339 results found
Becker C, Hardarson J, Hoelzer A, et al., 2023, Evaluation of cervical lymph nodes using multispectral optoacoustic tomography: a proof-of-concept study., Eur Arch Otorhinolaryngol, Vol: 280, Pages: 4657-4664
OBJECTIVES: Examination of lymph nodes is one of the most common indications for imaging in the head and neck region. The purpose of this study is to evaluate whether multispectral optoacoustic tomography can be used to observe chromophore differences between benign and malignant neck lymph nodes. MATERIALS AND METHODS: Proof-of-concept ex vivo study of resected cervical lymph nodes from 11 patients. The examination of lymph nodes included imaging with hybrid ultrasound and multispectral tomography system followed by spectral unmixing to separate signals from the endogenous chromophores water, lipid, hemoglobin and oxygenated hemoglobin; calculation of semi-quantitative parameters (total hemoglobin and relative oxygenation of hemoglobin). Comparison of the results from the hybrid measurement with the histopathological results. RESULTS: Most patients suffered from squamous cell carcinoma (n = 7), also metastasis from salivary gland adenocarcinoma and papillary thyroid carcinoma, were included. The comparison between benign cervical lymph nodes and metastases showed significant differences for the absorbers water, lipid, hemoglobin and oxygenated hemoglobin and total hemoglobin. CONCLUSIONS: Our ex vivo study suggests that multispectral optoacoustic tomography can be used to detect differences between reactive lymph nodes and metastases. The measurement of endogenous chromophores can be used for this purpose. The examinations are non-invasively and thus potentially improve diagnostic prediction. However, potential influences from the ex vivo setting must be considered.
Simon-Chica A, Wülfers EM, Kohl P, 2023, Nonmyocytes as electrophysiological contributors to cardiac excitation and conduction., Am J Physiol Heart Circ Physiol, Vol: 325, Pages: H475-H491
Although cardiac action potential (AP) generation and propagation have traditionally been attributed exclusively to cardiomyocytes (CM), other cell types in the heart are also capable of forming electrically conducting junctions. Interactions between CM and nonmyocytes (NM) enable and modulate each other's activity. This review provides an overview of the current understanding of heterocellular electrical communication in the heart. Although cardiac fibroblasts were initially thought to be electrical insulators, recent studies have demonstrated that they form functional electrical connections with CM in situ. Other NM, such as macrophages, have also been recognized as contributing to cardiac electrophysiology and arrhythmogenesis. Novel experimental tools have enabled the investigation of cell-specific activity patterns in native cardiac tissue, which is expected to yield exciting new insights into the development of novel or improved diagnostic and therapeutic strategies.
Chiang C-J, Kim H, Jonson-Reid M, et al., 2023, Risk factors and neglect subtypes: Findings from a nationally representative data set., Am J Orthopsychiatry
Child neglect is a multidimensional concept encompassing various forms. Prior studies suggest that risk factors differ by neglect subtypes such as physical or supervisory neglect, but few studies address how risk factors vary between other neglect subtypes. This study aimed to examine how risk factors were related to neglect subtypes such as physical neglect, lack of supervision, exposure to domestic violence, substance-abusing parent, and mixed neglect. This study used secondary data from a nationally representative sample of children (National Survey of Child and Adolescent Well-Being-II, N = 5,872), and 786 children with a first-time child protective services investigation for neglect allegations alone were selected. Multinomial logistic regression analysis was used to explore how individual, family, and community risk factors may be associated with specific neglect subtypes. Five risk factors were able to discriminate between subtypes of neglect. For example, being a young child is associated with a greater risk of experiencing multiple forms of neglect. Caregiver's mental health problem is associated with a higher likelihood of being referred for multiple forms of neglect, particularly as compared with the risk of being referred for lack of supervision. Having poor social support is associated with a higher risk of physical neglect, and caregiver high stress is related to a higher risk of domestic violence. While most intervention programs target risk factors for overall child neglect, not specific neglect subtypes cases, our findings suggest that the intervention approach based on an understanding of the heterogeneity in risk factors between neglect subtypes is advisable. (PsycInfo Database Record (c) 2023 APA, all rights reserved).
