1: 1.256 ± 0.066 mmHg ml; Ees bilin2: 0.733 ± 0.063 mmHg ml, p

Abstract Chronic obstructive pulmonary disease (COPD) is one of the leading chronic diseases worldwide. However, the impact of COPD on outcome after percutaneous coronary intervention (PCI) remains unclear. In this retrospective cohort study, we analyzed the data of hospitalized patients undergoing PCI in Germany between 2015 and 2019. We compared in-hospital mortality, hospital length of stay and peri-interventional ventilation time (VT) in patients with and without COPD, including different COPD severity grades, COPD with exacerbation (COPDe) and infection (COPDi). We analyzed the data of 3,464,369 cases undergoing PCI. A total of 291,707 patients (8.4%) suffered from COPD. Patients suffering from COPD died more often (2.4% vs. 2.0%; p

Background: Previous studies have shown cardiac abnormalities in acute liver injury, suggesting a potential role in the associated high mortality. Methods: We designed an experimental study exploring the short-term effects of acute cholestasis-induced liver injury on cardiac function and structure in a rodent bile duct ligation (BDL) model to elucidate the potential interplay. Thirty-seven male Sprague-Dawley rats were subjected to BDL surgery (n = 28) or served as sham-operated (n = 9) controls. Transthoracic echocardiography, Doppler evaluation of the left anterior descending coronary artery, and myocardial contrast echocardiography were performed at rest and during adenosine and dobutamine stress 5 days after BDL. Immunohistochemical staining of myocardial tissue samples for hypoxia and inflammation as well as serum analysis were performed. Results: BDL animals exhibited acute liver injury with elevated transaminases, bilirubin, and total circulating bile acids (TBA) 5 days after BDL (TBA control: 0.81 ± 2.54 µmol/L vs. BDL: 127.52 ± 57.03 µmol/L; p < 0.001). Concurrently, cardiac function was significantly impaired, characterized by reduced cardiac output (CO) and global longitudinal strain (GLS) in the echocardiography at rest and under pharmacological stress (CO rest control: 120.6 ± 24.3 mL/min vs. BDL 102.5 ± 16.6 mL/min, p = 0.041; GLS rest control: −24.05 ± 3.8% vs. BDL: −18.5 ± 5.1%, p = 0.01). Myocardial perfusion analysis revealed a reduced myocardial blood flow at rest and a decreased coronary flow velocity reserve (CFVR) under dobutamine stress in the BDL animals (CFVR control: 2.1 ± 0.6 vs. BDL: 1.7 ± 0.5 p = 0.047). Immunofluorescence staining indicated myocardial hypoxia and increased neutrophil infiltration. Conclusions: In summary, acute cholestasis-induced liver injury can lead to impaired cardiac function mediated by coronary microvascular dysfunction, suggesting that major adverse cardiac events may contribute to the mortality of acute liver failure. This may be due to endothelial dysfunction and direct bile acid signaling.

Abstract Background Coronary physiology assessment in rodents by ultrasound is an excellent noninvasive and easy to perform technique, including pulsed-wave Doppler (PWD) and myocardial contrast echocardiography (MCE). Both techniques and the corresponding calculated parameters were investigated in this study at rest as well as their response to pharmacologically induced stress. Methods Left ventricular myocardial function was assessed in eight anaesthetised rats using transthoracic echocardiography. Coronary physiology was assessed by both PWD of the left coronary artery and MCE using a bolus method. Measurements were performed at rest and under stimulation with adenosine and dobutamine. Effects of stimulation on the calculated parameters were evaluated and rated by effect size (η 2). Results Changes could be demonstrated by selected parameters of PWD and MCE. The clearest effect in PWD was found for diastolic peak velocity (η 2 = 0.58). It increased from 528 ± 110 mm/s (mean ± standard deviation) at rest to 839 ± 342 mm/s (p = 0.001) with adenosine and 1093 ± 302 mm/s with dobutamine (p = 0.001). The most distinct effect from MCE was found for the normalised wash-in rate (η 2 = 0.58). It increased from 1.95 ± 0.35% at rest to 3.87 ± 0.85% with adenosine (p = 0.001) and 3.72 ± 1.03% with dobutamine (p = 0.001). Conclusion Induced changes in coronary physiology by adenosine and dobutamine could successfully be monitored using MCE and PWD in anaesthetised rats. Due to the low invasiveness of the measurements, this protocol could be used for longitudinal animal studies.

