treatment of myocardial dysfunction in sepsis

Sepsis-induced myocardial dysfunction (SIMD) is a prevalent and severe form of organ dysfunction with elusive underlying mechanisms and limited treatment options. In this study, the cecal ligation and puncture and lipopolysaccharide (LPS) were used to reproduce sepsis model in vitro and vivo. The level of voltage-dependent anion channel 2 (VDAC2) malonylation and myocardial malonyl-CoA were detected by mass spectrometry and LC-MS-based metabolomics. Role of VDAC2 malonylation on cardiomyocytes ferroptosis and treatment effect of mitochondrial targeting nano material TPP-AAV were observed...

BACKGROUND: Myocardial injury is a serious consequence of sepsis that contributes to high rates of death. Currently, the pathophysiology of cardiac damage in sepsis is still unknown, and treatment approaches are limited. METHODS: The sepsis mouse model was established inducing by Lipopolysaccharide (LPS) in vivo and Tectorigenin was pretreated to explore whether it contributed to alleviated myocardial injury. Hematoxylin-eosin (HE) stain was employed to evaluate the myocardial injury severity...

INTRODUCTION: In lieu of limited studies on the timing of burn wound eschar excision for burns, a more comprehensive analysis is indicated to determine the effects of early wound excision following burns. This study aims to address the outcomes of early wound excision in burn patients. METHODS: Data collection were from TriNetX research database. Three groups of burn patients were stratified by the number of days in which they received burn wound excision within 14 days of injury...

Objective: Endotoxemic cardiac dysfunction contributes to greater morbidity and mortality in elderly patients with sepsis. This study tested the hypothesis that Klotho insufficiency in aging heart exaggerates and prolongs myocardial inflammation to hinder cardiac function recovery following endotoxemia. Methods: Endotoxin (0.5 mg/kg, iv) was administered to young adult (3-4 months) and old (18-22 months) mice with or without subsequent treatment with recombinant interleukin-37 (IL-37, 50 µg/kg, iv) or recombinant Klotho (10 µg/kg, iv)...

Myocardial edema mediated by endothelial dysfunction plays an important role in sepsis-induced cardiomyopathy (SIC); however, its mechanism is unclear. The current study aimed to provide evidence on the cardioprotection of CD1d-dependent natural killer T (NKT) cells and clarify the possible mechanism in a mouse model of sepsis. Wild-type (WT) and CD1d-dependent NKT-cells inactivation (CD1dko) mice were subjected to sepsis induced by intraperitoneal injection of lipopolysaccharide (LPS). The NKT-cells number and CD1d expression were both increased in the hearts and blood of WT mice after LPS treatment...

BACKGROUND: To identify differentially expressed lipid metabolism-related genes (DE-LMRGs) responsible for immune dysfunction in sepsis. METHODS: The lipid metabolism-related hub genes were screened using machine learning algorithms, and the immune cell infiltration of these hub genes were assessed by CIBERSORT and Single-sample GSEA. Next, the immune function of these hub genes at the single-cell level were validated by comparing multiregional immune landscapes between septic patients (SP) and healthy control (HC)...

BACKGROUND: Large-dose melatonin treatment in animal experiments was hardly translated into humans, which may explain the dilemma that the protective effects against myocardial injury in animal have been challenged by clinical trials. Ultrasound-targeted microbubble destruction (UTMD) has been considered a promising drug and gene delivery system to the target tissue. We aim to investigate whether cardiac gene delivery of melatonin receptor mediated by UTMD technology optimizes the efficacy of clinically equivalent dose of melatonin in sepsis-induced cardiomyopathy...

AIMS: Lipopolysaccharide (LPS) is a well-known agent to induce septic conditions. Sepsis-induced cardiomyopathy has an overwhelming death rate. Carvacrol (CVL), a monoterpene phenol, has anti-inflammatory and antioxidant properties. The research aimed to investigate the effect of CVL on LPS-induced dysfunction in the heart. In this study, we evaluated the effect of CVL in LPS-stimulated H9c2 cardiomyoblast cells and Balb/c mice. MAIN METHODS: LPS was used to induce septic conditions in H9c2 cardiomyoblast cells in vitro and in Balb/C mice...

BACKGROUND: Despite advances in the treatment of sepsis over time, this condition remains both a serious threat and a cause of death among critical patients. OBJECTIVE: This study aimed to explore the role of the nuclear factor kappa B (NF-κB) signaling pathway in the development of septic cardiomyopathy in rats with sepsis. METHOD: A total of 32 Sprague Dawley rats were randomized into a sham operation group and three groups with sepsis, which were tested at one of the following time-points: 3, 6, or 12 h...

Sepsis-induced myocardial dysfunction is the main reason for mortality and morbidity. Recent investigations have shown that inflammation and oxidative stress play a central role in lipopolysaccharide (LPS)-induced cardiac injury pathophysiology. Gum-resin extracts of Boswellia serrata have been traditionally used in folk medicine for centuries to treat various chronic inflammatory diseases. The present study aimed to investigate the effects of B. serrata pretreatment on LPS-induced cardiac damage in H9c2 cells...

