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International Journal of Molecular... Dec 2023Pre-eclampsia (PE) continues to be a leading cause of maternal and fetal mortality and morbidity. While substantial progress has been made in understanding the... (Review)
Review
Pre-eclampsia (PE) continues to be a leading cause of maternal and fetal mortality and morbidity. While substantial progress has been made in understanding the pathomechanisms of PE, the pathophysiology of the disease is still not fully understood. While the "two-stage model" of the development of PE is the most widely accepted theory, stating that the placenta is the main source of the disease, there are some other pathophysiological models of PE. Among these other theories, the one considering heart dysfunction as serving as the primary cause of PE seems to be gaining increasing prominence. In this review, we aim to elucidate these two divergent concepts concerning the development of PE. Despite some differences in their proposed pathomechanisms, both theories share vital pathophysiological elements in common. A central and critical component in both models is impaired placental perfusion, which appears to be a crucial phenomenon in PE. A comprehensive understanding of the different pathomechanisms involved in PE may be helpful in clinical practice, prompting a more individual approach to care of patients with PE.
Topics: Female; Pregnancy; Humans; Placenta; Pre-Eclampsia; Family; Pelvis; Perfusion
PubMed: 38203478
DOI: 10.3390/ijms25010307 -
The British Journal of Surgery Aug 2023Anastomotic leak is one of the most feared complications of colorectal surgery, and probably linked to poor blood supply to the anastomotic site. Several technologies... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Anastomotic leak is one of the most feared complications of colorectal surgery, and probably linked to poor blood supply to the anastomotic site. Several technologies have been described for intraoperative assessment of bowel perfusion. This systematic review and meta-analysis aimed to evaluate the most frequently used bowel perfusion assessment modalities in elective colorectal procedures, and to assess their associated risk of anastomotic leak. Technologies included indocyanine green fluorescence angiography, diffuse reflectance spectroscopy, laser speckle contrast imaging, and hyperspectral imaging.
METHODS
The review was preregistered with PROSPERO (CRD42021297299). A comprehensive literature search was performed using Embase, MEDLINE, Cochrane Library, Scopus, and Web of Science. The final search was undertaken on 29 July 2022. Data were extracted by two reviewers and the MINORS criteria were applied to assess the risk of bias.
RESULTS
Some 66 eligible studies involving 11 560 participants were included. Indocyanine green fluorescence angiography was most used with 10 789 participants, followed by diffuse reflectance spectroscopy with 321, hyperspectral imaging with 265, and laser speckle contrast imaging with 185. In the meta-analysis, the total pooled effect of an intervention on anastomotic leak was 0.05 (95 per cent c.i. 0.04 to 0.07) in comparison with 0.10 (0.08 to 0.12) without. Use of indocyanine green fluorescence angiography, hyperspectral imaging, or laser speckle contrast imaging was associated with a significant reduction in anastomotic leak.
CONCLUSION
Bowel perfusion assessment reduced the incidence of anastomotic leak, with intraoperative indocyanine green fluorescence angiography, hyperspectral imaging, and laser speckle contrast imaging all demonstrating comparable results.
Topics: Humans; Anastomotic Leak; Indocyanine Green; Anastomosis, Surgical; Digestive System Surgical Procedures; Perfusion
PubMed: 37253021
DOI: 10.1093/bjs/znad154 -
Bioscience Reports Aug 2023Salidroside (SAL), a phenolic natural product present in Rhodiola rosea, are commonly used in the treatment of various ischemic-hypoxic diseases, including intestinal...
ETHNOPHARMACOLOGICAL RELEVANCE
Salidroside (SAL), a phenolic natural product present in Rhodiola rosea, are commonly used in the treatment of various ischemic-hypoxic diseases, including intestinal ischemia-reperfusion (IR) injury. However, their efficacy and potential mechanisms in the treatment of intestinal IR injury have not been investigated.
OBJECTIVE
The objective of the present study is to investigate the pharmacological mechanism of action of SAL on intestinal IR injury using a network pharmacology approach combined with experimental validation.
METHODS
In the present study, we used the Traditional Chinese Medicine Systematic Pharmacology (TCMSP) database and analysis platform and Comparative Toxicogenomics Database (CTD) to predict possible target genes of SAL, collected relevant target genes of intestinal IR injury from GeneCards and DisGenet websites, and collected summary data to screen common target genes. Then, the protein-protein interaction (PPI) target network was constructed and analyzed by STRING database and Cytoscape 3.8.2 with the above intersecting genes. Then, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed and the component-target-pathway network was constructed, followed by the use of molecular docking and molecular dynamic simulation to verify the possible binding conformation between SAL and candidate targets to further explore the potential targets of SAL in the treatment of intestinal IR injury. Finally, an in vivo model of mouse superior mesenteric artery ligation was established to assess the anti-intestinal IR injury effect of SAL by assessing histopathological changes in mouse small intestine by HE staining, detecting inflammatory factor expression by ELISA kit, and detecting the expression of key protein targets by Western blotting.
