Hemodynamic Management During Veno-Arterial Extracorporeal Membrane Oxygenation in Patients with Cardiogenic Shock: A Review

Abstract Background The use of veno-arterial extracorporeal membrane oxygenation (V-A ECMO) for cardiorespiratory support is increasing. However, few criteria for hemodynamic management have been described yet in V-A ECMO patients. Method We performed a review of hemodynamic management during V-A ECMO in CS patient based the literature published. We discuss how to optimize hemodynamic management. Results Patients on V-A ECMO require special hemodynamic management. It is crucial to maintain an adequate tissue oxygen supply and demand balance. Hemodynamic optimization is essential to support LV decompression and improve end-organ function and should be initiated immediately after initiating V-A ECMO support, during which more positive fluid balance is associated with worse outcomes. Conclusion The hemodynamic management of CS patients with V-A ECMO are complex and involves various aspect. Clinicians who care for patients on VA ECMO should combined use many availability indicators to guide hemodynamic management

Decreased Heart Rate Variability in COVID-19

Abstract Purpose Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which primarily infects the lower airways and binds to angiotensin-converting enzyme 2 (ACE2) on alveolar epithelial cells. ACE2 is widely expressed not only in the lungs but also in the cardiovascular system. Therefore, SARS-CoV-2 can also damage the myocardium. This report aimed to highlight decreased heart rate variability (HRV) and cardiac injury caused by SARS-CoV-2. Materials and Methods We evaluated three COVID-19 patients who died. Patients’ data were collected from electronic medical records. We collected patient’s information, including baseline information, lab results, body temperature, heart rate (HR), clinical outcome and other related data. We calculated the HRV and the difference between the expected and actual heart rate changes as the body temperature increased. Results As of March 14, 2020, 3 (2.2%) of 136 patients with COVID-19 in Tianjin died in the early stage of the COVID-19 epidemic. The immediate cause of death for Case 1, Case 2, and Case 3 was cardiogenic shock, cardiac arrest and cardiac arrest, respectively. The HRV were substantially decreased in the whole course of all three cases. The actual increases in heart rate were 5 beats/min, 13 beats/min, and 4 beats/min, respectively, less than expected as their temperature increased. Troponin I and Creatine Kinase MB isoenzyme (CK-MB) were substantially increased only in Case 3, for whom the diagnosis of virus-related cardiac injury could not be made until day 7. In all three cases, decreased in HRV and HR changes occurred earlier than increases in cardiac biomarkers (e.g., troponin I and CK-MB). Conclusions In conclusion, COVID-19 could affect HRV and counteract tachycardia in response to increases in body temperature. The decreases of HRV and HR changes happened earlier than the increases of myocardial markers (troponin I and CK-MB). It suggested the decreases of HRV and HR changes might help predict cardiac injury earlier than myocardial markers in COVID-19, thus its early identification might help improve patient prognosis

Multicentre, parallel, open-label, two-arm, randomised controlled trial on the prognosis of electrical impedance tomography-guided versus low PEEP/FiO2 table-guided PEEP setting: a trial protocol

Introduction Previous studies suggested that electrical impedance tomography (EIT) has the potential to guide positive end-expiratory pressure (PEEP) titration via quantifying the alveolar collapse and overdistension. The aim of this trial is to compare the effect of EIT-guided PEEP and acute respiratory distress syndrome (ARDS) network low PEEP/fraction of inspired oxygen (FiO2) table strategy on mortality and other clinical outcomes in patients with ARDS.Methods This is a parallel, two-arm, multicentre, randomised, controlled trial, conducted in China. All patients with ARDS under mechanical ventilation admitted to the intensive care unit will be screened for eligibility. The enrolled patients are stratified by the aetiology (pulmonary/extrapulmonary) and partial pressure of arterial oxygen/FiO2 (≥150 mm Hg or <150 mm Hg) and randomised into the intervention group or the control group. The intervention group will receive recruitment manoeuvre and EIT-guided PEEP titration. The EIT-guided PEEP will be set for at least 12 hours after titration. The control group will not receive recruitment manoeuvre routinely and the PEEP will be set according to the lower PEEP/FiO2 table proposed by the ARDS Network. The primary outcome is 28-day survival.Analysis Qualitative data will be analysed using the χ2 test or Fisher’s exact test, quantitative data will be analysed using independent samples t-test or Mann-Whitney U test. Kaplan-Meier analysis with log-rank test will be used to evaluate the 28-day survival rate between two groups. All outcomes will be analysed based on the intention-to-treat principle.Ethics and dissemination The trial is approved by the Institutional Research and Ethics Committee of the Peking Union Medical College Hospital. Data will be published in peer-reviewed journals.Trial registration number NCT05307913

Protective Effects of N-Acetylcysteine in Concanavalin A-Induced Hepatitis in Mice

This study was designed to study the protective effects and mechanisms of N-acetylcysteine (NAC) in concanavalin A-induced hepatitis in mice. In this study, pretreatment with NAC ameliorated the histopathological changes and suppressed inflammatory cytokines in ConA-induced hepatitis. The expression of IL-2, IL-6, TNF-α, and IFN-γ was significantly reduced in the NAC-treated groups. NAC activated PI3K/Akt pathway and inhibited the activation of NF-κB. Additionally, NAC reduced autophagosome formation, as assessed by detecting the expression of LC3 and Beclin 1. Our results demonstrate that NAC can alleviate ConA-induced hepatitis by regulating the PI3K/Akt pathway and reducing the late stages of autophagy. Our results described a new pharmaceutical to provide more effective therapies for immune hepatitis

Nucleotide sequences of primers used for qRT-PCR.

