Impact of late gadolinium enhancement image acquisition resolution on neural network based automatic scar segmentation.

BACKGROUND: Automatic myocardial scar segmentation from late gadolinium enhancement (LGE) images using neural networks promises an alternative to time-consuming and observer-dependent semi-automatic approaches. However, alterations in data acquisition, reconstruction as well as post-processing may compromise network performance. The objective of the present work was to systematically assess network performance degradation due to a mismatch of point-spread function between training and testing data. METHODS: Thirty-six high-resolution (0.7×0.7×2.0 mm3) LGE k-space datasets were acquired post-mortem in porcine models of myocardial infarction. The in-plane point-spread function and hence in-plane resolution Δx was retrospectively degraded using k-space lowpass filtering, while field-of-view and matrix size were kept constant. Manual segmentation of the left ventricle (LV) and healthy remote myocardium was performed to quantify location and area (% of myocardium) of scar by thresholding (≥ SD5 above remote). Three standard U-Nets were trained on training resolutions Δxtrain = 0.7, 1.2 and 1.7 mm to predict endo- and epicardial borders of LV myocardium and scar. The scar prediction of the three networks for varying test resolutions (Δxtest = 0.7 to 1.7 mm) was compared against the reference SD5 thresholding at 0.7 mm. Finally, a fourth network trained on a combination of resolutions (Δxtrain = 0.7 to 1.7 mm) was tested. RESULTS: The prediction of relative scar areas showed the highest precision when the resolution of the test data was identical to or close to the resolution used during training. The median fractional scar errors and precisions (IQR) from networks trained and tested on the same resolution were 0.0 percentage points (p.p.) (1.24 - 1.45), and - 0.5 - 0.0 p.p. (2.00 - 3.25) for networks trained and tested on the most differing resolutions, respectively. Deploying the network trained on multiple resolutions resulted in reduced resolution dependency with median scar errors and IQRs of 0.0 p.p. (1.24 - 1.69) for all investigated test resolutions. CONCLUSION: A mismatch of the imaging point-spread function between training and test data can lead to degradation of scar segmentation when using current U-Net architectures as demonstrated on LGE porcine myocardial infarction data. Training networks on multi-resolution data can alleviate the resolution dependency.

Toward the "Perfect" Shunt: Historical Vignette, Current Efforts, and Future Directions.

As a concept, drainage of excess fluid volume in the cranium has been around for more than 1000 years. Starting with the original decompression-trepanation of Abulcasis to modern programmable shunt systems, to other nonshunt-based treatments such as endoscopic third ventriculostomy and choroid plexus cauterization, we have come far as a field. However, there are still fundamental limitations that shunts have yet to overcome: namely posture-induced over- and underdrainage, the continual need for valve opening pressure especially in pediatric cases, and the failure to reinstall physiologic intracranial pressure dynamics. However, there are groups worldwide, in the clinic, in industry, and in academia, that are trying to ameliorate the current state of the technology within hydrocephalus treatment. This chapter aims to provide a historical overview of hydrocephalus, current challenges in shunt design, what members of the community have done and continue to do to address these challenges, and finally, a definition of the "perfect" shunt is provided and how the authors are working toward it.

Observations and findings during the development of a subnormothermic/normothermic long-term ex vivo liver perfusion machine.

