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treatment of myocardial dysfunction in sepsis

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https://www.readbyqxmd.com/read/28526544/interleukin-18-gene-deletion-protects-against-sepsis-induced-cardiac-dysfunction-by-inhibiting-pp2a-activity
#1
Yoshitaka Okuhara, Shunichi Yokoe, Toshihiro Iwasaku, Akiyo Eguchi, Koichi Nishimura, Wen Li, Makiko Oboshi, Yoshiro Naito, Toshiaki Mano, Michio Asahi, Haruki Okamura, Tohru Masuyama, Shinichi Hirotani
BACKGROUND: Interleukin-18 (IL-18) neutralization protects against lipopolysaccharide (LPS)-induced injuries, including myocardial dysfunction. However, the mechanism is yet to be fully elucidated. The aim of the present study was to determine whether IL-18 gene deletion prevents sepsis-induced cardiac dysfunction and to elucidate the potential mechanisms underlying IL-18-mediated cardiotoxicity by LPS. METHODS AND RESULTS: Ten-week-old male wild-type (WT) and IL-18 knockout (IL-18 KO) mice were intraperitoneally administered LPS...
May 4, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28432312/growth-differentiation-factor-15-deficiency-augments-inflammatory-response-and-exacerbates-septic-heart-and-renal-injury-induced-by-lipopolysaccharide
#2
Palida Abulizi, Neruja Loganathan, Duo Zhao, Tina Mele, Yixin Zhang, Terry Zwiep, Kexiang Liu, Xiufen Zheng
Septic acute kidney injury (AKI) and myocardial dysfunction are leading causes of mortality with no accepted method of therapy. In this study we demonstrate the role of growth differentiating factor 15 (GDF15) in septic AKI and myocardial dysfunction using a murine lipopolysaccharide (LPS)-induced sepsis model and an in vitro cell culture system. Data show that GDF15 deficiency augments inflammatory response and exacerbates renal and cardiac injury induced by LPS, while over-expression of GDF15 protects the kidney and heart from LPS-induced organ dysfunction...
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28420138/adjustment-of-dysregulated-ceramide-metabolism-in-a-murine-model-of-sepsis-induced-cardiac-dysfunction
#3
Ha-Yeun Chung, Anna S Kollmey, Andrea Schrepper, Matthias Kohl, Markus F Bläss, Sebastian N Stehr, Amelie Lupp, Markus H Gräler, Ralf A Claus
Cardiac dysfunction, in particular of the left ventricle, is a common and early event in sepsis, and is strongly associated with an increase in patients' mortality. Acid sphingomyelinase (SMPD1)-the principal regulator for rapid and transient generation of the lipid mediator ceramide-is involved in both the regulation of host response in sepsis as well as in the pathogenesis of chronic heart failure. This study determined the degree and the potential role to which SMPD1 and its modulation affect sepsis-induced cardiomyopathy using both genetically deficient and pharmacologically-treated animals in a polymicrobial sepsis model...
April 15, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28333102/biological-effect-of-licochalcone-c-on-the-regulation-of-pi3k-akt-enos-and-nf-%C3%AE%C2%BAb-inos-no-signaling-pathways-in-h9c2-cells-in-response-to-lps-stimulation
#4
Sara Franceschelli, Mirko Pesce, Alessio Ferrone, Daniela Maria Pia Gatta, Antonia Patruno, Maria Anna De Lutiis, José Luis Quiles, Alfredo Grilli, Mario Felaco, Lorenza Speranza
Polyphenols compounds are a group molecules present in many plants. They have antioxidant properties and can also be helpful in the management of sepsis. Licochalcone C (LicoC), a constituent of Glycyrrhiza glabra, has various biological and pharmacological properties. In saying this, the effect of LicoC on the inflammatory response that characterizes septic myocardial dysfunction is poorly understood. The aim of this study was to determine whether LicoC exhibits anti-inflammatory properties on H9c2 cells that are stimulated with lipopolysaccharide...