Lother A, Kohl P, 2023, The heterocellular heart: identities, interactions, and implications for cardiology., Basic Res Cardiol, Vol: 118
The heterocellular nature of the heart has been receiving increasing attention in recent years. In addition to cardiomyocytes as the prototypical cell type of the heart, non-myocytes such as endothelial cells, fibroblasts, or immune cells are coming more into focus. The rise of single-cell sequencing technologies enables identification of ever more subtle differences and has reignited the question of what defines a cell's identity. Here we provide an overview of the major cardiac cell types, describe their roles in homeostasis, and outline recent findings on non-canonical functions that may be of relevance for cardiology. We highlight modes of biochemical and biophysical interactions between different cardiac cell types and discuss the potential implications of the heterocellular nature of the heart for basic research and therapeutic interventions.
Darkow E, Yusuf D, Rajamani S, et al., 2023, Meta-Analysis of Mechano-Sensitive Ion Channels in Human Hearts: Chamber- and Disease-Preferential mRNA Expression., Int J Mol Sci, Vol: 24
The cardiac cell mechanical environment changes on a beat-by-beat basis as well as in the course of various cardiac diseases. Cells sense and respond to mechanical cues via specialized mechano-sensors initiating adaptive signaling cascades. With the aim of revealing new candidates underlying mechano-transduction relevant to cardiac diseases, we investigated mechano-sensitive ion channels (MSC) in human hearts for their chamber- and disease-preferential mRNA expression. Based on a meta-analysis of RNA sequencing studies, we compared the mRNA expression levels of MSC in human atrial and ventricular tissue samples from transplant donor hearts (no cardiac disease), and from patients in sinus rhythm (underlying diseases: heart failure, coronary artery disease, heart valve disease) or with atrial fibrillation. Our results suggest that a number of MSC genes are expressed chamber preferentially, e.g., CHRNE in the atria (compared to the ventricles), TRPV4 in the right atrium (compared to the left atrium), CACNA1B and KCNMB1 in the left atrium (compared to the right atrium), as well as KCNK2 and KCNJ2 in ventricles (compared to the atria). Furthermore, 15 MSC genes are differentially expressed in cardiac disease, out of which SCN9A (lower expressed in heart failure compared to donor tissue) and KCNQ5 (lower expressed in atrial fibrillation compared to sinus rhythm) show a more than twofold difference, indicative of possible functional relevance. Thus, we provide an overview of cardiac MSC mRNA expression in the four cardiac chambers from patients with different cardiac diseases. We suggest that the observed differences in MSC mRNA expression may identify candidates involved in altered mechano-transduction in the respective diseases.
Bailey DM, Berg RMG, Stewart A, et al., 2023, Sharpey-Schafer, Langley and Sherrington: 'swordsmen' of physiology. A historical look to the future, EXPERIMENTAL PHYSIOLOGY, ISSN: 0958-0670
Kubo Y, Kohl P, 2023, Congratulations, celebrations, invitations!, JOURNAL OF PHYSIOLOGY-LONDON, Vol: 601, Pages: 1047-1047, ISSN: 0022-3751
Karoutas A, Szymanski W, Rausch T, et al., 2023, The NSL complex maintains nuclear architecture stability via lamin A/C acetylation (vol 21, pg 1248, 2019), NATURE CELL BIOLOGY, ISSN: 1465-7392
Cameron BA, Kohl P, Quinn TA, 2023, Cellular and Subcellular Mechanisms of Ventricular Mechano-Arrhythmogenesis, Cardiac and Vascular Biology, Pages: 265-298
Intrinsic regulation of cardiac electrical and mechanical activity allows the heart to adjust its function to meet the metabolic demand of the body. This includes the acute feedback of cardiac mechanics to electrics (‘mechano-electric coupling’, MEC), which is achieved primarily through cellular and subcellular elements, including mechano-sensitive ion channels, biophysical signal transmitters and mechano-sensitive biochemical signalling pathways. While MEC is normally involved in fine-tuning of cardiac function, in disease states characterised by perturbations in the cardiac mechanical environment, myocardial mechanics or elements of MEC, it can instead drive arrhythmogenic changes in electrophysiology (‘mechano-arrhythmogenesis’), which can result in sustained ventricular tachyarrhythmias. This chapter briefly reviews essential aspects of MEC, discusses clinical evidence and experimental studies of ventricular mechano-arrhythmogenesis and describes the underlying cellular and subcellular elements involved. It then puts mechano-arrhythmogenesis into a clinical context by focussing on two pathological states that highlight the spatio-temporal dependence of mechano-arrhythmogenesis in the whole heart: one that is characterised by acute, local changes in cardiac electro-mechanics and MEC (acute regional myocardial ischaemia) and one that involves chronic, global changes (hypertension). Overall, an improved understanding of the mechanisms driving ventricular mechano-arrhythmogenesis is critical for the development of anti-arrhythmic therapies targeting MEC, such as modulation of tissue mechanics or alteration of subcellular mechano-sensitive components.