BACKGROUND: Ex situliver machine perfusion at subnormothermic/normothermic temperature isincreasingly applied in the field of transplantation to store and evaluateorgans on the machine prior transplantation. Currently, various perfusionconcepts are in clinical and preclinical applications. Over the last 6 years ina multidisciplinary team, a novel blood based perfusion technology wasdeveloped to keep a liver alive and metabolically active outside of the bodyfor at least one week. METHODS: Within thismanuscript, we present and compare three scenarios (Group 1, 2 and 3) we werefacing during our research and development (R&D) process, mainly linked tothe measurement of free hemoglobin and lactate in the blood based perfusate. Apartfrom their proven value in liver viability assessment (ex situ), these twoparameters are also helpful in R&D of a long-term liver perfusion machine and moreover supportive in the biomedical engineering process. RESULTS: Group 1 ("good" liver on the perfusion machine) represents the best liver clearance capacity for lactate and free hemoglobin wehave observed. In contrast to Group 2 ("poor" liver on the perfusion machine), that has shown the worst clearance capacity for free hemoglobin. Astonishingly,also for Group 2, lactate is cleared till the first day of perfusion andafterwards, rising lactate values are detected due to the poor quality of theliver. These two perfusate parametersclearly highlight the impact of the organ quality/viability on the perfusion process. Whereas Group 3 is a perfusion utilizing a blood loop only (without a liver). CONCLUSION: Knowing the feasible ranges (upper- and lower bound) and the courseover time of free hemoglobin and lactate is helpful to evaluate the quality ofthe organ perfusion itself and the maturity of the developed perfusion device. Freehemoglobin in the perfusate is linked to the rate of hemolysis that indicates how optimizing (gentle blood handling, minimizing hemolysis) the perfusion machine actually is. Generally, a reduced lactate clearancecapacity can be an indication for technical problems linked to the blood supplyof the liver and therefore helps to monitor the perfusion experiments.Moreover, the possibility is given to compare, evaluate and optimize developed liverperfusion systems based on the given ranges for these two parameters. Otherresearch groups can compare/quantify their perfusate (blood) parameters withthe ones in this manuscript. The presented data, findings and recommendations willfinally support other researchers in developing their own perfusion machine ormodifying commercially availableperfusion devices according to their needs.

Tissue Glue-Based Sealing Patch for the in vivo Prevention of Iatrogenic Prelabor Preterm Rupture of Fetal Membranes.

INTRODUCTION: One of the main concerns for all fetal surgeries is the risk of preterm delivery due to the preterm prelabor rupture of the fetal membranes (iPPROM). Clinical approaches to seal fetal membrane (FM) defects are missing due to the lack of appropriate strategies to apply sealing biomaterials at the defect site. METHODS: Here, we test the performance of a previously developed strategy to seal FM defects with cyanoacrylate-based sealing patches in an ovine model up to 24 days after application. RESULTS: Patches sealed tightly the fetoscopy-induced FM defects and remained firmly attached to the defect over 10 days. At 10 days after treatment, 100% (13/13) of the patches were attached to the FMs, and 24 days after treatment 25% (1/4) of the patches placed in CO2 insufflation, and 33% (1/3) in NaCl infusion remained. However, all successfully applied patches (20/24) led to a watertight sealing at 10 or 24 days after treatment. Histological analysis indicated that cyanoacrylates induced a moderate immune response and disrupted the FM epithelium. CONCLUSION: Together, these data show the feasibility of minimally invasive sealing of FM defects by locally gathering tissue adhesive. Further development to combine this technology with refined tissue glues or healing-inducing materials holds great promise for future clinical translation.

Synthesis of coagulation factors during long-term ex situ liver perfusion.

Robust viability assessment of grafts during normothermic liver perfusion is a prerequisite for organ use. Coagulation parameters are used commonly for liver assessment in patients. However, they are not yet included in viability assessment during ex situ perfusion. In this study, we analysed coagulation parameters during one week ex situ perfusion at 34℃. Eight discarded human livers were perfused with blood-based, heparinised perfusate for one week; perfusions in a further four livers were terminated on day 4 due to massive ongoing cell death. Coagulation parameters were well below the physiologic range at perfusion start. Physiologic levels were achieved within the first two perfusion days for factor V (68.5 ± 35.5%), factor VII (83.5 ± 26.2%), fibrinogen (2.1 ± 0.4 g/L) and antithrombin (107 ± 26.5%) in the livers perfused for one week. Despite the increased production of coagulation factors, INR was detectable only at 24h of perfusion (2.1 ± 0.3) and prolonged thereafter (INR > 9). The prolongation of INR was related to the high heparin level in the perfusate (anti-FXa > 3 U/mL). Intriguingly, livers with ongoing massive cell death also disclosed synthesis of factor V and improved INR. In summary, perfused livers were able to produce coagulation factors at a physiological level ex situ. We propose that single coagulation factor analysis is more reliable for assessing the synthetic function of perfused livers as compared to INR when using a heparinised perfusate.

In vivo Sealing of Fetoscopy-Induced Fetal Membrane Defects by Mussel Glue.

