losartan-potassium and Respiratory-Distress-Syndrome

The novel coronavirus 2019-nCoV (SARS-CoV-2) infection that emerged in China in December 2019 has rapidly spread to become a global pandemic. This article summarizes the potential benefits of erythropoietin (EPO) in alleviating SARS-CoV-2 pathogenesis which is now called COVID-19. As with other coronavirus infection, the lethality of COVID-19 is associated with respiratory dysfunction due to overexpression of proinflammatory cytokines induced by the host immune responses. The resulting cytokine storm leads to the development of acute lung injury/acute respiratory distress syndrome (ALI/ARDS). Erythropoietin, well known for its role in the regulation of erythropoiesis, may have protective effects against ALI/ARDS induced by viral and other pathogens. EPO exerts antiapoptotic and cytoprotective properties under various pathological conditions. With a high safety profile, EPO promotes the production of endothelial progenitor cells and reduce inflammatory processes through inhibition of the nuclear factor-κB (NF-κB) and JAK-STAT3 signaling pathways. Thus, it may be considered as a safe drug candidate for COVID-19 patients if given at the early stage of the disease. The potential effects of erythropoietin on different aspects of ALI/ARDS associated with SARS-CoV-2 infection are reviewed.

Topics: Acute Lung Injury; Anti-Inflammatory Agents; COVID-19; COVID-19 Drug Treatment; Cytokine Release Syndrome; Erythropoietin; Humans; Respiratory Distress Syndrome; SARS-CoV-2

Current pharmacotherapy for acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) is not optimal, and the biological and physiological complexity of these severe lung injury syndromes requires consideration of combined-agent treatments or agents with pleiotropic action. In this regard, exogenous erythropoietin (EPO) represents a possible candidate since a number of preclinical studies have revealed beneficial effects of EPO administration in various experimental models of ALI. Taken together, this treatment strategy is not a single mediator approach, but it rather provides protection by modulating multiple levels of early signaling pathways involved in apoptosis, inflammation, and peroxidation, potentially restoring overall homeostasis. Furthermore, EPO appears to confer vascular protection by promoting angiogenesis. However, only preliminary studies exist and more experimental and clinical studies are necessary to clarify the efficacy and potentially cytoprotective mechanisms of EPO action. In addition to the attempts to optimize the dose and timing of EPO administration, it would be of great value to minimize any potential toxicity, which is essential for EPO to fulfill its role as a potential candidate for the treatment of ALI in routine clinical practice. The present article reviews recent advances that have elucidated biological and biochemical activities of EPO that may be potentially applicable for ALI/ARDS management.

Topics: Acute Lung Injury; Erythropoietin; Humans; Recombinant Proteins; Respiratory Distress Syndrome

The incidence of adult respiratory distress syndrome (ARDS) in severe traumatic brain injury (TBI) is poorly reported. Recently, a new definition for ARDS was proposed, the Berlin definition. The percentage of patients represented by TBI in the Berlin criteria study is limited. This study describes the incidence and associated mortality of ARDS in TBI patients.. The study was an analysis of the safety of erythropoietin administration and transfusion threshold on the incidence of ARDS in severe TBI patients. Three reviewers independently assessed all patients enrolled in the study for acute lung injury/ARDS using the Berlin and the American-European Consensus Conference (AECC) definitions. A Cox proportional hazards model was used to assess the relationship between ARDS and mortality and 6-month Glasgow Outcome Scale (GOS) score.. Two hundred patients were enrolled in the study. Of the patients, 21% (41 of 200) and 26% (52 of 200) developed ARDS using the AECC and Berlin definitions, respectively, with a median time of 3 days (interquartile range, 3) after injury. ARDS by either definition was associated with increased mortality (p = 0.04) but not with differences in functional outcome as measured by the GOS score at 6 months. Adjusted analysis using the Berlin criteria showed an increased mortality associated with ADS (p = 0.01).. Severe TBI is associated with an incidence of ARDS ranging from 20% to 25%. The incidence is comparable between the Berlin and AECC definitions. ARDS is associated with increased mortality in severe TBI patients, but further studies are needed to validate these findings.. Epidemiologic study, level II.