Kohl P, Zgierski-Johnston CM, 2023, Assessment of Tissue Viability by Functional Imaging of Membrane Potential., Methods Mol Biol, Vol: 2644, Pages: 423-434
Electrical activity plays a key role in physiology, in particular for signaling and coordination. Cellular electrophysiology is often studied with micropipette-based techniques such as patch clamp and sharp electrodes, but for measurements at the tissue or organ scale, more integrated approaches are needed. Epifluorescence imaging of voltage-sensitive dyes ("optical mapping") is a tissue non-destructive approach to obtain insight into electrophysiology with high spatiotemporal resolution. Optical mapping has primarily been applied to excitable organs, especially the heart and brain. Action potential durations, conduction patterns, and conduction velocities can be determined from the recordings, providing information about electrophysiological mechanisms, including factors such as effects of pharmacological interventions, ion channel mutations, or tissue remodeling. Here, we describe the process for optical mapping of Langendorff-perfused mouse hearts, highlighting potential issues and key considerations.
Chleilat E, Walz TP, Kohl P, et al., 2022, New insights into reperfusion arrhythmia mechanism and means to circumvent perivascular excitation tunnelling-based rhythm disturbance, Publisher: ELSEVIER SCI LTD, Pages: S25-S26, ISSN: 0022-2828
Kohl P, 2022, Opinion matters, JOURNAL OF PHYSIOLOGY-LONDON, Vol: 600, Pages: 5169-5169, ISSN: 0022-3751
Peyronnet R, Desai A, Edelmann J-C, et al., 2022, Simultaneous assessment of radial and axial myocyte mechanics by combining atomic force microscopy and carbon fibre techniques., Philos Trans R Soc Lond B Biol Sci, Vol: 377
Cardiomyocytes sense and shape their mechanical environment, contributing to its dynamics by their passive and active mechanical properties. While axial forces generated by contracting cardiomyocytes have been amply investigated, the corresponding radial mechanics remain poorly characterized. Our aim is to simultaneously monitor passive and active forces, both axially and radially, in cardiomyocytes freshly isolated from adult mouse ventricles. To do so, we combine a carbon fibre (CF) set-up with a custom-made atomic force microscope (AFM). CF allows us to apply stretch and to record passive and active forces in the axial direction. The AFM, modified for frontal access to fit in CF, is used to characterize radial cell mechanics. We show that stretch increases the radial elastic modulus of cardiomyocytes. We further find that during contraction, cardiomyocytes generate radial forces that are reduced, but not abolished, when cells are forced to contract near isometrically. Radial forces may contribute to ventricular wall thickening during contraction, together with the dynamic re-orientation of cells and sheetlets in the myocardium. This new approach for characterizing cell mechanics allows one to obtain a more detailed picture of the balance of axial and radial mechanics in cardiomyocytes at rest, during stretch, and during contraction. This article is part of the theme issue 'The cardiomyocyte: new revelations on the interplay between architecture and function in growth, health, and disease'.