<p>Nucleotide sequences of primers used for qRT-PCR.</p

Protective Effects of Astaxanthin on ConA-Induced Autoimmune Hepatitis by the JNK/p-JNK Pathway-Mediated Inhibition of Autophagy and Apoptosis

<div><p>Objective</p><p>Astaxanthin, a potent antioxidant, exhibits a wide range of biological activities, including antioxidant, atherosclerosis and antitumor activities. However, its effect on concanavalin A (ConA)-induced autoimmune hepatitis remains unclear. The aim of this study was to investigate the protective effects of astaxanthin on ConA-induced hepatitis in mice, and to elucidate the mechanisms of regulation.</p><p>Materials and Methods</p><p>Autoimmune hepatitis was induced in in Balb/C mice using ConA (25 mg/kg), and astaxanthin was orally administered daily at two doses (20 mg/kg and 40 mg/kg) for 14 days before ConA injection. Levels of serum liver enzymes and the histopathology of inflammatory cytokines and other maker proteins were determined at three time points (2, 8 and 24 h). Primary hepatocytes were pretreated with astaxanthin (80 μM) in vitro 24 h before stimulation with TNF-α (10 ng/ml). The apoptosis rate and related protein expression were determined 24 h after the administration of TNF-α.</p><p>Results</p><p>Astaxanthin attenuated serum liver enzymes and pathological damage by reducing the release of inflammatory factors. It performed anti-apoptotic effects via the descending phosphorylation of Bcl-2 through the down-regulation of the JNK/p-JNK pathway.</p><p>Conclusion</p><p>This research firstly expounded that astaxanthin reduced immune liver injury in ConA-induced autoimmune hepatitis. The mode of action appears to be downregulation of JNK/p-JNK-mediated apoptosis and autophagy.</p></div

Effects of olive oil and astaxanthin on the liver function and pathology of healthy mice.

<p>(A) The levels of serum ALT and AST in the four groups did not differ. Data are given as means ± SD (n = 6, P > 0.05). (B) The percentage of different immune cell subsets, serum levels of TNF-α, IL-6, IL-1β, and IFN-γ of four groups were evaluated in each group with ELISAs or flow cytometry (n = 6, P > 0.05). (C) Representative hematoxylin-and-eosin-stained sections of the liver. Original magnification, ×200.</p

Effects of astaxanthin on the regulation of the TNF-α/JNK/p-JNK pathway in mice with ConA-induced acute hepatitis.

<p>(A) The expression of TNF-α and TRAF2 was determined with real-time PCR (n = 8, *P < 0.05 for Oil versus ConA, ^#P < 0.05 for ConA+Astaxanthin (20) versus ConA, ⁺P < 0.05 for ConA+Astaxanthin (40) versus ConA). (B) The levels of proteins TNF-α, TRAF2, JNK, and p-JNK in liver tissue are shown as western blot bands. (C) The expression of TNF-α and p-JNK in hepatic tissues was determined with immunohistochemistry at 8 h (original magnification, 200) and their IODs changed significantly with astaxanthin treatment (n = 8, *P < 0.05 for ConA+Astaxanthin (20) versus ConA, ^#P < 0.05 for ConA+Astaxanthin (40) versus ConA). (D) The levels of proteins ERK, p-ERK, P38 MAPK, and p-P38 MAPK in liver tissue are shown as western blot bands. The relative band densities were calculated (n = 3, *P < 0.05 for Oil versus ConA, ^#P < 0.05 for ConA+Astaxanthin (20) versus ConA, ⁺P < 0.05 for ConA+Astaxanthin (40) versus ConA).</p

Effects of astaxanthin on the production of NF-κB p65, IL-6, IL-1β, and IFN-γ in mice with ConA-induced acute hepatitis.

<p>(A) The index of plasma TNF-α, IL-6, IL-1β, and IFN-γ, measured with ELISAs, was reduced by astaxanthin pretreatment in mice at doses of both 20 mg/kg and 40 mg/kg. Data are presented as means ± SD (n = 8, *P < 0.05 for Oil versus ConA, ^#P < 0.05 for ConA+Astaxanthin (20) versus ConA, ⁺P < 0.05 for ConA+Astaxanthin (40) versus ConA). (B) The mRNA levels of NF-κB p65, IL-6, IL-1β, and IFN-γ were evaluated in each group with real-time PCR (n = 8, *P < 0.05 for Oil versus ConA, ^#P < 0.05 for ConA+Astaxanthin (20) versus ConA, ⁺P < 0.05 for ConA+Astaxanthin (40) versus ConA). (C) The expression levels of the NF-κB p65, IL-6, IL-1β, and IFN-γ proteins were determined with western blotting.</p