RESULTS
A total of 166 SAL target genes and 1740 disease-related targets were retrieved, and 88 overlapping proteins were obtained as potential therapeutic targets. The pathway enrichment analysis revealed that the pharmacological effects of SAL on intestinal IR injury were anti-hypoxic, anti-inflammatory and metabolic pathway related, and the molecular docking and molecular dynamic simulation results showed that the core bioactive components had good binding affinity for TXNIP and AMPK, and the immunoblotting results indicated that the expression levels of TXNIP and AMPK in the small intestinal tissues of mice in the drug-treated group compared with the model group were significantly changed.
CONCLUSION
SAL may target AMPK and TXNIP domains to act as a therapeutic agent for intestinal IR. These findings comprehensively reveal the potential therapeutic targets for SAL against intestinal IR and provide theoretical basis for the clinical application of SAL in the treatment of intestinal IR.
Topics: Animals; Mice; Network Pharmacology; AMP-Activated Protein Kinases; Molecular Docking Simulation; Reperfusion; Reperfusion Injury; Drugs, Chinese Herbal
PubMed: 37530723
DOI: 10.1042/BSR20230539 -
International Journal of Molecular... Jul 2023Cerebral hypoperfusion is associated with enhanced cognitive decline and increased risk of neuropsychiatric disorders. Erythropoietin (EPO) is a neurotrophic factor...
Cerebral hypoperfusion is associated with enhanced cognitive decline and increased risk of neuropsychiatric disorders. Erythropoietin (EPO) is a neurotrophic factor known to improve cognitive function in preclinical and clinical studies of neurodegenerative and psychiatric disorders. However, the clinical application of EPO is limited due to its erythropoietic activity that can adversely elevate hematocrit in non-anemic populations. Carbamoylated erythropoietin (CEPO), a chemically engineered non-erythropoietic derivative of EPO, does not alter hematocrit and maintains neurotrophic and behavioral effects comparable to EPO. Our study aimed to investigate the role of CEPO in cerebral hemodynamics. Magnetic resonance imaging (MRI) analysis indicated increased blood perfusion in the hippocampal and striatal region without altering tight junction integrity. In vitro and in vivo analyses indicated that hippocampal neurotransmission was unaltered and increased cerebral perfusion was likely due to EDRF, CGRP, and NOS-mediated vasodilation. In vitro analysis using human umbilical vein endothelial cells (HUVEC) and hippocampal vascular gene expression analysis showed CEPO to be a non-angiogenic agent which regulates the MEOX2 gene expression. The results from our study demonstrate a novel role of CEPO in modulating cerebral vasodilation and blood perfusion.
Topics: Humans; Endothelial Cells; Erythropoietin; Epoetin Alfa; Gene Expression Regulation; Perfusion
PubMed: 37511274
DOI: 10.3390/ijms241411507 -
CNS Neuroscience & Therapeutics Feb 2024In the field of stroke thrombectomy, ineffective clinical and angiographic reperfusion after successful recanalization has drawn attention. Partial or complete... (Review)
Review
In the field of stroke thrombectomy, ineffective clinical and angiographic reperfusion after successful recanalization has drawn attention. Partial or complete microcirculatory reperfusion failure after the achievement of full patency of a former obstructed large vessel, known as the "no-reflow phenomenon" or "microvascular obstruction," was first reported in the 1960s and was later detected in both experimental models and patients with stroke. The no-reflow phenomenon (NRP) was reported to result from intraluminal occlusions formed by blood components and extraluminal constriction exerted by the surrounding structures of the vessel wall. More recently, an emerging number of clinical studies have estimated the prevalence of the NRP in stroke patients following reperfusion therapy, ranging from 3.3% to 63% depending on its evaluation methods or study population. Studies also demonstrated its detrimental effects on infarction progress and neurological outcomes. In this review, we discuss the research advances, underlying pathogenesis, diagnostic techniques, and management approaches concerning the no-reflow phenomenon in the stroke population to provide a comprehensive understanding of this phenomenon and offer references for future investigations.
Topics: Humans; No-Reflow Phenomenon; Microcirculation; Stroke; Thrombectomy; Reperfusion; Treatment Outcome
PubMed: 38358074
DOI: 10.1111/cns.14631 -
European Archives of... Jul 2023Arterial hypertension (AHTN), type 2 diabetes mellitus (DM), and atherosclerotic vascular disease (ASVD) are common vascular comorbidities in patients undergoing...
