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Results for “Pathology”

Search indexed bioRxiv preprints in genomics, neuroscience, cell biology and bioinformatics. Read source abstracts and check manuscript versions; preprints are not peer reviewed.

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At least 127 records · Page 7Linked to original sources

bioRxiv2018

Urinary protein changes in the early phase of smoking-induced Chronic Obstructive Pulmonary Disease in a rat model

Chronic obstructive pulmonary disease (COPD) is a group of severe respiratory diseases. Identifying COPD through early urinary biomarkers by proteomics technology may help to reduce the mortality rate of the disease, improve the quality of life of patients and reduce the burden on society. Urine samples from a COPD rat model induced by smoking were taken at week 2, week 4 and week 8. By LC-MS/MS, 15 differential proteins with human orthologs were identified. After smoking for 2 weeks when there were no significant pathological changes, 8 differential proteins were identified: 2 proteins had been reported to be markers of COPD, while 4 proteins were associated with COPD. After smoking for 4 weeks, which is when slight pathological changes were observed, 7 differential proteins were identified: 3 of them were reported to be associated with COPD, while 1 protein had been reported to be a marker of COPD. After smoking for 8 weeks, there were significant pathological changes: 5 differential proteins were identified, 3 of which were reported to be associated with COPD. The results of this study suggest that differential urinary proteins may provide important clues for the early diagnosis of COPD.

biochemistry↗

bioRxiv2018

Cellular and Synaptic Phenotype Compensations Limit Circuit Disruption in Fmr1-KO Mouse Layer 4 Barrel Cortex but Fail to Prevent Deficits in Information Processing

Sensory hypersensitivity is a common and debilitating feature of neurodevelopmental disorders such as Fragile X Syndrome (FXS). However, how developmental changes in neuronal function ultimately culminate in the network dysfunction that underlies sensory hypersensitivities is not known. To address this, we studied the layer 4 barrel cortex circuit in Fmr1 knockout mice, a critical sensory processing circuit in this mouse model of FXS. By systematically studying cellular and synaptic properties of layer 4 neurons and combining with cellular and network simulations, we explored how the array of phenotypes in Fmr1 knockout produce circuit pathology during development that result in sensory processing dysfunction. We show that many of the cellular and synaptic pathologies in Fmr1 knockout mice are antagonistic, mitigating circuit dysfunction, and hence can be regarded as compensatory to the primary pathology. Despite this compensation, the layer 4 network in the Fmr1 knockout exhibits significant alterations in spike output in response to ascending thalamocortical input that we show results in impaired sensory encoding. We suggest that it is this developmental loss of layer 4 sensory encoding precision that drives subsequent developmental alterations in layer 4 - layer 2/3 connectivity and plasticity observed in the Fmr1 knockout, and is a critical process producing sensory hypersensitivity.

neuroscience↗

bioRxiv2018

Maternal Circulating MicroRNAs Control the Placental Response to Alcohol

Prenatal Alcohol exposure (PAE), like other pregnancy complications, can result in placental insufficiency and fetal growth restriction, though the linking causal mechanisms are unclear. We previously identified 11 gestationally-elevated maternal circulating miRNAs that predicted infant growth deficits following PAE. Here, we investigated whether these HEamiRNAs contribute to the pathology of PAE, by inhibiting trophoblast epithelial-mesenchymal transition (EMT), a pathway critical for placental development. We now report for the first time, that PAE inhibits expression of placental pro-EMT pathway members in both rodents and primates, and that HEamiRNAs collectively, but not individually, mediate placental EMT inhibition. HEamiRNAs collectively, but not individually, also inhibited cell proliferation and the EMT pathway in cultured trophoblasts, while inducing cell stress, and following trophoblast syncytialization, aberrant endocrine maturation. Moreover, a single intra-vascular administration of the pooled murine-expressed HEamiRNAs, to pregnant mice, decreased placental and fetal growth and inhibited expression of pro-EMT transcripts in placenta. Our data suggests that HEamiRNAs collectively interfere with placental development, contributing to the pathology of PAE, and perhaps also, to other causes of fetal growth restriction. SummaryMaternal gestational circulating microRNAs, predictive of adverse infant outcomes including growth deficits, following prenatal alcohol exposure, contribute to placental pathology by impairing the EMT pathway in trophoblasts.

