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Intensive Care: Fundamental Aspects of Molecular Pathophysiology

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: closed (20 July 2023) | Viewed by 7838

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Special Issue Editors

Prof. Dr. Evgeny Grigoryev

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Guest Editor

Research Institute of Complex Problems of Cardiovascular Disease, Russian Academy of Medical Sciences, 650002 Kemerovo, Russia
Interests: sepsis; systemic inflammatory response; multiorgan failure; induced immunosuppression

Dr. Artem Kuzovlev

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Guest Editor

Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology, 107031 Moscow, Russia
Interests: multiorgan failure; cardiopulmonary resuscitation

Special Issue Information

Dear Colleagues,

A critical care patient is characterized by a combination of different types of hypoxia, the development of multiple organ failure and the difficulty in choosing methods of intensive care depending on the critical care phase. The main directions for studying the molecular mechanisms of the development of a critical care patient, systemic inflammation, intercellular signaling, and innate immunity can be effective in terms of selecting candidate biomarkers for diagnosing and predicting a critical condition.

Prof. Dr. Evgeny Grigoryev
Dr. Artem Kuzovlev
Guest Editors

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Keywords

critical care medicine
systemic inflammatory response
molecular mechanisms
intercellular signalig
innate mmunity
multiorgan failure
candidate biomarkers

Published Papers (4 papers)

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Research

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13 pages, 3794 KiB

Open AccessArticle

Assaying ADAMTS13 Activity as a Potential Prognostic Biomarker for Sinusoidal Obstruction Syndrome in Mice

by Masakazu Saeki, Seiichi Munesue, Yuri Higashi, Ai Harashima, Ryohei Takei, Satoshi Takada, Shinichi Nakanuma, Tetsuo Ohta, Shintaro Yagi, Hidehiro Tajima and Yasuhiko Yamamoto

Int. J. Mol. Sci. 2023, 24(22), 16328; https://doi.org/10.3390/ijms242216328 - 15 Nov 2023

Viewed by 1119

Abstract

Sinusoidal obstruction syndrome (SOS) is a serious liver disorder that occurs after liver transplantation, hematopoietic stem cell transplantation, and the administration of anticancer drugs. Since SOS is a life-threatening condition that can progress to liver failure, early detection and prompt treatment are required for the survival of patients with this condition. In this study, female CD1 mice were divided into treatment and control groups after the induction of an SOS model using monocrotaline (MCT, 270 mg/kg body weight intraperitoneally). The mice were analyzed at 0, 12, 24, and 48 h after MCT administration, and blood and liver samples were collected for assays and histopathology tests. SOS was observed in the livers 12 h after MCT injection. In addition, immunohistochemical findings demonstrated CD42b-positive platelet aggregations, positive signals for von Willebrand factor (VWF), and a disintegrin-like metalloproteinase with thrombospondin type 1 motifs 13 (ADAMTS13) in the MCT-exposed liver sinusoid. Although ADAMTS13’s plasma concentrations peaked at 12 h, its enzyme activity continuously decreased by 75% at 48 h and, inversely and proportionally, concentrations in the VWF-A2 domain, in which the cleavage site of ADAMTS13 is located, increased after MCT injection. These findings suggest that the plasma concentration and activity of ADAMTS13 could be useful biomarkers for early detection and therapeutic intervention in patients with SOS. Full article

(This article belongs to the Special Issue Intensive Care: Fundamental Aspects of Molecular Pathophysiology)

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21 pages, 16522 KiB

Open AccessArticle

Atomic Force Microscopy and High-Resolution Spectrophotometry for Study of Anoxemia and Normoxemia in Model Experiment In Vitro

by Elena Kozlova, Ekaterina Sherstyukova, Viktoria Sergunova, Andrey Grechko, Artem Kuzovlev, Snezhanna Lyapunova, Vladimir Inozemtsev, Aleksandr Kozlov and Aleksandr Chernysh

Int. J. Mol. Sci. 2023, 24(13), 11043; https://doi.org/10.3390/ijms241311043 - 3 Jul 2023