INTRODUCTION: The benefits of fetal surgery are impaired by the high incidence of iatrogenic preterm prelabor rupture of the fetal membranes (iPPROM), for which chorioamniotic separation has been suggested as a potential initiator. Despite the urgent need to prevent iPPROM by sealing the fetoscopic puncture site after intervention, no approach has been clinically translated. METHODS: A mussel-inspired biomimetic glue was tested in an ovine fetal membrane (FM) defect model. The gelation time of mussel glue (MG) was first optimized to make it technically compatible with fetal surgery. Then, the biomaterial was loaded in polytetrafluoroethylene-coated nitinol umbrella-shaped receptors and applied on ovine FM defects (N = 10) created with a 10 French trocar. Its sealing performance and tissue response were analyzed 10 days after implantation by amniotic fluid (AF) leakage and histological methods. RESULTS: All ewes and fetuses recovered well after the surgery, and 100% ewe survival and 91% fetal survival were observed at explantation. All implants were tight at explantation, and no AF leakage was observed in any of them. Histological analysis revealed a mild tissue response to the implanted glue. CONCLUSION: MG showed promising properties for the sealing of FM defects and thereby the prevention of preterm birth. Studies to analyze the long-term tissue response to the sealant should be performed.

Cardiovascular magnetic resonance imaging of functional and microstructural changes of the heart in a longitudinal pig model of acute to chronic myocardial infarction.

BACKGROUND: We examined the dynamic response of the myocardium to infarction in a longitudinal porcine study using relaxometry, functional as well as diffusion cardiovascular magnetic resonance (CMR). We sought to compare non contrast CMR methods like relaxometry and in-vivo diffusion to contrast enhanced imaging and investigate the link of microstructural and functional changes in the acute and chronically infarcted heart. METHODS: CMR was performed on five myocardial infarction pigs and four healthy controls. In the infarction group, measurements were obtained 2 weeks before 90 min occlusion of the left circumflex artery, 6 days after ischemia and at 5 as well as 9 weeks as chronic follow-up. The timing of measurements was replicated in the control cohort. Imaging consisted of functional cine imaging, 3D tagging, T2 mapping, native as well as gadolinium enhanced T1 mapping, cardiac diffusion tensor imaging, and late gadolinium enhancement imaging. RESULTS: Native T1, extracellular volume (ECV) and mean diffusivity (MD) were significantly elevated in the infarcted region while fractional anisotropy (FA) was significantly reduced. During the transition from acute to chronic stages, native T1 presented minor changes (< 3%). ECV as well as MD increased from acute to the chronic stages compared to baseline: ECV: 125 ± 24% (day 6) 157 ± 24% (week 5) 146 ± 60% (week 9), MD: 17 ± 7% (day 6) 33 ± 14% (week 5) 29 ± 15% (week 9) and FA was further reduced: - 31 ± 10% (day 6) - 38 ± 8% (week 5) - 36 ± 14% (week 9). T2 as marker for myocardial edema was significantly increased in the ischemic area only during the acute stage (83 ± 3 ms infarction vs. 58 ± 2 ms control p < 0.001 and 61 ± 2 ms in the remote area p < 0.001). The analysis of functional imaging revealed reduced left ventricular ejection fraction, global longitudinal strain and torsion in the infarct group. At the same time the transmural helix angle (HA) gradient was steeper in the chronic follow-up and a correlation between longitudinal strain and transmural HA gradient was detected (r = 0.59 with p < 0.05). Comparing non-gadolinium enhanced data T2 mapping showed the largest relative change between infarct and remote during the acute stage (+ 33 ± 4% day 6, with p = 0.013 T2 vs. MD, p = 0.009 T2 vs. FA and p = 0.01 T2 vs. T1) while FA exhibited the largest relative change between infarct and remote during the chronic follow-up (+ 31 ± 2% week 5, with p = N.S. FA vs. MD, p = 0.03 FA vs. T2 and p = 0.003 FA vs. T1). Overall, diffusion parameters provided a higher contrast (> 23% for MD and > 27% for FA) during follow-up compared to relaxometry (T1 17-18%/T2 10-20%). CONCLUSION: During chronic follow-up after myocardial infarction, cardiac diffusion tensor imaging provides a higher sensitivity for mapping microstructural alterations when compared to non-contrast enhanced relaxometry with the added benefit of providing directional tensor information to assess remodelling of myocyte aggregate orientations, which cannot be otherwise assessed.

Minimally Invasive Precise Application of Bioadhesives to Prevent IPPROM on a Pregnant Sheep Model.