developmental biology↗

bioRxiv2018

B1a cells protect against Schistosoma japonicum-induced liver inflammation and fibrosis by controlling monocyte infiltration

During Schistosoma infection, lack of B cells results in more severe granulomas, inflammation, and fibrosis in the liver, but the mechanisms underlying this pathology remain unclear. Thus, our aim was to clarify the mechanisms underpinning the immunomodulation of B cells in mice infected with Schistosoma japonicum. We found that B cell deficiency led to aggravated liver pathology, as demonstrated by increases in the size of the egg-associated granulomas, alanine transaminase levels, and collagen deposition. Compared with infected wild-type mice, infected B cell-deficient MT mice showed increased infiltration of Ly6Chi monocytes and higher levels of proinflammatory cytokines (tumor necrosis factor alpha, interleukin 6, and interleukin 12) and chemokines ([C-C motif] ligands (CCL)2, CCL3, CCL4, and CCL5). The results of flow cytometric analysis and cell transfer experiments showed that B1a cells increased significantly in the liver following S. japonicum infection, with some of those cells deriving from the peritoneal cavity. We also found that secretion of IL-10 from hepatic B cells increased significantly in infected wild-type mice and that this IL-10 was mainly derived from B1a cells. In addition, adoptively transferring peritoneal cavity B cells purified from wild-type, but not from IL-10-deficient mice, to MT mice significantly reduced liver pathology and liver infiltration of Ly6Chi monocytes. These reductions were accompanied by decreases in the expression levels of chemokines and inflammatory cytokines. Taken together, these data indicated that after S. japonicum infection, an increased number of hepatic B1a cells secrete IL-10, which inhibits the expression of chemokines and cytokines and suppresses the infiltration of Ly6Chi monocytes into the liver thereby alleviating liver early inflammation and late fibrosis. Understanding this immunomodulatory role of B1a cells in schistosomiasis may lead to the development of therapeutic strategies for Schistosoma-induced liver disease.\n\nAuthor summaryInfection with Schistosoma, a waterborne parasitic flatworm (trematode) commonly called a blood fluke, results in strong granulomatous inflammation caused by the deposition of eggs in the liver. A granuloma is a substantial immune cell infiltration around the eggs intermixed with liver cells that can protect the host against liver damage. However, excessive infiltration and inflammation can lead to severe liver injury and fibrosis. Here, we found that B1a cells accumulate in the liver of mice after S. japonicum-induced infection and that these B1a cells release the anti-inflammatory cytokine interleukin 10 to regulate inflammation. The B1a cell-derived interleukin 10 inhibits the expression of chemokines (which attract cells such as monocytes to sites of infection or inflammation) and thus restrains excessive infiltration of Ly6Chi monocytes (which may have proinflammatory activity) into the liver, thereby alleviating early inflammation and later fibrosis. Our study provides insight into the immunomodulation of B1a cells in schistosomiasis and offers key information for the development of therapeutic strategies in Schistosoma-induced liver disease.

immunology↗

bioRxiv2018

Alteration of Vascular Endothelial Cadherin in Alzheimer’s Disease Patient and Mouse Model