Severity assessment in animals is an ongoing field of research. In particular, the question of objectifiable and meaningful parameters of score-sheets, as well as their best combination, arise. This retrospective analysis investigates the suitability of a score-sheet for assessing severity and seeks to optimise it for predicting survival in 89 male Sprague Dawley rats (Rattus norvegicus), during an experiment evaluating the influence of liver cirrhosis by bile duct ligation (BDL) on vascular healing. The following five parameters were compared for their predictive power: (i) overall score; (ii) relative weight loss; (iii) general condition score; (iv) spontaneous behaviour score; and (v) the observer’s assessment whether pain might be present. Suitable cut-off values of these individual parameters and the combination of multiple parameters were investigated. A total of ten rats (11.2%; 10/89) died or had to be sacrificed at an early stage due to pre-defined humane endpoints. Neither the overall score nor any individual parameter yielded satisfactory results for predicting survival. Using retrospectively calculated cut-off values and combining the overall score with the observer’s assessment of whether the animal required analgesia (dipyrone) for pain relief resulted in an improved prediction of survival on the second post-operative day. This study demonstrates that combining score parameters was more suitable than using single ones and that experienced human judgement of animals can be useful in addition to objective parameters in the assessment of severity. By optimising the score-sheet and better understanding the burden of the model on rats, this study contributes to animal welfare.

Abstract The linearity and load insensitivity of the end-systolic pressure–volume-relationship (ESPVR), a parameter that describes the ventricular contractile state, are controversial. We hypothesize that linearity is influenced by a variable overlay of the intrinsic mechanism of autoregulation to afterload (shortening deactivation) and preload (Frank-Starling mechanism). To study the effect of different short-term loading alterations on the shape of the ESPVR, experiments on twenty-four healthy pigs were executed. Preload reductions, afterload increases and preload reductions while the afterload level was increased were performed. The ESPVR was described either by a linear or a bilinear regression through the end-systolic pressure volume (ES-PV) points. Increases in afterload caused a biphasic course of the ES-PV points, which led to a better fit of the bilinear ESPVRs (r2 0.929 linear ESPVR vs. r2 0.96 and 0.943 bilinear ESPVR). ES-PV points of a preload reduction on a normal and augmented afterload level could be well described by a linear regression (r2 0.974 linear ESPVR vs. r2 0.976 and 0.975 bilinear ESPVR). The intercept of the second ESPVR (V0) but not the slope demonstrated a significant linear correlation with the reached afterload level (effective arterial elastance Ea). Thus, the early response to load could be described by the fixed slope of the ESPVR and variable V0, which was determined by the actual afterload. The ESPVR is only apparently nonlinear, as its course over several heartbeats was affected by an overlay of SDA and FSM. These findings could be easily transferred to cardiovascular simulation models to improve their accuracy.

To investigate whether acute liver failure (ALF) leads to secondary acute myocardial injury, 100 ALF patients that were retrospectively identified in a single center based on ICD 10 codes and 8 rats from an experimental study that died early after bile duct ligation (BDL) were examined. Creatine kinase (CK), creatine kinase-MB isoenzyme (CKMB) and cardiac troponin-I (cTnI) were analyzed as markers of myocardial injury. For histological analysis, hematoxylin-eosin (HE), elastic Van Gieson (EVG), CD41 and myeloperoxidase were used to stain rat hearts. Major adverse cardiac events (MACEs) were a critical factor for mortality (p = 0.037) in human ALF. Deceased patients exhibited higher levels of CKMB than survivors (p = 0.023). CKMB was a predictor of mortality in ALF (p = 0.013). Animals that died early after BDL exhibited increased cTnI, CKMB, tumor necrosis factor α (TNFα) and interleukin-6 (IL-6) levels compared to controls (cTnI: p = 0.011, CKMB: p = 0.008, TNFα: p = 0.003, IL-6: p = 0.006). These animals showed perivascular lesions and wavy fibers, microthrombi and neutrophilic infiltration in the heart. MACEs are decisive for mortality in human ALF, and elevated CKMB values indicate that this might be due to structural myocardial damage. Accordingly, CKMB was found to have predictive value for mortality in ALF. The results are substantiated by data from a rat BDL model demonstrating diffuse myocardial injury.

(1) Introduction: The intraperitoneal onlay mesh technique (IPOM) is widely used to repair incisional hernias. This method has advantages but suffers from complications due to intraperitoneal adhesion formation between the mesh and intestine. An ideal mesh minimizes adhesions and shows good biocompatibility. To address this, newly developed multifilamentous polyethylene (PET) meshes were constructed from sub-macrophage-sized monofilaments and studied regarding biocompatibility and adhesion formation. (2) Methods: We investigated fine (FPET, 72 filaments, 11 µm diameter each) and ultra-fine multifilament (UFPET, 700 filaments, 3 µm diameter each) polyethylene meshes for biocompatibility in subcutaneous implantation in rats. Adhesion formation was analyzed in the IPOM position in rabbits. Geometrically identical mono-filamentous polypropylene (PP) Bard Soft® PP meshes were used for comparison. Histologic and immune-histologic foreign body reactions were assessed in 48 rats after 7 or 21 days (four mesh types, with two different mesh types per rat; n = 6 per mesh type). Additionally, two different mesh types each were placed in the IPOM position in 24 rabbits to compile the Diamond peritoneal adhesion score after the same timeframes. The biocompatibility and adhesion score differences were analyzed with the Kruskal–Wallis nonparametric statistical test. (3) Results: Overall, FPET and, especially, UFPET showed significantly smaller foreign body granulomas compared to PP meshes. Longer observation periods enhanced the differences. Immunohistology showed no significant differences in the cellular immune response and proliferation. UFPET demonstrated significantly reduced peritoneal adhesion formation compared to all other tested meshes after 21 days. (4) Conclusions: Overall, FPET and, especially, UFPET demonstrated their suitability for IPOM hernia meshes in animal models by improving major aspects of the foreign body reaction and reducing adhesion formation.