PURPOSE
Arterial hypertension (AHTN), type 2 diabetes mellitus (DM), and atherosclerotic vascular disease (ASVD) are common vascular comorbidities in patients undergoing reconstruction of the head and neck region with a microvascular free flap. These conditions may affect flap perfusion (microvascular blood flow and tissue oxygenation), which is a prerequisite for flap survival and thus reconstruction success. This study aimed to investigate the impacts of AHTN, DM, and ASVD on flap perfusion.
METHODS
Data from 308 patients who underwent successful reconstruction of the head and neck region with radial free forearm flaps, anterolateral thigh flaps, or fibula free flaps between 2011 and 2020 were retrospectively analyzed. Flap perfusion was measured intraoperatively and postoperatively with the O2C tissue oxygen analysis system. Flap blood flow, hemoglobin concentration, and hemoglobin oxygen saturation were compared between patients with and without AHTN, DM, and ASVD.
RESULTS
Intraoperative hemoglobin oxygen saturation and postoperative blood flow were lower in patients with ASVD than in patients without ASVD (63.3% vs. 69.5%, p = 0.046; 67.5 arbitrary units [AU] vs. 85.0 AU, p = 0.036; respectively). These differences did not persist in the multivariable analysis (all p > 0.05). No difference was found in intraoperative or postoperative blood flow or hemoglobin oxygen saturation between patients with and without AHTN or DM (all p > 0.05).
CONCLUSION
Perfusion of microvascular free flaps used for head and neck reconstruction is not impaired in patients with AHTN, DM, or ASVD. Unrestricted flap perfusion may contribute to the observed successful use of microvascular free flaps in patients with these comorbidities.
Topics: Humans; Free Tissue Flaps; Plastic Surgery Procedures; Retrospective Studies; Diabetes Mellitus, Type 2; Head and Neck Neoplasms; Perfusion; Hemoglobins
PubMed: 36897365
DOI: 10.1007/s00405-023-07913-1 -
Scientific Reports Aug 2023Cerebral blood flow differs between migraine patients and healthy controls during attack and the interictal period. This study compares the brain perfusion of episodic... (Clinical Trial)
Clinical Trial
Cerebral blood flow differs between migraine patients and healthy controls during attack and the interictal period. This study compares the brain perfusion of episodic migraine patients and healthy controls and investigates the influence of anodal transcranial direct current stimulation (tDCS) over the occipital cortex. We included healthy adult controls and episodic migraineurs. After a 28-day baseline period and the baseline visit, migraine patients received daily active or sham anodal tDCS over the occipital lobe for 28 days. All participants underwent a MRI scan at baseline; migraineurs were also scanned shortly after the stimulation period and about five months later. At baseline, brain perfusion of migraine patients and controls differed in several areas; among the stimulated areas, perfusion was increased in the cuneus of healthy controls. At the first visit, the active tDCS group had an increased blood flow in regions processing visual stimuli and a decreased perfusion in other areas. Perfusion did not differ at the second follow-up visit. The lower perfusion level in migraineurs in the cuneus indicates a lower preactivation level. Anodal tDCS over the occipital cortex increases perfusion of several areas shortly after the stimulation period, but not 5 months later. An increase in the cortical preactivation level could mediate the transient reduction of the migraine frequency.Trial registration: NCT03237754 (registered at clincicaltrials.gov; full date of first trial registration: 03/08/2017).
Topics: Adult; Humans; Brain; Cerebrovascular Circulation; Migraine Disorders; Perfusion; Transcranial Direct Current Stimulation
PubMed: 37626074
DOI: 10.1038/s41598-023-39659-5 -
Journal of Cardiothoracic Surgery Nov 2023In open thoracoabdominal aortic aneurysm (TAAA) repair, we have been performing vascular reconstruction under moderate to deep hypothermia and assisted circulation using...
BACKGROUND
In open thoracoabdominal aortic aneurysm (TAAA) repair, we have been performing vascular reconstruction under moderate to deep hypothermia and assisted circulation using simultaneous upper and lower body perfusion. This method is effective for protecting the spinal cord and the brain, heart, and abdominal organs and for avoiding lung damage.
METHODS
TAAA repair was performed under hypothermia at 20-28 °C in 18 cases (Crawford type I in 0 cases, type II in 5, type III in 3, type IV in 4, and Safi V in 6) between October 2014 and January 2023. Cardiopulmonary bypass was conducted by combined upper and lower body perfusion, with perfusion both via the femoral artery and either transapically or via the descending aorta or the left brachial artery.
RESULTS
The ischemic time for the artery of Adamkiewicz and the main segmental arteries was 40-124 min (75 ± 33 min). No spinal cord ischemic injury or brain or heart complications occurred. One patient with postoperative right renal artery occlusion and one with an infected aneurysm required tracheostomy, but the intubation time for the other 16 was 32 ± 33 h. The duration of postoperative intensive care unit stay was 6.5 ± 6.2 days, the length of hospital stay was 29 ± 15 days, and no in-hospital deaths occurred.