Alzheimers disease (AD) is characterized by amyloid plaques and pathologic cerebrovascular remodeling. Cerebrovascular abnormalities may contribute to the pathology of AD, but the molecular mechanisms are not fully understood. In this study, we evaluated blood-brain barrier (BBB) disruption and the role of VE-cadherin in the progression of amyloid pathology. Here, we determined that levels of VE-cadherin are decreased in brain vessels of AD patients and mouse model of AD. In vitro experiments showed that the disappearance of VE-cadherin by beta-amyloid at the endothelial cell surface was due to cleavage of VE-cadherin. VE-cadherin cleavage was inhibited by a {gamma}-secretase and ADAM10 inhibitor. The disappearance of VE-cadherin in brain vessels was also seen in amyloid precursor protein transgenic mice. In the postmortem brain of individuals with AD, furthermore, levels of VE-cadherin were significantly reduced in vessels. Dementia patients showed a distinct blood biochemical profile characterized by high soluble VE-cadherin (sVEC). There was a strong association between plasma sVEC (adjusted odds ratio = 3.41, P < 0.001) and dementia. These results suggest that measurements of plasma VE-cadherin could have the potential for predicting the risk of progressive AD.

neuroscience↗

bioRxiv2018

Anemia Diagnosis on a Simple Paper-based Assay

In developing countries, the maternal and neonatal mortality rate is often affected by prenatal period anemia, a preventable and ubiquitous impairment attributed due to low hemoglobin (Hgb) concentration. We report the development of a simple, frugal (~ 0.02 $ per test), rapid and high fidelity paper-based colorimetric microfluidic device for point-of-care (POC) detection of anemia. We validate our findings with 32 blood samples collected from different patients covering a wide spectrum of anemia and subsequently, compare with standard pathological results measured using a hematology analyzer. POC based Hgb estimates are correlated with the pathological gold standard estimates of Hgb levels (r = 0.909), and the POC test method yielded similar sensitivity and specificity for detecting mild anemia (n = 8) (<11 g/dl) (sensitivity: 87.5%, specificity: 100 %) and for severe anemia (n = 3) (<7 g/dl) (sensitivity: 100 %, specificity: 100 %). The estimated Hgb levels are, within 1.5 g/dl from the pathological estimate, for 91 % of the blood samples. Results demonstrate the elevated efficacy and viability of this POC colorimetric diagnostic test, in comparison to the state-of-the-art complex and expensive diagnostic tests for anemia detection.

bioengineering↗

bioRxiv2016

Disrupted cholinergic modulation can underlie abnormal gamma rhythms in the schizophrenia and and auditory hallucination

The pathophysiology of auditory hallucination, a common symptom of schizophrenia, has yet been understood, but during auditory hallucination, primary auditory cortex (A1) shows paradoxical responses. When auditory stimuli are absent, A1 becomes hyperactive, while A1 responses to auditory stimuli are reduced. Such activation pattern of A1 responses during auditory hallucination is consistent with aberrant gamma rhythms in schizophrenia observed during auditory tasks, raising the possibility that the pathology underlying abnormal gamma rhythms can account for auditory hallucination. Moreover, A1 receives top-down signals in the gamma frequency band from an adjacent association area (Par2), and cholinergic modulation regulates interactions between A1 and Par2. In this study, we utilized a computational model of A1 to ask if disrupted cholinergic modulation could underlie abnormal gamma rhythms in schizophrenia. Furthermore, based on our simulation results, we propose potential pathology by which A1 can directly contribute to auditory hallucination.

Pathology↗

bioRxiv2017

Rats and axolotls share a common molecular signature after spinal cord injury enriched in collagen-1

Spinal cord injury (SCI) in mammals leads to irreversible tissue damage and loss of function. In contrast, axolotls are able to regenerate scar-free the injured spinal cord. To explore new pathological mechanisms, we compared rat versus axolotl transcriptomics and isolated genes shared between species post-SCI. Unexpectedly, multiple transcripts involved in extracellular matrix remodelling, in particular collagen-1, were upregulated in both species after SCI. Proteomics validated persistent expression of the collagen-enriched matrix signature at the protein level. Collagen-1 accumulated in early and advanced rat lesions. Importantly, collagen-1 was likely associated with pathological vascular remodelling rather than classic fibrosis and the transcription factor SP1 was predicted and validated to regulate, at least in part, the expression of collagen-1 in rat lesions.