INTRODUCTION: Iatrogenic preterm premature rupture of the membrane remains the Achille's heel of fetoscopy. The aim of this study was to show in vivo feasibility of fetal membrane (FM) defect sealing by the application of tissue glues with umbrella-shaped receptors. METHODS: First, we adapted our previously described ex vivo strategy and evaluated the adhesion strength of different tissue glues, Histoacryl® and Glubran2®, by bonding polytetrafluoroethylene or silicone encapsulated nitinol glue receptor to human FM. Then, we exposed pregnant sheep uterus through a laparotomy and placed a 10-French trocar into the amniotic cavity through which the umbrella-shaped glue receptor (n = 9) was inserted and fixated onto the FM with the tissue glues (n = 8). The tightness of the sealed defects was assessed 4 h post-surgery. RESULTS: Both tissue glues tested resulted in adhesion of the glue receptors to the FM ex vivo. In vivo, all glue receptors opened in the amniotic cavity (n = 9) and all successfully placed glue receptors sealed the FM defect (n = 8). Four hours post-surgery, 2 treatment sites showed minimal leakage whereas the negative control without glue (n = 1) showed substantial leakage. DISCUSSION: This in vivo study confirms that fetoscopically induced FM defects can be sealed by the application of tissue adhesives.

Efficacy of catheter-based drug delivery in a hybrid in vitro model of cardiac microvascular obstruction with porcine microthrombi.

Microvascular obstruction (MVO) often occurs in ST-elevation myocardial infarction (STEMI) patients after percutaneous coronary intervention (PCI). Diagnosis and treatment of MVO lack appropriate and established procedures. This study focused on two major points by using an in vitro multiscale flow model, which comprised an aortic root model with physiological blood flow and a microfluidic model of the microcirculation with vessel diameters down to 50 µm. First, the influence of porcine microthrombi (MT), injected into the fluidic microchip, on perfusion was investigated. We found that only 43% of all injected MT were fully occlusive. Second, it could also be shown that the maximal concentration of a dye (representing therapeutic agent) during intracoronary infusion could be increased on average by 58%, when proximally occluding the coronary artery by a balloon during drug infusion. The obtained results and insights enhance the understanding of perfusion in MVO-affected microcirculation and could lead to improved treatment methods for MVO patients.

One-Year Outcome of an Ongoing Pre-Clinical Growing Animal Model for a Tissue-Engineered Valved Pulmonary Conduit.

Objectives: A self-constructed valved pulmonary conduit made out of a de-cellularized porcine small intestinal submucosal extracellular matrix biological scaffold was tested in a chronic growing lamb model. Methods: The conduit was implanted in pulmonary valve position in 19 lambs. We monitored clinical, laboratory, and echocardiographic findings until 12 months after surgery. In two animals, euthanasia was planned at nine and twelve months. Pre-mortem chest computed tomography and post-mortem pathologic work up were performed. Data are presented as frequency and percentage, median and range, or mean and standard deviation. Results: Twelve (63.2%) animals survived the perioperative period. Three unexpected deaths occurred during the follow-up period: one due to aspiration pneumonia at 23 days after surgery, and two due to early and late infective endocarditis of the conduit at 18 and 256 days. In the two animals with planned scarification, the pre-mortem CT scan revealed mild or no calcification within the conduit or valve leaflets. In the echocardiographic examination at 12 months, peak and mean systolic pressure gradients across the conduit valve were 6.5 (3-21) mmHg and 3 (2-12) mmHg, while valve regurgitation was none (n = 2), trivial (n = 5), moderate (n = 1), or severe (n = 1). No clinical or laboratory signs of hemolysis were seen. After 12 months of follow-up, the animals' body weights had increased from 33 (27-38) kg to 53 (38-66) kg (p = 0.010). Conclusions: Implantation of a valved pulmonary conduit in our growing lamb model was feasible. Infective endocarditis of the implanted valved conduit remained a significant complication.

A Soft Robotic Actuator System for In Vivo Modeling of Normal Pressure Hydrocephalus.