March 23, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28168403/carbon-monoxide-releasing-molecule-3-improves-myocardial-function-in-mice-with-sepsis-by-inhibiting-nlrp3-inflammasome-activation-in-cardiac-fibroblasts
#5
Wenbo Zhang, Aibin Tao, Ting Lan, Gediminas Cepinskas, Raymond Kao, Claudio M Martin, Tao Rui
The NLRP3 inflammasome is an intracellular multiple-protein complex that controls the maturation and release of interleukin (IL)-1β and IL-18. Endogenous carbon monoxide (CO) is anti-inflammatory. The aim of this study was to assess the effects/mechanisms of CO-releasing molecule-3 (CORM-3)-dependent modulation of the NLRP3 inflammasome in cardiac fibroblasts (CF) and its effect on myocardial function in sepsis. CF were treated with CORM-3 or inactive CORM-3 (iCORM-3) before NLRP3 inflammasome priming with lipopolysaccharides (LPS) or following activation with adenosine triphosphate (ATP)...
March 2017: Basic Research in Cardiology
https://www.readbyqxmd.com/read/28147298/microrna-135a-is-up-regulated-and-aggravates-myocardial-depression-in-sepsis-via-regulating-p38-mapk-nf-%C3%AE%C2%BAb-pathway
#6
Ge Zheng, Minli Pan, Weimin Jin, Guoxin Jin, Yumao Huang
MicroRNA-135a (miR-135a) is implicated in the pathological processes of several cancers. However, the roles and regulatory mechanism of miR-135a in sepsis-induced myocardial depression (MD) remain largely unknown. In this study, the serum of patients with sepsis and healthy controls was obtained. The miR-135a expression was then measured. Then lentiviruses (miR-135a mimic, inhibitor and scramble control) were transfected into BALB/c mice. After 4days of transfection, polymicrobial sepsis model was established by cecal ligation and puncture (CLP) surgery...
April 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/27973394/abnormal-mitochondrial-camp-pka-signaling-is-involved-in-sepsis-induced-mitochondrial-and-myocardial-dysfunction
#7
Remi Neviere, Florian Delguste, Arthur Durand, Jocelyn Inamo, Eric Boulanger, Sebastien Preau
Adrenergic receptors couple to Gs-proteins leading to transmembrane adenylyl cyclase activation and cytosolic cyclic adenosine monophosphate (cAMP) production. Cyclic AMP is also produced in the mitochondrial matrix, where it regulates respiration through protein kinase A (PKA)-dependent phosphorylation of respiratory chain complexes. We hypothesized that a blunted mitochondrial cAMP-PKA pathway would participate in sepsis-induced heart dysfunction. Adult male mice were subjected to intra-abdominal sepsis. Mitochondrial respiration of cardiac fibers and myocardial contractile performance were evaluated in response to 8Br-cAMP, PKA inhibition (H89), soluble adenylyl cyclase inhibition (KH7), and phosphodiesterase inhibition (IBMX; BAY60-7550)...
December 10, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27908339/vasopressors-and-inotropes-in-sepsis
#8
REVIEW
Leeanne Stratton, David A Berlin, John E Arbo
Vasopressor and inotropes are beneficial in shock states. Norepinephrine is considered the first-line vasopressor for patients with sepsis-associated hypotension. Dobutamine is considered the first-line inotrope in sepsis, and should be considered for patients with evidence of myocardial dysfunction or ongoing signs of hypoperfusion. Vasopressor and inotrope therapy has complex effects that are often difficult to predict; emergency providers should consider the physiology and clinical trial data. It is essential to continually reevaluate the patient to determine if the selected treatment is having the intended result...
February 2017: Emergency Medicine Clinics of North America
https://www.readbyqxmd.com/read/27716530/naringin-protects-against-lipopolysaccharide-induced-cardiac-injury-in-mice
#9
Liu Xianchu, Professor Zheng Lan, Li Qiufang, Liu Yi, Ruan Xiangcheng, Hou Wenqi, Ding Yang
Previous research has demonstrated that lipopolysaccharide (LPS) can induce sepsis and lead to myocardial dysfunction. Naringin has various biological activities in LPS-induced sepsis. In this study, our aim was to investigate the effects of Naringin on LPS-induced cardiac injury and clarify its potential mechanism. We found that in vivo treatment with Naringin significantly ameliorated body weight loss, and attenuated cardiac histopathological changes after LPS challenge. Furthermore, Naringin inhibited LPS-induced increase of TNF-α, IL-1β and IL-6 activities to alleviate inflammatory response in heart...