pathology↗

bioRxiv2018

Enhanced β-secretase processing of amyloid precursor protein in the skeletal muscle of ALS animal models

Amyotrophic lateral sclerosis (ALS) is a lethal neurodegenerative disorder primarily characterized by motor neuron degeneration and muscle paralysis. Several studies indicate that pathological changes in the skeletal muscle contribute to disease progression. We report a significant increase of {beta}-secretase processing of amyloid precursor protein (APP) in the skeletal muscle but not the spinal cord or cerebral cortex of hSOD1 (G93A) transgenic ALS mouse models. Enhanced {beta}-secretase processing of APP was manifested by up-regulated expression of {beta}CTF, the 22-kd CTF of APP, and {beta}-secretase processing enzyme, BACE1. Morphological analysis demonstrated that enhanced {beta}-secretase processing of APP mainly occurred in the atrophic myofibers of ALS mice. We also observed a similar change in APP processing in an hSOD1 (G93A) transgenic ALS pig model, suggesting that enhanced {beta}-secretase processing of APP in skeletal muscle may be a common pathological feature of ALS. These findings reveal a selective change in APP processing in skeletal muscle of ALS animal models, and highlight the involvement of aberrant APP processing in ALS pathogenesis.

pathology↗

bioRxiv2018

Deep learning based retrieval system for gigapixel histopathology cases and open access literature

Clinical practice is getting increasingly stressful for pathologists due to increasing complexity and time constraints. Histopathology is slowly shifting to digital pathology, thus creating opportunities to allow pathologists to improve reading quality or save time using Artificial Intelligence (AI)-based applications. We aim to enhance the practice of pathologists through a retrieval system that allows them to simplify their workflow, limit the need for second opinions, while also learning in the process. In this work, an innovative retrieval system for digital pathology is integrated within a Whole Slide Image (WSI) viewer, allowing to define regions of interest in images as queries for finding visually similar areas using deep representations. The back-end similarity computation algorithms are based on a multimodal approach, allowing to exploit both text information and content-based image features. Shallow and deep representations of the images were evaluated, the later showed a better overall retrieval performance in a set of 112 whole slide images from biopsies. The system was also tested by pathologists, highlighting its capabilities and suggesting possible ways to improve it and make it more usable in clinical practice. The retrieval system developed can enhance the practice of pathologists by enabling them to use their experience and knowledge to properly control artificial intelligence tools for navigating repositories of images for decision support purposes.

pathology↗

bioRxiv2015

A novel method to enhance the sensitivity of marker detection using a refined hierarchical prior of tissue similarities

MotivationIdentification of biochemical processes that drive the transformation of a totipotent cell into various cell types is essential to our understanding of living systems. This complex machinery determines how tissues differ in terms of their anatomy, physiology, morphology, and, more importantly, how various cellular control mechanisms contribute to the observed similarities/ differences. Tissue-selective genes orchestrate various aspects of cellular machinery in different tissues, and are known to be implicated in a number of tissue-specific pathologies.\n\nResultsWe propose a novel statistical approach that identifies and removes the effect of universally expressed genes in groups of tissues. This allows us to better characterize tissue similarities, as well as to identify tissue-selective genes. We use our method to construct a reliable hierarchy of tissue similarities. The groupings of tissues in this hierarchy are used to specify successively refined priors for identifying tissue-selective functions and their corresponding genes in the reduced subspace. We show that our refinement process enhances the signal-to-noise ratio in the identification of markers. Using case studies of immune cells and brain tissues, we show that our approach significantly outperforms the state-of-the-art methods, both in terms of coverage and reliability of the predicted tissue-selective genes.\n\nConclusionsOur statistical approach provides a general framework for enhancing the sensitivity of marker detection methods, which can be used in conjunction with other techniques. Even in cases where the number of available expression datasets is limited, we show that our marker detection method outperforms existing techniques. We present detailed validation on immune cells and brain tissues in this paper. Our approach can be applied to construct similar datasets of other human tissues as well, for identifying tissue-specific genes. We demonstrate how these tissue-selective genes enhance our understanding of differentiating biochemical features of brain tissues, shed light on how tissue-selective pathologies progress, and help us identify specific biomarkers and targets for future interventions.