OBJECTIVE: The intracranial pressure (ICP) affects the dynamics of cerebrospinal fluid (CSF) and its waveform contains information that is of clinical importance in medical conditions such as hydrocephalus. Active manipulation of the ICP waveform could enable the investigation of pathophysiological processes altering CSF dynamics and driving hydrocephalus. METHODS: A soft robotic actuator system for intracranial pulse pressure amplification was developed to model normal pressure hydrocephalus in vivo. Different end actuators were designed for intraventricular implantation and manufactured by applying cyclic tensile loading on soft rubber tubing. Their mechanical properties were investigated, and the type that achieved the greatest pulse pressure amplification in an in vitro simulator of CSF dynamics was selected for application in vivo. A hydraulic actuation device based on a linear voice coil motor was developed to enable automated and fast operation of the end actuators. The combined system was validated in an acute ovine pilot in vivo study. RESULTS: in vitro results show that variations in the used materials and manufacturing settings altered the end actuator's dynamic properties, such as the pressure-volume characteristics. In the in vivo model, a cardiac-gated actuation volume of 0.125 mL at a heart rate of 62 bpm caused an increase of 205% in mean peak-to-peak amplitude but only an increase of 1.3% in mean ICP. CONCLUSION: The introduced soft robotic actuator system is capable of ICP waveform manipulation. SIGNIFICANCE: Continuous amplification of the intracranial pulse pressure could enable in vivo modeling of normal pressure hydrocephalus and shunt system testing under pathophysiological conditions to improve therapy for hydrocephalus.

Systemic acylcarnitine levels are affected in response to multiple injuries and hemorrhagic shock: An analysis of lipidomic changes in a standardized porcine model.

INTRODUCTION: Along with recent advances in analytical technologies, tricarboxylic acid-cycle intermediates are increasingly identified as promising makers for cellular ischemia and mitochondrial dysfunction during hemorrhagic shock. For traumatized patients, the knowledge of the role of lipid oxidation substrates is sparse. In this study, we aimed to analyze the dynamics of systemic acylcarnitine (AcCa) release in a standardized polytrauma model with hemorrhagic shock. METHODS: Fifty-two male pigs (50 ± 5 kg) were randomized into two groups: group isolated fracture was subject to a standardized femur shaft fracture, and group polytrauma was subject to a femur fracture, followed by blunt chest trauma, liver laceration, and a pressure-controlled hemorrhagic shock for 60 minutes. Resuscitation was performed with crystalloids. Fractures were stabilized by intramedullary nailing. Venous samples were collected at six time points (baseline, trauma, resuscitation, 2 hours, 4 hours, and 6 hours). Lipidomic analysis was performed via liquid chromatography coupled mass spectrometry. Measurements were collated with clinical markers and near-infrared spectrometry measurements of tissue perfusion. Longitudinal analyses were performed with linear mixed models, and Spearman's correlations were calculated. A p value of 0.05 was defined as threshold for statistical significance. RESULTS: From a total of 303 distinct lipids, we identified two species of long-chain AcCas. Both showed a highly significant ( p < 0.001) twofold increase after hemorrhagic shock in group polytrauma that promptly normalized after resuscitation. This increase was associated with a significant decrease of the base excess ( p = 0.005), but recovery after resuscitation was faster. For both AcCas, there were significant correlations with decreased muscle tissue oxygen delivery ( p = 0.008, p = 0.003) and significant time-lagged correlations with the increase of creatine kinase ( p < 0.001, p < 0.001). CONCLUSION: Our results point to plasma AcCas as a possible indicator for mitochondrial dysfunction and cellular ischemia in hemorrhagic shock. The more rapid normalization after resuscitation in comparison with acid base changes may warrant further investigation.

Extracorporeal cytokine adsorption reduces systemic cytokine storm and improves graft function in lung transplantation.

