Immune cell expression patterns of CD39/CD73 ectonucleotidases in rodent models of cardiac arrest and resuscitation

BackgroundCardiac arrest (CA) is a significant public health concern. There is the high imminent mortality and survival in those who are resuscitated is substantively compromised by the post-CA syndrome (PCAS), characterized by multiorgan ischemia–reperfusion injury (IRI). The inflammatory response in PCAS is complex and involves various immune cell types, including lymphocytes and myeloid cells that have been shown to exacerbate organ IRI, such as myocardial infarction. Purinergic signaling, as regulated by CD39 and CD73, has emerged as centrally important in the context of organ-specific IRI. Hence, comprehensive understanding of such purinergic responses may be likewise imperative for improving outcomes in PCAS.MethodsWe have investigated alterations of immune cell populations after CA by utilizing rodent models of PCAS. Blood and spleen were collected after CA and resuscitation and underwent flow cytometry analysis to evaluate shifts in CD3+CD4+ helper T cells, CD3+CD8a+ cytotoxic T cells, and CD4/CD8a ratios. We then examined the expression of CD39 and CD73 across diverse cell types, including myeloid cells, T lymphocytes, and B lymphocytes.ResultsIn both rat and mouse models, there were significant increases in the frequency of CD3+CD4+ T lymphocytes in PCAS (rat, P < 0.01; mouse, P < 0.001), with consequently elevated CD4/CD8a ratios in whole blood (both, P < 0.001). Moreover, CD39 and CD73 expression on blood leukocytes were markedly increased (rat, P < 0.05; mouse, P < 0.01 at 24h). Further analysis in the experimental mouse model revealed that CD11b+ myeloid cells, with significant increase in their population (P < 0.01), had high level of CD39 (88.80 ± 2.05 %) and increased expression of CD73 (P < 0.05). CD19+ B lymphocytes showed slight increases of CD39 (P < 0.05 at 2h) and CD73 (P < 0.05 at 2h), while, CD3+ T lymphocytes had decreased levels of them. These findings suggested a distinct patterns of expression of CD39 and CD73 in these specific immune cell populations after CA.ConclusionsThese data have provided comprehensive insights into the immune response after CA, highlighting high-level expressions of CD39 and CD73 in myeloid cells

Association of tissue oxygen saturation levels with skeletal muscle injury in the critically ill

This study aimed to investigate the association between the level of tissue oxygen saturation (StO2) and quadriceps/skeletal muscle dysfunction, measured using the Medical Research Council (MRC) scale and ultrasonography, in critically ill patients. Thirty-four patients hospitalized at the Critical Care Medicine Center of Kindai University Hospital, between January 2022 and March 2023, were enrolled in this study. The StO2 of the quadriceps muscle was measured via near-infrared spectroscopy. Muscle atrophy was measured by the thickness, cross-sectional area (CSA), and echo intensity of the rectus femoris (RF). These values were evaluated every alternate day until 13 days after admission or until discharge, whichever occurred first. Muscle weakness was assessed using the sum score of the MRC scale (MRC-SS), with the patient sitting at bedside. The mean age of the patients was 67.3 ± 15.3 years, and 20 (59%) were men. Seven patients (21%) were admitted for trauma, and 27 (79%) were admitted for medical emergencies or others. The mean score for the MRC-SS was 51.0 ± 7.9 points. RF thickness and CSA significantly decreased after day 7 (p &lt; 0.05). There were no significant changes in StO2 levels during hospitalization. However, there were positive correlations between the nadir StO2 during hospitalization and MRC-SS, and changes in RF thickness and CSA at discharge (r = 0.41, p = 0.03; r = 0.37, p = 0.03; and r = 0.35, p = 0.05, respectively). StO2 in the quadriceps muscle may be useful for predicting muscle atrophy and dysfunction in patients with critical illnesses.</p

S-100B and neuron-specific enolase as predictors of neurological outcome in patients after cardiac arrest and return of spontaneous circulation: a systematic review

INTRODUCTION: Neurological prognostic factors after cardiopulmonary resuscitation (CPR) in patients with cardiac arrest (CA) as early and accurately as possible are urgently needed to determine therapeutic strategies after successful CPR. In particular, serum levels of protein neuron-specific enolase (NSE) and S-100B are considered promising candidates for neurological predictors, and many investigations on the clinical usefulness of these markers have been published. However, the design adopted varied from study to study, making a systematic literature review extremely difficult. The present review focuses on the following three respects for the study design: definitions of outcome, value of specificity and time points of blood sampling. METHODS: A Medline search of literature published before August 2008 was performed using the following search terms: "NSE vs CA or CPR", "S100 vs CA or CPR". Publications examining the clinical usefulness of NSE or S-100B as a prognostic predictor in two outcome groups were reviewed. All publications met with inclusion criteria were classified into three groups with respect to the definitions of outcome; "dead or alive", "regained consciousness or remained comatose", and "return to independent daily life or not". The significance of differences between two outcome groups, cutoff values and predictive accuracy on each time points of blood sampling were investigated. RESULTS: A total of 54 papers were retrieved by the initial text search, and 24 were finally selected. In the three classified groups, most of the studies showed the significance of differences and concluded these biomarkers were useful for neurological predictor. However, in view of blood sampling points, the significance was not always detected. Nevertheless, only five studies involved uniform application of a blood sampling schedule with sampling intervals specified based on a set starting point. Specificity was not always set to 100%, therefore it is difficult to indiscriminately assess the cut-off values and its predictive accuracy of these biomarkers in this meta analysis. CONCLUSIONS: In such circumstances, the findings of the present study should aid future investigators in examining the clinical usefulness of these markers and determination of cut-off values