Systems Biology↗

bioRxiv2015

Diagnostic Assessment of Osteosarcoma Chemoresistance Based on Virtual Clinical Trials

Osteosarcoma is the most common primary bone tumor in pediatric and young adult patients. Successful treatment of osteosarcomas requires a combination of surgical resection and systemic chemotherapy, both neoadjuvant (prior to surgery) and adjuvant (after surgery). The degree of necrosis following neoadjuvant chemotherapy correlates with the subsequent probability of disease-free survival. Tumors with less than 10% of viable cells after treatment represent patients with a more favorable prognosis. However, being able to predict early, such as at the time of the pre-treatment tumor biopsy, how the patient will respond to the standard chemotherapy would provide an opportunity for more personalized patient care. Patients with unfavorable predictions could be studied in a protocol, rather than a standard setting, towards improving therapeutic success. The onset of necrotic cells in osteosarcomas treated with chemotherapeutic agents is a measure of tumor sensitivity to the drugs. We hypothesize that the remaining viable cells, i.e., cells that have not responded to the treatment, are chemoresistant, and that the pathological characteristics of these chemoresistant tumor cells within the osteosarcoma pre-treatment biopsy can predict tumor response to the standard-of-care chemotherapeutic treatment. This hypothesis can be tested by comparing patient histopathology samples before, as well as after treatment to identify both morphological and immunochemical cellular features that are characteristic of chemoresistant cells, i.e., cells that survived treatment. Consequently, using computational simulations of dynamic changes in tumor pathology under the simulated standard of care chemotherapeutic treatment, one can couple the pre- and post-treatment morphological and spatial patterns of chemoresistant cells, and correlate them with patient clinical diagnoses. This procedure, that we named Virtual Clinical Trials, can serve as a potential predictive biomarker providing a novel value added decision support tool for oncologists.

Systems Biology↗

bioRxiv2015

Untangling cortico-striatal connectivity and cross-frequency coupling in L-DOPA-induced dyskinesia

We simultaneously recorded local field potentials in the primary motor cortex and sensorimotor striatum in awake, freely behaving, 6-OHDA lesioned hemi-parkinsonian rats in order to study the features directly related to pathological states such as parkinsonian state and levodopa-induced dyskinesia. We analysed the spectral characteristics of the obtained signals and observed that during dyskinesia the most prominent feature was a relative power increase in the high gamma frequency range at around 80 Hz, while for the parkinsonian state it was in the beta frequency range. Here we show that during both pathological states effective connectivity in terms of Granger causality is bidirectional with an accent on the striatal influence on the cortex. In the case of dyskinesia, we also found a high increase in effective connectivity at 80 Hz. In order to further understand the 80- Hz phenomenon, we performed cross-frequency analysis and observed characteristic patterns in the case of dyskinesia but not in the case of the parkinsonian state or the control state. We noted a large decrease in the modulation of the amplitude at 80 Hz by the phase of low frequency oscillations (up to ~10 Hz) across both structures in the case of dyskinesia. This may suggest a lack of coupling between the low frequency activity of the recorded network and the group of neurons active at ~80 Hz.