Objectives: Ischemia-reperfusion injury often coincides with a cytokine storm, which can result in primary graft dysfunction following lung transplantation. Our previous research has demonstrated allograft improvement by cytokine adsorption during ex vivo lung perfusion. The aim of this study was to investigate the effect of in vivo extracorporeal cytokine adsorption in a large animal model. Materials and Methods: Pig left lung transplantation was performed following 24 hours of cold ischemic storage. Observation period after transplantation was 24 hours. In the treatment group (n = 6), extracorporeal CytoSorb adsorption was started 30 minutes before reperfusion and continued for 6 hours. A control group (n = 3) did not receive adsorber treatment. Results: During adsorption, we consistently noticed a significant decrease in plasma proinflammatory interleukin (IL)-2, trends of less proinflammatory, tumor necrosis factor- α, IL-1α, and granulocyte-macrophage colony-stimulating factor as well as significantly reduced systemic neutrophils. In addition, a significantly lower peak airway pressure was detected during the 6 hours of adsorption. After 24 hours of observation, when evaluating the left lung allograft independently, we observed significantly improved CO2 removal, partial pressure of oxygen/inspired oxygen fraction ratio, and less acidosis in the treatment group. At autopsy, bronchoalveolar lavage results exhibited significantly lower recruitment of cells and less pro-inflammatory IL-1α, IL-1ß, IL-6, and IL-8 in the treatment group. Histologically, the treatment group had a strong trend, indicating less neutrophil invasion into the alveolar space. Conclusions: Based on our findings, cytokine adsorption during and after reperfusion is a viable approach to reducing posttransplant inflammation following lung transplantation. CytoSorb may increase the acceptance of extended criteria donor lungs, which are more susceptible to ischemia-reperfusion injury.

Continuous Monitoring of Blood Pressure and Vascular Hemodynamic Properties With Miniature Extravascular Hall-Based Magnetic Sensor.

Continuous measurement of vascular and hemodynamic parameters could improve monitoring of disease progression and enable timely clinical decision making and therapy surveillance in patients suffering from cardiovascular diseases. However, no reliable extravascular implantable sensor technology is currently available. Here, we report the design, characterization, and validation of an extravascular, magnetic flux sensing device capable of capturing the waveforms of the arterial wall diameter, arterial circumferential strain, and arterial pressure without restricting the arterial wall. The implantable sensing device, comprising a magnet and a magnetic flux sensing assembly, both encapsulated in biocompatible structures, has shown to be robust, with temperature and cyclic-loading stability. Continuous and accurate monitoring of arterial blood pressure and vascular properties was demonstrated with the proposed sensor in vitro with a silicone artery model and validated in vivo in a porcine model mimicking physiologic and pathologic hemodynamic conditions. The captured waveforms were further used to deduce the respiration frequency, the duration of the cardiac systolic phase, and the pulse wave velocity. The findings of this study not only suggest that the proposed sensing technology is a promising platform for accurate monitoring of arterial blood pressure and vascular properties, but also highlight the necessary changes in the technology and the implantation procedure to allow the translation of the sensing device in the clinical setting.

The influence of upright posture on craniospinal, arteriovenous, and abdominal pressures in a chronic ovine in-vivo trial.

INTRODUCTION: Most investigations into postural influences on craniospinal and adjacent physiology have been performed in anesthetized animals. A comprehensive study evaluating these physiologies while awake has yet been completed. METHODS: Six awake sheep had telemetric pressure sensors (100 Hz) implanted to measure intracranial, intrathecal, arterial, central venous, cranial, caudal, dorsal, and ventral intra-abdominal pressure (ICP, ITP, ABP, CVP, IAPcr, IAPcd, IAPds, IAPve, respectively). They were maneuvered upright by placing in a chair for two minutes; repeated 25 times over one month. Changes in mean and pulse pressure were calculated by comparing pre-chair, P0, with three phases during the maneuver: P1, chair entrance; P2, chair halftime; P3, prior to chair exit. Statistical significance (p ≤ .05) was assessed using repeated measures ANOVA. RESULTS: Significant mean pressure changes of (P1 - P0) and (P3 - P0) were measured at - 12.1 ± 3.1 and - 14.2 ± 3.0(p < .001), 40.8 ± 10.5 and 37.7 ± 3.5(p = .019), 9.7 ± 8.3 and 6.2 ± 5.3(p = .012), 22.3 ± 29.8 and 12.5 ± 12.1(p = .042), and 11.7 ± 3.9 and 9.0 ± 5.2(p = .014) mmHg, for ICP, ITP, IAPds, IAPcr, IAPca, respectively. For pulse pressures, significant changes of (P1 - P0) and (P3 - P0) were measured at - 1.3 ± 0.7 and - 2.0 ± 1.1(p < .001), 4.7 ± 2.3 and 1.4 ± 1.4(p < .001), 15.0 ± 10.2 and 7.3 ± 5.5(p < .001), - 0.7 ± 1.8 and - 1.7 ± 1.7(p < .001), - 1.3 ± 4.2 and - 1.4 ± 4.7(p = .006), and 0.3 ± 3.9 and - 1.0 ± 1.3(p < .001) mmHg, for ICP, ITP, ABP, IAPds, IAPcr, IAPca, respectively. CONCLUSIONS: Pressures changed posture-dependently to differing extents. Changes were most pronounced immediately after entering upright posture (P1) and became less prominent over the chair duration (P2-to-P3), suggesting increased physiologic compensation. Dynamic changes in IAP varied across abdominal locations, motivating the abdominal cavity not to be considered as a unified entity, but sub-compartments with individual dynamics.