BACKGROUND: Thrombotic microangiopathy (TMA) syndromes include thrombotic thrombocytopenic purpura (TTP) and haemolytic uremic syndrome, and contribute to myocardial infarction and multiple organ failure. Although coronary microvascular dysfunction (CMD) is the key for understanding the pathophysiology of cardiac involvement in TMA, there is limited knowledge on the recovery from CMD in patients with TMA. CASE SUMMARY: An 80-year-old woman was brought to the emergency department due to worsening back pain, dyspnoea on exertion, jaundice, and fever...

Myocardial cell damage is associated with apoptosis and excessive inflammatory response in sepsis. Histone deacetylases (HDACs) are implicated in the progression of heart diseases. This study aims to explore the role of histone deacetylase 9 (HDAC9) in sepsis-induced myocardial injury. Lipopolysaccharide (LPS)-induced Sprague Dawley rats and cardiomyocyte line H9C2 were used as models in vivo and in vitro. The results showed that HDAC9 was significantly upregulated after LPS stimulation, and HDAC9 knockdown remarkably improved cardiac function, as evidenced by decreased LVEDD and LVESD, and increased FS% and EF%...

Sepsis is a systemic inflammatory response syndrome of suspected or documented infectious origin, whose outcome is multiorgan failure. Sepsis-induced myocardial dysfunction (SIMD), present in more than 50% of septic patients, is characterized by (i) left ventricular (LV) dilatation with normal or low filling pressure, (ii) right and/or LV (systolic and/or diastolic) dysfunction and (iii) reversibility. Since the first definition proposed by Parker et al. in 1984, attempts have been made to define SIMD. Many parameters are used to assess cardiac function in septic patients, sometimes making it more difficult to measure due to the intrinsic hemodynamical changes in this condition...

BACKGROUND: Previous studies have implicated p53-dependent mitochondrial dysfunction in sepsis induced end organ injury, including sepsis-induced myocardial dysfunction (SIMD). However, the mechanisms behind p53 localization to the mitochondria have not been well established. Dynamin-related protein 1 (Drp1), a mediator of mitochondrial fission, may play a role in p53 mitochondrial localization. Here we examined the role of Drp1/p53 interaction in SIMD using in vitro and murine models of sepsis...

BACKGROUND: Dexmedetomidine (DEX) administered before or at 30 min after sepsis induction was reported to alleviate septic cardiomyopathy in experimental models. However, sepsis is a life-threatening organ dysfunction due to infection-induced dysregulated host response, whether DEX treatment in the presence of organ dysfunction affects septic cardiomyopathy is unknown. This study investigated the effect of DEX posttreatment on septic cardiomyopathy. METHODS: Male wild-type and α2A -adrenergic receptor (AR) knockout mice were exposed to lipopolysaccharide (LPS) or cecal ligation puncture (CLP), and cultured cardiac endothelial cells were used...

Sepsis causes multiple organ injuries, among which the heart is one most severely damaged organ. Melatonin (MEL) alleviates septic myocardial injury, although a systematic and comprehensive approach is still lacking to understand the precise protective machinery of MEL. This study aimed to examine the underlying mechanisms of MEL on improvement of septic myocardial injury at a systematic level. This study integrated three analytic modalities including database investigations, RNA-seq analysis, and weighted gene co-expression network analysis (WCGNA), in order to acquire a set of genes associated with the pathogenesis of sepsis...

Cardiac dysfunction is a common complication in patients with sepsis triggering high morbidity and mortality. Lycorine (LYC), the main effective monomer component extracted from Lycoris bulbs, possesses antiviral, anti-inflammatory, analgesic, liver protection properties. In this study, the effect of LYC pre- and post-treatment as well as the underlying mechanism were evaluated in the cecal ligation and puncture (CLP) model of Balb/c mice. The survival rate, anal temperature, sepsis score, blood biochemical/routine indicators, cardiac function, sepsis-related pathophysiological processes, and AMPK signaling in septic mice were observed by echocardiography, histological staining, western blot, qPCR, and etc...

Myocardial dysfunction is an important complication of sepsis and an important cause of death in sepsis patients. Sepsis will significantly change the composition of gut microbiota, and the destruction of gut microbiota also creates conditions for the occurrence and progression of sepsis. Gut microbiota is an important player in myocardial injury in sepsis. This review elaborates on the possible mechanisms of gut microbiota affecting myocardial injury in sepsis, including short-chain fatty acids, trimethylamine and trimethylamine oxides, various cytokines, and mitochondrial dysfunction...

Background: Sepsis-induced cardiomyopathy (SIC) is a severe myocardial dysfunction secondary to septicemia. It is a major concern owing to the high mortality and morbidity, which are greatly influenced by ferroptosis. Resveratrol (RSV) is a naturally existing agonist of the silent information regulator 1 (Sirt1). It has cardioprotective effects against sepsis-induced myocardial injury, However, the detailed mechanism is unknown. Methods: In this study, cecal ligation and puncture (CLP)-induced septic rats were employed to assess the changes in ferroptosis with RSV administration...

Sepsis is a life-threatening syndrome with multi-organ dysfunction in critical care medicine. With the occurrence of sepsis-induced cardiomyopathy (SIC), characterized by reduced ventricular contractility, the mortality of sepsis is boosted to 70-90%. Pyruvate kinase M2 (PKM2) functions in a variety of biological processes and diseases other than glycolysis, and has been documented as a cardioprotective factor in several heart diseases. It is currently unknown whether PKM2 influences the development of SIC...