Topics: Adolescent; Adult; Blood Transfusion; Brain Injuries; Erythropoietin; Female; Glasgow Outcome Scale; Humans; Incidence; Male; Middle Aged; Outcome Assessment, Health Care; Proportional Hazards Models; Respiratory Distress Syndrome; Young Adult

Topics: COVID-19; Erythropoietin; Humans; Iron; Lung; Respiratory Distress Syndrome

Acute respiratory distress syndrome (ARDS) is a devastating disorder. Despite enormous efforts in clinical research, effective treatment options are lacking, and mortality rates remain unacceptably high.. A male patient with severe ARDS showed no clinical improvement with conventional therapies. Hence, an emergent experimental intervention was performed.. We performed intratracheal administration of autologous peripheral blood-derived mononuclear cells (PBMCs) and erythropoietin (EPO).. We found that after 2 days of initial PBMC/EPO application, lung function improved and extracorporeal membrane oxygenation (ECMO) support was reduced. Bronchoscopy and serum inflammatory markers revealed reduced inflammation. Additionally, serum concentration of miR-449a, b, c and miR-34a, a transient upregulation of E-cadherin and associated chromatin marks in PBMCs indicated airway epithelial differentiation. Extracellular vesicles from PBMCs demonstrated anti-inflammatory capacity in a TNF-α-mediated nuclear factor-x03BA;B in vitro assay. Despite improving respiratory function, the patient died of multisystem organ failure on day 38 of ECMO treatment.. This case report provides initial encouraging evidence to use locally instilled PBMC/EPO for treatment of severe refractory ARDS. The observed clinical improvement may partially be due to the anti-inflammatory effects of PBMC/EPO to promote tissue regeneration. Further studies are needed for more in-depth understanding of the underlying mechanisms of in vivo regeneration.

Topics: Cadherins; Cytokines; Down-Regulation; Erythropoietin; Extracorporeal Membrane Oxygenation; Fatal Outcome; Humans; Leukocytes, Mononuclear; Male; MicroRNAs; Multiple Organ Failure; Respiratory Distress Syndrome; Snail Family Transcription Factors; Transcription Factors; Transplantation, Autologous; Up-Regulation; Young Adult

To investigate the effect of exogenous erythro-poietin (EPO) administration on acute lung injury (ALI) in an experimental model of sodium taurodeoxycholate- induced acute necrotizing pancreatitis (ANP).. Forty-seven male Wistar albino rats were randomly divided into 7 groups: sham group (n = 5), 3 ANP groups (n = 7 each) and 3 EPO groups (n = 7 each). ANP was induced by retrograde infusion of 5% sodium taurodeoxycholate into the common bile duct. Rats in EPO groups received 1000 U/kg intramuscular EPO immediately after induction of ANP. Rats in ANP groups were given 1 mL normal saline instead. All animals were sacrificed at postoperative 24 h, 48 h and 72 h. Serum amilase, IL-2, IL-6 and lung tissue malondialdehyde (MDA) were measured. Pleural effusion volume and lung/body weight (LW/BW) ratios were calculated. Tissue levels of TNF-alpha, IL-2 and IL-6 were screened immunohistochemically. Additionally, ox-LDL accumulation was assessed with immune-fluorescent staining. Histopathological alterations in the lungs were also scored.. The mean pleural effusion volume, calculated LW/BW ratio, serum IL-6 and lung tissue MDA levels were significantly lower in EPO groups than in ANP groups. No statistically significant difference was observed in either serum or tissue values of IL-2 among the groups. The level of tumor necrosis factor-alpha (TNF-alpha) and IL-6 and accumulation of ox-LDL were evident in the lung tissues of ANP groups when compared to EPO groups, particularly at 72 h. Histopathological evaluation confirmed the improvement in lung injury parameters after exogenous EPO administration, particularly at 48 h and 72 h.. EPO administration leads to a significant decrease in ALI parameters by inhibiting polymorphonuclear leukocyte (PMNL) accumulation, decreasing the levels of proinflammatory cytokines in circulation, preserving microvascular endothelial cell integrity and reducing oxidative stress-associated lipid peroxidation and therefore, can be regarded as a cytoprotective agent in ANP-induced ALI.