Neuroscience↗

bioRxiv2016

Cellular aspects of gonadal atrophy in P-M hybrid dysgenesis

Gonadal atrophy is the most typical and dramatic manifestation of intraspecific hybrid dysgenesis syndrome leading to sterility of Drosophila melanogaster dysgenic progeny. The P-M system of hybrid dysgenesis is primarily associated with germ cell degeneration during the early stages of Drosophila development at elevated temperatures. In the present study, we have defined the phase of germ cell death as beginning at the end of embryogenesis immediately following gonad formation. The early stages of germ cell formation in dysgenic flies showed sensitivity to developmental temperature increases at any stage of the Drosophila life cycle including the imago. Analysis of germ cell reactions to hybrid dysgenesis induction revealed significant changes in subcellular structure, especially mitochondria, prior to germ cell breakdown. The mitochondrial pathology can be the reason for the activation of cell death pathways in dysgenic germ cells and lead to gonadal atrophy.\n\nSummaryWe investigated the hybrid dysgenesis in the context of germ cell development and observed the dysgenic effect is associated with dramatic pathological changes in structure of germ cell mitochondria and lead to massive and quick cell death. The temperature-dependent screening of germ cells developmental pattern in dysgenic background showed that these cells are susceptible to the hybrid dysgenesis at any drosophila life-cycle stage, including in the imago.

Developmental Biology↗

bioRxiv2016

Hierarchical cortical transcriptome disorganization in autism

BackgroundAutism spectrum disorders (ASD) are etiologically heterogeneous and complex. Functional genomics work has begun to identify a diverse array of dysregulated transcriptomic programs (e.g., synaptic, immune, cell cycle, DNA damage, WNT signaling, cortical patterning and differentiation) potentially involved in ASD brain abnormalities during childhood and adulthood. However, it remains unclear whether such diverse dysregulated pathways are independent of each other or instead reflect coordinated hierarchical systems-level pathology.\n\nMethodsTwo ASD cortical transcriptome datasets were re-analyzed using consensus weighted gene co-expression network analysis (WGCNA) to identify common coexpression modules across datasets. Linear mixed-effect models and Bayesian replication statistics were used to identify replicable differentially expressed modules. Eigengene network analysis was then utilized to identify between-group differences in how co-expression modules interact and cluster into hierarchical meta-modular organization. Protein-protein interaction analyses were also used to determine whether dysregulated co-expression modules show enhanced interactions.\n\nResultsWe find replicable evidence for 10 gene co-expression modules that are differentially expressed in ASD cortex. Rather than being independent non-interacting sources of pathology, these dysregulated co-expression modules work in synergy and physically interact at the protein level. These systems-level transcriptional signals are characterized by downregulation of synaptic processes coordinated with upregulation of immune/inflammation, response to other organism, catabolism, viral processes, translation, protein targeting and localization, cell proliferation, and vasculature development. Hierarchical organization of meta-modules (clusters of highly correlated modules) is also highly affected in ASD.\n\nConclusionsThese findings highlight that dysregulation of the ASD cortical transcriptome is characterized by the dysregulation of multiple coordinated transcriptional programs producing synergistic systems-level effects that cannot be fully appreciated by studying the individual component biological processes in isolation.

Genomics↗

bioRxiv2016

Quantifying Differences and Similarities in Whole-brain White Matter Architecture Using Local Connectome Fingerprints

Quantifying differences or similarities in connectomes has been a challenge due to the immense complexity of global brain networks. Here we introduce a noninvasive method that uses diffusion MRI to characterize whole-brain white matter architecture as a single local connectome fingerprint that allows for a direct comparison between structural connectomes. In four independently acquired data sets with repeated scans (total N=213), we show that the local connectome fingerprint is highly specific to an individual, allowing for an accurate self-versus-others classification that achieved 100% accuracy across 17,398 identification tests. The estimated classification error was approximately one thousand times smaller than fingerprints derived from diffusivity-based measures or region-to-region connectivity patterns. The local connectome fingerprint also revealed neuroplasticity within an individual reflected as a decreasing trend in self-similarity across time, whereas this change was not observed in the diffusivity measures. Moreover, the local connectome fingerprint can be used as a phenotypic marker, revealing 12.51% similarity between monozygotic twins, 5.14% between dizygotic twins, and 4.51% between none-twin siblings. This novel approach opens a new door for probing the influence of pathological, genetic, social, or environmental factors on the unique configuration of the human connectome.\n\nAuthor SummaryThe local organization of white matter architecture is highly unique to individuals, making it a tangible metric of connectomic differences. The variability in local white matter architecture is found to be partially determined by genetic factors, but largely plastic across time. This approach opens a new door for probing the influence of pathological, genetic, social, or environmental factors on the unique configuration of the human connectome.