Quinn TA, Kohl P, 2022, The Bainbridge effect: stretching our understanding of cardiac pacemaking for more than a century, JOURNAL OF PHYSIOLOGY-LONDON, Vol: 600, Pages: 4377-4379, ISSN: 0022-3751
Giardini F, Olianti C, Biasci V, et al., 2022, Correlating electrical dysfunctions and structural remodeling in Arrhythmogenic Mouse Hearts by advanced optical methods, Publisher: OXFORD UNIV PRESS, ISSN: 0008-6363
Emig R, Hoess P, Cai H, et al., 2022, Benchmarking of Cph1 Mutants and DrBphP for Light-Responsive Phytochrome-Based Hydrogels with Reversibly Adjustable Mechanical Properties, ADVANCED BIOLOGY, Vol: 6, ISSN: 2701-0198
Kohl P, Greiner J, Rog-Zielinska EA, 2022, Electron microscopy of cardiac 3D nanodynamics: form, function, future, NATURE REVIEWS CARDIOLOGY, Vol: 19, Pages: 607-619, ISSN: 1759-5002
Khokhlova A, Solovyova O, Kohl P, et al., 2022, Single cardiomyocytes from papillary muscles show lower preload-dependent activation of force compared to cardiomyocytes from the left ventricular free wall, JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY, Vol: 166, Pages: 127-136, ISSN: 0022-2828
Kohl P, 2022, Ask not what The Journal can do for you, JOURNAL OF PHYSIOLOGY-LONDON, Vol: 600, Pages: 1537-1538, ISSN: 0022-3751
Duerschmied D, Hilgendorf I, Kohl P, et al., 2022, SFB1425-The heterocellular nature of cardiac lesions: Identities, interactions, implications, KARDIOLOGIE, Vol: 16, Pages: 128-135, ISSN: 2731-7129
Rog-Zielinska EA, Kohl P, 2022, Cardiomyocyte t-tubular fluid pumping, Publisher: CELL PRESS, Pages: 155A-155A, ISSN: 0006-3495
Simon-Chica A, Fernandez MC, Wuelfers EM, et al., 2022, Novel insights into the electrophysiology of murine cardiac macrophages: relevance of voltage-gated potassium channels, Cardiovascular Research, Vol: 118, Pages: 798-813, ISSN: 0008-6363
AimsMacrophages (MΦ), known for immunological roles, such as phagocytosis and antigen presentation, have been found to electrotonically couple to cardiomyocytes (CM) of the atrioventricular node via Cx43, affecting cardiac conduction in isolated mouse hearts. Here, we characterize passive and active electrophysiological properties of murine cardiac resident MΦ, and model their potential electrophysiological relevance for CM.Methods and resultsWe combined classic electrophysiological approaches with 3D florescence imaging, RNA-sequencing, pharmacological interventions, and computer simulations. We used Cx3creYFP/+1 mice wherein cardiac MΦ are fluorescently labelled. FACS-purified fluorescent MΦ from mouse hearts were studied by whole-cell patch-clamp. MΦ electrophysiological properties include: membrane resistance 2.2±0.1 GΩ (all data mean±SEM), capacitance 18.3±0.1 pF, resting membrane potential −39.6±0.3 mV, and several voltage-activated, outward or inwardly rectifying potassium currents. Using ion channel blockers (barium, TEA, 4-AP, margatoxin, XEN-D0103, and DIDS), flow cytometry, immuno-staining, and RNA-sequencing, we identified Kv1.3, Kv1.5, and Kir2.1 as channels contributing to observed ion currents. MΦ displayed four patterns for outward and two for inward-rectifier potassium currents. Additionally, MΦ showed surface expression of Cx43, a prerequisite for homo- and/or heterotypic electrotonic coupling. Experimental results fed into development of an original computational model to describe cardiac MΦ electrophysiology. Computer simulations to quantitatively assess plausible effects of MΦ on electrotonically coupled CM showed that MΦ can depolarize resting CM, shorten early and prolong late action potential duration, with effects depending on coupling strength and individual MΦ electrophysiological properties, in particular resting membrane potential and presence/absence of
Greiner J, Schiatti T, Kaltenbacher W, et al., 2022, Consecutive-Day Ventricular and Atrial Cardiomyocyte Isolations from the Same Heart: Shifting the Cost-Benefit Balance of Cardiac Primary Cell Research, CELLS, Vol: 11
Muellenbroich MC, Kelly A, Acker C, et al., 2021, Novel Optics-Based Approaches for Cardiac Electrophysiology: A Review, FRONTIERS IN PHYSIOLOGY, Vol: 12
Yamaguchi Y, Allegrini B, Rapetti-Mauss R, et al., 2021, Hereditary Xerocytosis: Differential Behavior of PIEZO1 Mutations in the N-Terminal Extracellular Domain Between Red Blood Cells and HEK Cells, FRONTIERS IN PHYSIOLOGY, Vol: 12, ISSN: 1664-042X