Topics: Amylases; Animals; Body Weight; Disease Models, Animal; Erythropoietin; Interleukin-2; Interleukin-6; Lipoproteins, LDL; Lung; Male; Malondialdehyde; Neutrophils; Pancreatitis, Acute Necrotizing; Pleural Effusion; Pulmonary Alveoli; Rats; Rats, Wistar; Respiratory Distress Syndrome; Taurodeoxycholic Acid

Based on the findings that erythropoietin (EPO) has been proved to be a multiple functional cytokine to attenuate ischemia-reperfusion (I/R) injury in various organs such as brain, heart, and kidney in animals, this experiment was designed to evaluate the effect of pretreatment with recombined human erythropoietin (rhEPO) on I/R-induced lung injury.. Left lungs of rats underwent 90 min of ischemia and then were reperfused for up to 2 h. Animals were randomly divided into three experimental groups as sham group, I/R group, and rhEPO + I/R group (a single dose of rhEPO was injected intraperitoneally 3000 U/kg 24 h prior to operation). Lung injury was evaluated according to semi-quantitative analysis of microscopic changes, tissue polymorphonuclear neutrophils (PMNs) accumulation (myeloperoxidase (MPO) activity), and pulmonary microvascular permeability (Evan's blue dying method). Peripheral arterial and venous blood samples were obtained for blood-gas analysis after 5 min occlusion of right lung hilus at the end of reperfusion. The serum concentration of tumor necrosis factor (TNF)-alpha was also measured by the method of enzyme-linked immunosorbent assay.. Histological injury scoring revealed significantly lessened lung alveolus edema and neutrophils infiltration in the rhEPO pretreated group compared with I/R group (p < 0.05). The rhEPO pretreated animals exhibited markedly decreased lung microvascular permeability (p < 0.05) and myeloperoxidase activity (p < 0.05). Blood-gas analysis demonstrated that the pretreated animals had significantly ameliorated pulmonary oxygenation function (p < 0.05). The serum concentration of tumor necrosis factor-alpha in rhEPO pretreated group was markedly decreased compared with that of I/R group (p < 0.05).. Pretreatment with rhEPO appears to attenuate I/R-induced lung injury. This function is partly related with the capacity that rhEPO inhibits the accumulation of polymorphonuclear neutrophils in lung tissue and decreases the systematic expression of tumor necrosis factor-alpha.

Topics: Animals; Capillary Permeability; Erythropoietin; Lung; Male; Oxygen; Partial Pressure; Peroxidase; Rats; Rats, Sprague-Dawley; Recombinant Proteins; Reperfusion Injury; Respiratory Distress Syndrome; Tumor Necrosis Factor-alpha

Critically ill patients often develop anaemia which can be related to a number of factors. However, the exact causes of anaemia in many patients remain unexplained. We hypothesized that the relationship between erythropoietin (EPO) and haematocrit may be altered in critically ill patients.. Serum concentrations of EPO were serially determined by the ELISA method in 36 critically ill, non-hypoxaemic patients who stayed more than 7 days in the Intensive Care Unit, including 22 patients with sepsis and 14 without. Eighteen ambulatory patients with iron-deficiency anaemia served as a control group.. Two University Hospital Intensive Care Departments.. A significant inverse correlation between serum EPO and haematocrit levels was found in the control patients (r = -0.81, p < 0.001), but not in the critically ill patients (r = -0.09, NS), except in a subgroup of non-septic patients without renal failure (r = -0.61, p < 0.01).. EPO levels can be inappropriately low in critically ill patients, so that EPO deficiency may contribute to the development of anaemia in these patients. This phenomenon is observed not only in the presence of acute renal failure, but also in the presence of sepsis.

Topics: Acute Kidney Injury; Aged; Anemia, Hemolytic; Anemia, Iron-Deficiency; Case-Control Studies; Critical Illness; Enzyme-Linked Immunosorbent Assay; Erythropoietin; Female; Hematocrit; Humans; Intensive Care Units; Male; Middle Aged; Regression Analysis; Respiratory Distress Syndrome; Sepsis