Neuroscience↗

bioRxiv2016

Inferring intrinsic and extrinsic noise from a dual fluorescent reporter

Dual fluorescent reporter constructs, which measure gene expression from two identical promoters within the same cell, allow total gene expression noise to be decomposed into an extrinsic component, roughly associated with cell-to-cell fluctuations in cellular component concentrations, and intrinsic noise, roughly associated with inherent stochasticity of the biochemical reactions involved in gene expression [1]. A recent paper by Fu and Pachter presented frequentist statistical estimators for intrinsic and extrinsic noise using data from dual reporters [2]. For comparison, I here present results of a Bayesian analysis of this problem. I show that the orthodox estimators suffer from pathologies such as predicting negative values for a manifestly non-negative quantity, i.e. variance, and show that the Bayesian estimators do not suffer from such pathologies. In addition, I show that the Bayesian analysis automatically identifies that optimal estimates of intrinsic and extrinsic noise depend on a subtle combination of two statistics of the data, allowing for accuracies that are up to twice the accuracy of the orthodox estimators in some parameter regimes.\n\nI hope up this little worked out example contrasting orthodox statistical analysis based on ad hoc estimators with estimators resulting from a Bayesian analysis, will be educational for others in the field. I distribute a Mathematica Notebook with this paper that allows users to easily reproduce all results and figures of the paper.

Bioinformatics↗

bioRxiv2016

Learning from critical care management of sheep receiving extra-corporeal membrane oxygenation for smoke-induced acute lung injury as a tool for processing large clinical datasets

BackgroundNumerous successful therapies developed for human medicine involve animal experimentation. Animal studies that are focused solely on translational potential, may not sufficiently document unexpected outcomes. Considerable amounts of data from such studies could be used to advance veterinary science. For example, sheep are increasingly being used as models of intensive care and therefore, data arising from such models must be published. In this study, the hypothesis is that there is little information describing cardiorespiratory physiological data from sheep models of intensive care and the author aimed to analyse such data to provide biological information that is currently not available for sheep that received extracorporeal life support (ECLS) following acute smoke-induced lung injury. MethodsNineteen mechanically ventilated adult ewes undergoing intensive care during evaluation of a form of ECLS (treatment) for acute lung injury were used to collate clinical observations. Eight sheep were injured by acute smoke inhalation prior to treatment (injured/treated), while another eight were not injured but treated (uninjured/treated). Two sheep were injured but not treated (injured/untreated), while one received room air instead of smoke as the injury and was not treated (placebo/untreated). The data were then analysed for 11 physiological categories and compared between the two treated groups. ResultsCompared with the baseline, treatment contributed to and exacerbated the deterioration of pulmonary pathology by reducing lung compliance and the arterial oxygen partial pressure to fractional inspired oxygen (PaO2/FiO2) ratio. The oxygen extraction index changes mirrored those of the PaO2/FiO2 ratio. Decreasing coronary perfusion pressure predicted the severity of cardiopulmonary injury. ConclusionsThese novel observations could help in understanding similar pathology such as that which occurs in animal victims of smoke inhalation from house or bush fires, aspiration pneumonia secondary to tick paralysis and in the management of the severe coronavirus disease 2019 (COVID-19) in humans.

Scientific Communication and Education↗