Influence of head-over-body and body-over-head posture on craniospinal, vascular, and abdominal pressures in an acute ovine in-vivo model.

INTRODUCTION: Optimal shunt-based hydrocephalus treatments are heavily influenced by dynamic pressure behaviors between proximal and distal ends of shunt catheters. Posture-dependent craniospinal, arterial, venous, and abdominal dynamics thereby play an essential role. METHODS: An in-vivo ovine trial (n = 6) was conducted to evaluate communication between craniospinal, arterial, venous, and abdominal dynamics. Tilt-testing was performed between -13° and + 13° at 10-min intervals starting and ending at 0° prone position. Mean pressure, pulse pressure, and Pearson correlation (r) to the respective angle were calculated. Correlations are defined as strong: |r|≥ 0.7, mild: 0.3 <|r|< 0.7, and weak: |r|≤ 0.3. Transfer functions (TFs) between the arterial and adjacent compartments were derived. RESULTS: Strong correlations were observed between posture and: mean carotid/femoral arterial (r = - 0.97, r = - 0.87), intracranial, intrathecal (r = - 0.98, r = 0.94), jugular (r = - 0.95), abdominal cranial, dorsal, caudal, and intravesical pressure (r = - 0.83, r = 0.84, r = - 0.73, r = 0.99) while mildly positive correlation exists between tilt and central venous pressure (r = 0.65). Only dorsal abdominal pulse pressure yielded a significant correlation to tilt (r = 0.21). TFs followed general lowpass behaviors with resonant peaks at 4.2 ± 0.4 and 11.5 ± 1.5 Hz followed by a mean roll-off of - 15.9 ± 6.0 dB/decade. CONCLUSIONS: Tilt-tests with multi-compartmental recordings help elucidate craniospinal, arterial, venous, and abdominal dynamics, which is essential to optimize shunt-based therapy. Results motivate hydrostatic influences on mean pressure, with all pressures correlating to posture, with little influence on pulse pressure. TF results quantify the craniospinal, arterial, venous, and abdominal compartments as compliant systems and help pave the road for better quantitative models of the interaction between the craniospinal and adjacent spaces.

Physiologic Effects of Prolonged Terminal Anesthesia in Sheep (Ovis gmelini aries).

The ruminant alimentary tract and its effects on blood homeostasis complicate prolonged terminal studies conducted under general anesthesia in sheep. We therefore studied 15 healthy female white alpine sheep that were undergoing prolonged anesthesia (> 30 h) for an unrelated terminal study. In the current study, all sheep developed a decreased hematocrit and hemoglobin concentration after induction of anesthesia, which fell further, along with a significant decrease in white blood cell count, over the course of anesthesia. Sheep also showed an initial hyponatremia, a persistent hypokalemia, hypocalcemia, and a progressive hyperchloremia. A significant drop in blood pH developed over time despite normal values of blood lactate and a marked decline in partial pressure of carbon dioxide over the course of the experiment. The latter consequently reduced the efficacy of mechanical ventilation, as reflected in a reduced oxygen partial pressure. A significant increase in lactate dehydrogenase and creatinine kinase was observed. Arterial blood pressure and heart rate significantly decreased over time, but remained within normotensive and normocardic limits. Central venous pressure rose significantly over the course of anesthesia. In conclusion, prolonged anesthesia in sheep is associated with a wide range of complex physi- ologic changes. An in-depth understanding of all metabolic compensatory mechanisms and their underlying cause during prolonged anesthesia is necessary for interpreting data from the primary study, with special considerations to account for ruminant-specific physiology.

The Sheep as a Comprehensive Animal Model to Investigate Interdependent Physiological Pressure Propagation and Multiparameter Influence on Cerebrospinal Fluid Dynamics.