Emig R, Zgierski-Johnston CM, Timmermann V, et al., 2021, Passive myocardial mechanical properties: meaning, measurement, models., Biophys Rev, Vol: 13, Pages: 587-610, ISSN: 1867-2450
Passive mechanical tissue properties are major determinants of myocardial contraction and relaxation and, thus, shape cardiac function. Tightly regulated, dynamically adapting throughout life, and affecting a host of cellular functions, passive tissue mechanics also contribute to cardiac dysfunction. Development of treatments and early identification of diseases requires better spatio-temporal characterisation of tissue mechanical properties and their underlying mechanisms. With this understanding, key regulators may be identified, providing pathways with potential to control and limit pathological development. Methodologies and models used to assess and mimic tissue mechanical properties are diverse, and available data are in part mutually contradictory. In this review, we define important concepts useful for characterising passive mechanical tissue properties, and compare a variety of in vitro and in vivo techniques that allow one to assess tissue mechanics. We give definitions of key terms, and summarise insight into determinants of myocardial stiffness in situ. We then provide an overview of common experimental models utilised to assess the role of environmental stiffness and composition, and its effects on cardiac cell and tissue function. Finally, promising future directions are outlined.
Abu Nahia K, Migdal M, Quinn TA, et al., 2021, Genomic and physiological analyses of the zebrafish atrioventricular canal reveal molecular building blocks of the secondary pacemaker region, Cellular and Molecular Life Sciences, Vol: 78, Pages: 6669-6687, ISSN: 1420-682X
The atrioventricular canal (AVC) is the site where key structures responsible for functional division between heart regions are established, most importantly, the atrioventricular (AV) conduction system and cardiac valves. To elucidate the mechanism underlying AVC development and function, we utilized transgenic zebrafish line sqet31Et expressing EGFP in the AVC to isolate this cell population and profile its transcriptome at 48 and 72 hpf. The zebrafish AVC transcriptome exhibits hallmarks of mammalian AV node, including the expression of genes implicated in its development and those encoding connexins forming low conductance gap junctions. Transcriptome analysis uncovered protein-coding and noncoding transcripts enriched in AVC, which have not been previously associated with this structure, as well as dynamic expression of epithelial-to-mesenchymal transition markers and components of TGF-β, Notch, and Wnt signaling pathways likely reflecting ongoing AVC and valve development. Using transgenic line Tg(myl7:mermaid) encoding voltage-sensitive fluorescent protein, we show that abolishing the pacemaker-containing sinoatrial ring (SAR) through Isl1 loss of function resulted in spontaneous activation in the AVC region, suggesting that it possesses inherent automaticity although insufficient to replace the SAR. The SAR and AVC transcriptomes express partially overlapping species of ion channels and gap junction proteins, reflecting their distinct roles. Besides identifying conserved aspects between zebrafish and mammalian conduction systems, our results established molecular hallmarks of the developing AVC which underlies its role in structural and electrophysiological separation between heart chambers. This data constitutes a valuable resource for studying AVC development and function, and identification of novel candidate genes implicated in these processes.
Ravens U, Kohl P, 2021, Mechanoelectric feedback in the human heart: A causal affair, HEART RHYTHM, Vol: 18, Pages: 1414-1415, ISSN: 1547-5271
Rog-Zielinska E, Kohl P, 2021, Nanoscopic t-tubular deformation during cardiac mechanical cycle, Publisher: SPRINGER, Pages: 45-45, ISSN: 0175-7571
Jakob D, Klesen A, Darkow E, et al., 2021, Heterogeneity and Remodeling of Ion Currents in Cultured Right Atrial Fibroblasts From Patients With Sinus Rhythm or Atrial Fibrillation, FRONTIERS IN PHYSIOLOGY, Vol: 12
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