Cited by 4 | Viewed by 1268

Abstract

The oxygen content in the blood may decrease under the influence of various physicochemical factors and different diseases. The state of hypoxemia is especially dangerous for critically ill patients. In this paper, we describe and analyze the changes in the characteristics of red blood cells (RBCs) with decreasing levels of oxygen in the RBC suspension from normoxemia to hypoxemia/anoxemia in an in vitro model experiment. The RBCs were stored in hypoxemia/anoxemia and normoxemia conditions in closed and open tubes correspondingly. For the quantitative study of RBC parameter changes, we used atomic force microscopy, digital spectrophotometry, and nonlinear curve fitting of the optical spectra. In both closed and open tubes, at the end of the storage period by day 29, only 2% of discocytes remained, and mainly irreversible types, such as microspherocytes and ghosts, were observed. RBC hemolysis occurred at a level of 25–30%. Addition of the storage solution, depending on the concentration, changed the influence of hypoxemia on RBCs. The reversibility of the change in hemoglobin derivatives was checked. Based on the experimental data and model approach, we assume that there is an optimal level of hypoxemia at which the imbalance between the oxidative and antioxidant systems, the rate of formation of reactive oxygen species, and, accordingly, the disturbances in RBCs, will be minimal. Full article

(This article belongs to the Special Issue Intensive Care: Fundamental Aspects of Molecular Pathophysiology)

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14 pages, 1221 KiB

Open AccessArticle

Optimizing Fluid Management Guided by Volumetric Parameters in Patients with Sepsis and ARDS

by Evgeniia V. Fot, Natalia O. Khromacheva, Aleksei A. Ushakov, Aleksei A. Smetkin, Vsevolod V. Kuzkov and Mikhail Y. Kirov

Int. J. Mol. Sci. 2023, 24(10), 8768; https://doi.org/10.3390/ijms24108768 - 15 May 2023

Viewed by 1988

Abstract

We compared two de-escalation strategies guided by either extravascular lung water or global end-diastolic volume-oriented algorithms in patients with sepsis and ARDS. Sixty patients with sepsis and ARDS were randomized to receive de-escalation fluid therapy, guided either by the extravascular lung water index (EVLWI, n = 30) or the global end-diastolic volume index (GEDVI, n = 30). In cases of GEDVI > 650 mL/m² or EVLWI > 10 mL/kg, diuretics and/or controlled ultrafiltration were administered to achieve the cumulative 48-h fluid balance in the range of 0 to −3000 mL. During 48 h of goal-directed de-escalation therapy, we observed a decrease in the SOFA score (p < 0.05). Extravascular lung water decreased only in the EVLWI-oriented group (p < 0.001). In parallel, PaO₂/FiO₂ increased by 30% in the EVLWI group and by 15% in the GEDVI group (p < 0.05). The patients with direct ARDS demonstrated better responses to dehydration therapy concerning arterial oxygenation and lung fluid balance. In sepsis-induced ARDS, both fluid management strategies, based either on GEDVI or EVLWI, improved arterial oxygenation and attenuated organ dysfunction. The de-escalation therapy was more efficient for direct ARDS. Full article

(This article belongs to the Special Issue Intensive Care: Fundamental Aspects of Molecular Pathophysiology)

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Review

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34 pages, 9398 KiB

Open AccessReview

Glucocorticoid Treatment in Acute Respiratory Distress Syndrome: An Overview on Mechanistic Insights and Clinical Benefit

by Jinquan Zhang, Peng Ge, Jie Liu, Yalan Luo, Haoya Guo, Guixin Zhang, Caiming Xu and Hailong Chen

Int. J. Mol. Sci. 2023, 24(15), 12138; https://doi.org/10.3390/ijms241512138 - 28 Jul 2023

Cited by 4 | Viewed by 2995

Abstract

Acute lung injury/acute respiratory distress syndrome (ALI/ARDS), triggered by various pathogenic factors inside and outside the lungs, leads to diffuse lung injury and can result in respiratory failure and death, which are typical clinical critical emergencies. Severe acute pancreatitis (SAP), which has a poor clinical prognosis, is one of the most common diseases that induces ARDS. When SAP causes the body to produce a storm of inflammatory factors and even causes sepsis, clinicians will face a two-way choice between anti-inflammatory and anti-infection objectives while considering the damaged intestinal barrier and respiratory failure, which undoubtedly increases the difficulty of the diagnosis and treatment of SAP-ALI/ARDS. For a long time, many studies have been devoted to applying glucocorticoids (GCs) to control the inflammatory response and prevent and treat sepsis and ALI/ARDS. However, the specific mechanism is not precise, the clinical efficacy is uneven, and the corresponding side effects are endless. This review discusses the mechanism of action, current clinical application status, effectiveness assessment, and side effects of GCs in the treatment of ALI/ARDS (especially the subtype caused by SAP). Full article

(This article belongs to the Special Issue Intensive Care: Fundamental Aspects of Molecular Pathophysiology)

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