The present study aims to develop a suitable animal model for evaluating the physiological interactions between cerebrospinal fluid (CSF) dynamics, hemodynamics, and abdominal compartment pressures. We seek to contribute to the enhanced recognition of the pathophysiology of CSF-dependent neurological disorders like hydrocephalus and the improvement of available treatment options. To date, no comprehensive animal model of CSF dynamics exists, and establishing an accurate model will advance our understanding of complex CSF physiology. Persisting knowledge gaps surrounding the communication and pressure propagation between the cerebrospinal space and adjacent anatomical compartments exacerbate the development of novel therapies for neurological diseases. Hence, the need for further investigation of the interactions of vascular, craniospinal, and abdominal pressures remains beyond dispute. Moreover, the results of this animal study support the optimization of in vitro test benches for medical device development, e.g., ventriculoperitoneal shunts. Six female white alpine sheep were surgically equipped with pressure sensors to investigate the physiological values of intracranial, intrathecal, arterial, central venous, jugular venous, vesical pressure, and four differently located abdominal pressures. These values were measured simultaneously during the acute animal trial with sheep under general anesthesia. Both carotid and femoral arterial blood pressure indicate a reliable and comparable representation of the systematic blood pressure. However, the jugular venous pressure and the central venous pressure in sheep in dorsal recumbency do not correlate well under general anesthesia. Furthermore, there is a trend for possible comparability of lateral intraventricular and lumbar intrathecal pressure. Nevertheless, animal body position during measurements must be considered since different body constitutions can alter the horizontal line between the cerebral ventricles and the lumbar subarachnoid space. While intra-abdominal pressure measurement in the four different abdominal quadrants yielded greater inter-individual variability, intra-vesical pressure measurements in our setting delivered comparable values for all sheep. We established a novel and comprehensive ovine animal model to investigate interdependent physiologic pressure propagation and multiparameter influences on CSF dynamics. The results of this study will contribute to further in vitro bench testing, the derivation of novel quantitative models, and the development of a pathologic ovine hydrocephalus model.

Effects of Occult Hypoperfusion on Local Circulation and Inflammation - An Analysis in a Standardized Polytrauma Model.

Introduction: Occult hypoperfusion (OH) is defined as persistent lactic acidosis despite normalization of vital parameters following trauma. The aim of this study was to analyze the association of occult hypoperfusion with local circulation and inflammation of injured soft tissue in a porcine polytrauma model. Methods: This experimental study was performed with male landrace pigs who suffered a standardized polytrauma, including a femoral fracture, blunt chest trauma, liver laceration and a mean arterial pressure (MAP) controlled hemorrhagic shock. One hour after induction of trauma, the animals were resuscitated with retrograde femoral nailing, liver packing and volume replacement. Animals were stratified into Group Norm (normalizing lactate levels after resuscitation) and Group occult hypoperfusion (OH) (persistent lactate levels above 2 mmol/l with normalizing vital parameters after resuscitation). Local circulation (oxygen saturation, hemoglobin amount, blood flow) was measured with optical sensors at the subcutaneous soft tissue at the fractured extremity as well as at the stomach and colon. Local inflammatory parameters [interleukin (IL) 6, 8, 10, and heat shock protein (HSP)] were analyzed in the subcutaneous tissue of the fractured extremity. Results: Group Norm (n = 19) and Group OH (n = 5) were comparable in baseline vital and laboratory parameters. The shock severity and total amount of blood loss were comparable among Group Norm and Group OH. Following resuscitation Group OH had significantly lower local relative hemoglobin amount at the injured soft tissue of the fractured extremity when compared with Group Norm (39.4, SD 5.3 vs. 63.9, SD 27.6 A.U., p = 0.031). The local oxygenation was significantly lower in Group OH compared to Group Norm (60.4, SD 4.6 vs. 75.8, SD 12.8, p = 0.049). Local IL-6 in the fatty tissue was significantly higher in Group OH (318.3, SD 326.6 [pg/ml]) when compared with Group Norm (73.9,SD 96.3[pg/ml], p = 0.03). The local circulation at the abdominal organs was comparable in both groups. Conclusion: OH is associated with decreased local circulation and increased local inflammation at the injured soft tissue of the extremity in polytrauma. OH might reflect the severity of local soft tissue injuries, and guide treatment strategies.