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      Local carbachol application induces oral microvascular recruitment and improves gastric tissue oxygenation during hemorrhagic shock in dogs

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          Abstract

          Introduction

          Hemorrhagic shock is characterized by derangements of the gastrointestinal microcirculation. Topical therapy with nitroglycerine or iloprost improves gastric tissue oxygenation but not regional perfusion, probably due to precapillary adrenergic innervation. Therefore, this study was designed to investigate the local effect of the parasympathomimetic carbachol alone and in combination with either nitroglycerine or iloprost on gastric and oral microcirculation during hemorrhagic shock.

          Methods

          In a cross-over design five female foxhounds were repeatedly randomized into six experimental groups. Carbachol, or carbachol in combination with either nitroglycerine or iloprost were applied topically to the oral and gastric mucosa. Saline, nitroglycerine, or iloprost application alone served as control groups. Then, a fixed-volume hemorrhage was induced by arterial blood withdrawal followed by blood retransfusion after 1h of shock. Gastric and oral microcirculation was determined using reflectance spectrophotometry and laser Doppler flowmetry. Oral microcirculation was visualized with videomicroscopy. Statistics: 2-way-ANOVA for repeated measurements and Bonferroni post-hoc analysis (mean ± SEM; p < 0.05).

          Results

          The induction of hemorrhage led to a decrease of gastric and oral tissue oxygenation, that was ameliorated by local carbachol and nitroglycerine application at the gastric mucosa. The sole use of local iloprost did not improve gastric tissue oxygenation but could be supplemented by local carbachol treatment. Adding carbachol to nitroglycerine did not further increase gastric tissue oxygenation. Gastric microvascular blood flow remained unchanged in all experimental groups. Oral microvascular blood flow, microvascular flow index and total vessel density decreased during shock. Local carbachol supply improved oral vessel density during shock and oral microvascular flow index in the late course of hemorrhage.

          Conclusion

          The specific effect of shifting the autonomous balance by local carbachol treatment on microcirculatory variables varies between parts of the gastrointestinal tract. Contrary to our expectations, the improvement of gastric tissue oxygenation by local carbachol or nitroglycerine application was not related to increased microvascular perfusion. When carbachol is used in combination with local vasodilators, the additional effect on gastric tissue oxygenation depends on the specific drug combination. Therefore, modulation of tissue oxygen consumption, mitochondrial function or alterations in regional blood flow distribution should be investigated.

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          Most cited references55

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          The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine.

          Despite its very potent vasodilating action in vivo, acetylcholine (ACh) does not always produce relaxation of isolated preparations of blood vessels in vitro. For example, in the helical strip of the rabbit descending thoracic aorta, the only reported response to ACh has been graded contractions, occurring at concentrations above 0.1 muM and mediated by muscarinic receptors. Recently, we observed that in a ring preparation from the rabbit thoracic aorta, ACh produced marked relaxation at concentrations lower than those required to produce contraction (confirming an earlier report by Jelliffe). In investigating this apparent discrepancy, we discovered that the loss of relaxation of ACh in the case of the strip was the result of unintentional rubbing of its intimal surface against foreign surfaces during its preparation. If care was taken to avoid rubbing of the intimal surface during preparation, the tissue, whether ring, transverse strip or helical strip, always exhibited relaxation to ACh, and the possibility was considered that rubbing of the intimal surface had removed endothelial cells. We demonstrate here that relaxation of isolated preparations of rabbit thoracic aorta and other blood vessels by ACh requires the presence of endothelial cells, and that ACh, acting on muscarinic receptors of these cells, stimulates release of a substance(s) that causes relaxation of the vascular smooth muscle. We propose that this may be one of the principal mechanisms for ACh-induced vasodilation in vivo. Preliminary reports on some aspects of the work have been reported elsewhere.
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            Hemorrhagic Shock

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              Second consensus on the assessment of sublingual microcirculation in critically ill patients: results from a task force of the European Society of Intensive Care Medicine

              Hand-held vital microscopes (HVMs) were introduced to observe sublingual microcirculatory alterations at the bedside in different shock states in critically ill patients. This consensus aims to provide clinicians with guidelines for practical use and interpretation of the sublingual microcirculation. Furthermore, it aims to promote the integration of routine application of HVM microcirculatory monitoring in conventional hemodynamic monitoring of systemic hemodynamic variables.
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                Author and article information

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                Journal
                Front Immunol
                Front Immunol
                Front. Immunol.
                Frontiers in Immunology
                Frontiers Media S.A.
                1664-3224
                19 March 2024
                2024
                : 15
                : 1369617
                Affiliations
                [1] Department of Anesthesiology, Duesseldorf University Hospital , Duesseldorf, Germany
                Author notes

                Edited by: Pietro Ghezzi, University of Urbino Carlo Bo, Italy

                Reviewed by: Ivana Kawikova, University of Hartford, United States

                Wolfgang Weihs, Medical University of Vienna, Austria

                Christoph Thiemermann, Queen Mary University of London, United Kingdom

                *Correspondence: Stefan Hof, Stefan.hof@ 123456med.uni-duesseldorf.de

                †These authors have contributed equally to this work and share last authorship

                ‡In partial fulfillment of the requirements of the MD thesis of LL and MM

                Article
                10.3389/fimmu.2024.1369617
                10985194
                38566995
                f2214187-a6db-4427-8406-ad7402a42185
                Copyright © 2024 Hof, Lingens, Michels, Marcus, Kuebart, Herminghaus, Bauer, Picker, Truse and Vollmer

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 12 January 2024
                : 04 March 2024
                Page count
                Figures: 5, Tables: 5, Equations: 0, References: 55, Pages: 17, Words: 10588
                Funding
                The author(s) declare that no financial support was received for the research, authorship, and/or publication of this article.
                Categories
                Immunology
                Original Research
                Custom metadata
                Inflammation

                Immunology
                tissue oxygenation,microcirculation,microvascular recruitment,hemorrhagic shock,carbachol,nitroglycerine,iloprost,local drug application

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