CONCLUSIONS
Simultaneous upper and lower body perfusion under moderate to deep hypothermia during thoracoabdominal aortic surgery may avoid not only spinal cord injury, but also cardiac and brain complications.
Topics: Humans; Aortic Aneurysm, Thoracic; Hypothermia; Treatment Outcome; Retrospective Studies; Spinal Cord Injuries; Perfusion; Aortic Aneurysm, Abdominal
PubMed: 37964285
DOI: 10.1186/s13019-023-02439-3 -
Transplantation Mar 2024Dynamic preservation methods such as normothermic, subnormothermic, and hypothermic machine perfusion circuits have emerged as viable alternatives to conventional static... (Review)
Review
Dynamic preservation methods such as normothermic, subnormothermic, and hypothermic machine perfusion circuits have emerged as viable alternatives to conventional static cold storage. These organ perfusion technologies serve as preservation methods and enable organ assessment, reconditioning, and repair before transplantation. Gene therapy is a novel strategy with the potential to transform the field of graft optimization and treatment. Thereby specific pathways involved in the transplantation process can be targeted and modified. This review aims to provide an overview of gene delivery methods during ex vivo machine perfusion of kidney and liver grafts. Recent literature on state-of-the-art gene therapy approaches during ex situ organ preservation, especially with respect to ischemia-reperfusion injury, as well as acute and chronic graft rejection have been analyzed. Additionally, potential challenges that could affect further refinement of this therapeutic modality are outlined.
Topics: Perfusion; Kidney; Organ Preservation; Kidney Transplantation; Extracorporeal Circulation
PubMed: 37482634
DOI: 10.1097/TP.0000000000004738 -
Fertility and Sterility Dec 2023To describe the feasibility of hypothermic machine perfusion (HMP) in uterus transplantation (UT) to potentially improve the preservation of the uterus and enhance graft...
OBJECTIVE
To describe the feasibility of hypothermic machine perfusion (HMP) in uterus transplantation (UT) to potentially improve the preservation of the uterus and enhance graft preservation in the donation after brainstem death (DBD) context. Uterus transplantation is a new surgical approach to treating absolute uterine infertility; it can be performed after living donation or after DBD. In the DBD context, the uterus is typically the last organ removed after other vital organs, with the exception of the Baylor team, which removes the uterus first. This key aspect imposes an unavoidable mild temperature ischemia for >1 hour on the uterus during the removal of the vital abdominal and chest organs. In renal transplantation, the perfusion machine reduces the risk of delayed graft function; thus, we hypothesized that machine perfusion could result in a reduction of uterus graft dysfunction. The uterus graft dysfunction could be expressed by a low embryo implantation rate, pregnancy loss, or vascular pregnancy diseases such as preeclampsia or fetal growth restriction." To date, static cold storage of the uterus is the only standard method for preservation before transplantation. HMP is an emerging method that could potentially improve the preservation of the uterus to enhance graft preservation in the DBD context.
DESIGN
This video article shows all the technical details of using the HMP for uterine transplantation.
SETTING
University.
ANIMALS
Porcine model.
INTERVENTION
Porcine uterus was retrieved from a DBD domestic animal model and flushed with KPS MP (Bridge To Life Ltd in UK) at 4 °C. After vascular preparation on the back table, the uterus was perfused using KPS MP through a cannula in the aorta using the VitaSmart device (Bridge To Life Ltd in UK) for 18 hours. Then, the uterus was transplanted to the porcine recipient.
MAIN OUTCOME MEASURES
The macroscopic appearance of the uterus at the end of HMP and the assessment of the uterus vascularization after transplantation in the recipient compared with the native uterus.
RESULTS
This video shows the cannulation of the iliac vessels, cooling and removal of the uterus on a porcine model, uterus preservation using HMP during 18 hours, and then UT in a new recipient pig with the reperfusion of the transplanted uterus next to the native, intact uterus of the recipient. The macroscopic appearance of the uterus at the end of HMP appeared viable and was perfectly flushed. The assessment of the uterus vascularization after transplantation in the recipient was similar to that of the native uterus. To our knowledge, we describe here for the first time the UT procedure in DBD context on an animal model and the use of HMP for uterus preservation in UT programs; this could increase the number of uterine grafts available for a greater number of female recipients.
CONCLUSION
Hypothermic machine perfusion could allow the duration of cold ischemia to be prolonged without altering the uterine graft. Nevertheless, this assertion has to be validated in a human context.
Topics: Animals; Female; Cold Temperature; Organ Preservation; Perfusion; Swine; Uterus
PubMed: 37660880
DOI: 10.1016/j.fertnstert.2023.08.020