Erosion and Sedimentation During the September 2015 Flooding of the Kinu River, Central Japan

Erosional and sedimentary features associated with flooding have been documented in both modern and past cases. However, only a few studies have demonstrated the relationship between these features and the corresponding hydraulic conditions that produced them, making it difficult to evaluate the magnitude of paleo-flooding. This study describes the characteristics associated with inundation depth and flow direction, as well as the erosional and sedimentary features resulting from the disastrous flooding of the Kinu River, central Japan, in September 2015. Water levels rose rapidly due to heavy rainfall that eventually overtopped, and subsequently breached, a levee in Joso City, causing destructive flooding on the surrounding floodplain. Distinctive erosional features are found next to the breached levee, while depositional features, such as a sandy crevasse-splay deposit are found further away from the breach. The deposit can be divided into three units based on sedimentary facies. The vertical and lateral changes of these sedimentary facies may be the result of temporal and spatial changes associated with flow during the single flooding event. These observations and quantitative data provide information that can be used to reveal the paleohydrology of flood deposits in the stratigraphic record, leading to improved mitigation of future flooding disasters

The Responses of Tissues from the Brain, Heart, Kidney, and Liver to Resuscitation following Prolonged Cardiac Arrest by Examining Mitochondrial Respiration in Rats

Cardiac arrest induces whole-body ischemia, which causes damage to multiple organs. Understanding how each organ responds to ischemia/reperfusion is important to develop better resuscitation strategies. Because direct measurement of organ function is not practicable in most animal models, we attempt to use mitochondrial respiration to test efficacy of resuscitation on the brain, heart, kidney, and liver following prolonged cardiac arrest. Male Sprague-Dawley rats are subjected to asphyxia-induced cardiac arrest for 30 min or 45 min, or 30 min cardiac arrest followed by 60 min cardiopulmonary bypass resuscitation. Mitochondria are isolated from brain, heart, kidney, and liver tissues and examined for respiration activity. Following cardiac arrest, a time-dependent decrease in state-3 respiration is observed in mitochondria from all four tissues. Following 60 min resuscitation, the respiration activity of brain mitochondria varies greatly in different animals. The activity after resuscitation remains the same in heart mitochondria and significantly increases in kidney and liver mitochondria. The result shows that inhibition of state-3 respiration is a good marker to evaluate the efficacy of resuscitation for each organ. The resulting state-3 respiration of brain and heart mitochondria following resuscitation reenforces the need for developing better strategies to resuscitate these critical organs following prolonged cardiac arrest

第665回 千葉医学会例会・第18回 佐藤外科例会 44.

Additional manuscript. The contents include methods and results of "Estimated Blood Levels of IL-6 during CVVH Operation", "Blood Gas Analysis", "Table E1. Basal characteristics and resuscitation data of randomized animals" and "Table E2. Efficacy of hemofilter on IL-6 removal from circulating blood". (DOCX 305 kb

Developing dual hemofiltration plus cardiopulmonary bypass in rodents

Background: Emerging therapies for prolonged cardiac arrest (CA) include advanced circulatory interventions like emergency cardiopulmonary bypass (ECPB) and continuous venovenous hemofiltration (CVVHF). However, preclinical studies are limited because of the absence of a practical method of using CVVHF along with ECPB in rodents. ;Methods: We modified a CA model with ECPB resuscitation to include the CVVHF circuit. Adult rats were cannulated via the femoral artery or vein and the jugular vein for the ECPB circuit. A new circuit for CVVHF was added to allow ECPB and CVVHF to be started simultaneously. CVVHF blood flow at 3 mL/min could be controlled with a screw clamp during ECPB. After cessation of ECPB, the CVVHF flow was maintained using a roller pump. The filtration rate was controlled at 40 mL/h/kg in the standard volume of CVVHF and 120 mL/h/kg in the high volume (HV) of CVVHF. The driving force of hemofiltration was evaluated by monitoring transmembrane pressure and filter clearance (FCL). ;Results: Transmembrane pressure in both groups was stable for 6 h throughout CVVHF. FCL of blood urea nitrogen and potassium in the standard volume group was significantly less than the HV group (P &lt; 0.01). FCL of blood urea nitrogen and potassium was stable throughout the CVVHF operation in both groups. ;Conclusions: We developed a method of CVVHF along with ECPB in rodents after CA. We further demonstrated the ability to regulate both standard and HV filtration rates. (C) 2015 Elsevier Inc. All rights reserved