Many computer simulation models of the cardiovascular system, of varying complexity and objectives, have been proposed in physiological science. Every model needs to be parameterized and evaluated individually. We conducted a porcine animal model to parameterize and evaluate a computer simulation model, recently proposed by our group. The results of an animal model, on thirteen healthy pigs, were used to generate consistent parameterization data for the full heart computer simulation model. To evaluate the simulation model, differences between the resulting simulation output and original animal data were analysed. The input parameters of the animal model, used to individualize the computer simulation, showed high interindividual variability (range of coefficient of variation: 10.1–84.5%), which was well-reflected by the resulting haemodynamic output parameters of the simulation (range of coefficient of variation: 12.6–45.7%). The overall bias between the animal and simulation model was low (mean: −3.24%, range: from −26.5 to 20.1%). The simulation model used in this study was able to adapt to the high physiological variability in the animal model. Possible reasons for the remaining differences between the animal and simulation model might be a static measurement error, unconsidered inaccuracies within the model, or unconsidered physiological interactions.

OBJECTIVE:A simple but reliable and safe anaesthetic procedure is required for surgical interventions in small rodents. Combined ketamine and xylazine injections are often used in rats for less invasive surgery, possibly with spontaneous breathing and without airway management. However, there are important pitfalls to be avoided by special precautions and monitoring, as shown subsequently. STUDY DESIGN:Observational study. ANIMALS:Twenty-four anaesthetic procedures for bile duct ligation, sham operation or carotid artery dilatation in 20 male Sprague-Dawley rats, preoperatively weighing between 440 and 550 g. METHODS:Intolerable high mortality rates occurred in the first 7 postoperative days while establishing a new experimental model in rats using ketamine-xylazine anaesthesia. Rats were spontaneously breathing ambient air during the first 12 surgeries without airway management. An observed high mortality rate in these animals led to a change in the trial protocol: the insufflation of 2 litres of oxygen per minute via nose cone during the following 12 rat surgeries. Retrospective comparison of the outcome (without oxygen vs. with oxygen insufflation) was conducted. RESULTS:The perioperative mortality rate could be significantly reduced from 58% (7/12) to 17% (2/12) (p = 0.036) by oxygen insufflation via nose cone. Significantly different levels of intraoperative oxygen saturation (SpO2; 89 ± 4% [without oxygen] vs. 97 ± 0.5% [with oxygen], p < 0.0001), but no significant differences in heart rate (HR; 267 ± 7 beats minute-1 [bpm] [without oxygen] vs. 266 ± 6 bpm [with oxygen], p = 0.955) were observed. CONCLUSIONS AND CLINICAL RELEVANCE:In summary, rats under ketamine-xylazine anaesthesia are susceptible to hypoxia. This may lead to increased delayed mortality related to hypoxia induced lung failure. Apparently, this is an underestimated problem. We highly recommend using additional oxygen insufflation in spontaneously breathing rats under ketamine-xylazine anaesthesia with basic monitoring such as measurement of oxygen saturation.

The aim of the study is to clear the significance of craft skills for the pupils in age nine and twelve years. More than 200 pupils were asked to define, what are the most important skills for the pupils of their age. The results bring out that category of the skills related to craft subject is of the most presented categories in pupils' self description. Thus the primary school pupils essentially defined themselves by the activities they could do practically (building, cooking, repairing of things). The most undefined relation to craft activities is reflected in the answer of smaller boys in our study. A suspicion arisen from the analysis of pupils' sayings, that the craft lessons in the 1st school stage tend to be organized kind of poorly was asserted by the teachers who pointed out the need for special rooms and materials to implement different techniques.

The aim of the study is to clear the significance of craft skills for the pupils in age nine and twelve years. More than 200 pupils were asked to define, what are the most important skills for the pupils of their age. The results bring out that category of the skills related to craft subject is of the most presented categories in pupils' self description. Thus the primary school pupils essentially defined themselves by the activities they could do practically (building, cooking, repairing of things). The most undefined relation to craft activities is reflected in the answer of smaller boys in our study. A suspicion arisen from the analysis of pupils' sayings, that the craft lessons in the 1st school stage tend to be organized kind of poorly was asserted by the teachers who pointed out the need for special rooms and materials to implement different techniques.