December 2016: Environmental Toxicology and Pharmacology
https://www.readbyqxmd.com/read/27709263/refractory-septic-shock-in-children-a-european-society-of-paediatric-and-neonatal-intensive-care-definition
#10
Luc Morin, Samiran Ray, Clare Wilson, Solenn Remy, Mohamed Rida Benissa, Nicolaas J G Jansen, Etienne Javouhey, Mark J Peters, Martin Kneyber, Daniele De Luca, Simon Nadel, Luregn Jan Schlapbach, Graeme Maclaren, Pierre Tissieres
PURPOSE: Although overall paediatric septic shock mortality is decreasing, refractory septic shock (RSS) is still associated with high mortality. A definition for RSS is urgently needed to facilitate earlier identification and treatment. We aim to establish a European society of paediatric and neonatal intensive care (ESPNIC) experts' definition of paediatric RSS. METHODS: We conducted a two-round Delphi study followed by an observational multicentre retrospective study...
December 2016: Intensive Care Medicine
https://www.readbyqxmd.com/read/27620887/cardiac-electrical-and-structural-changes-during-bacterial-infection-an-instructive-model-to-study-cardiac-dysfunction-in-sepsis
#11
Michael A Makara, Ky V Hoang, Latha P Ganesan, Elliot D Crouser, John S Gunn, Joanne Turner, Larry S Schlesinger, Peter J Mohler, Murugesan V S Rajaram
BACKGROUND: Sepsis patients with cardiac dysfunction have significantly higher mortality. Although several pathways are associated with myocardial damage in sepsis, the precise cause(s) remains unclear and treatment options are limited. This study was designed to develop a new model to investigate the early events of cardiac damage during sepsis progression. METHODS AND RESULTS: Francisella tularensis subspecies novicida (Ft.n) is a Gram-negative intracellular pathogen causing severe sepsis syndrome in mice...
September 12, 2016: Journal of the American Heart Association
https://www.readbyqxmd.com/read/27569679/diastolic-dysfunction-in-the-critically-ill-patient
#12
J C Suárez, P López, J Mancebo, L Zapata
Left ventricular diastolic dysfunction is a common finding in critically ill patients. It is characterized by a progressive deterioration of the relaxation and the compliance of the left ventricle. Two-dimensional and Doppler echocardiography is a cornerstone in its diagnosis. Acute pulmonary edema associated with hypertensive crisis is the most frequent presentation of diastolic dysfunction critically ill patients. Myocardial ischemia, sepsis and weaning failure from mechanical ventilation also may be associated with diastolic dysfunction...
November 2016: Medicina Intensiva
https://www.readbyqxmd.com/read/27434571/-the-role-of-mitochondrial-permeability-transition-pore-in-the-occurrence-of-septic-myocardial-depression
#13
REVIEW
Shanzi Jin, Sheng Wang
Sepsis is defined as life-threatening organ dysfunction caused by a dys-regulated host response to infection and septic myocardial depression (SMD) is a common complication. Pathogenesis of SMD is complicated and there is lack of specific treatment. Mitochondrial damage is an important pathological basis of SMD, and mitochondrial permeability transition pore (MPTP) plays an important role in maintaining the normal structure and function of the mitochondria. The change of MPTP during sepsis is summarized in this review so as to reveal the significant mechanism of MPTP in the occurrence of SMD...
August 2016: Zhonghua Wei Zhong Bing Ji Jiu Yi Xue
https://www.readbyqxmd.com/read/27355401/beneficial-effect-of-intermedin-1-53-in-septic-shock-rats-contributions-of-rho-kinase-and-bkca-pathway-mediated-improvement-in-cardiac-function
#14
Tao Li, Zhu Yu, Wu Huiling, Wu Yue, Zhang Jie, Peng Xiaoyong, Zang Jiatao, Xiang Xinming, Liangming Liu
OBJECTIVE: Intermedin (IMD) is a calcitonin gene-related peptide shown to have a protective effect on myocardial function in ischemia-reperfusion injury. Whether IMD has beneficial effect in severe sepsis and septic shock (and its underlying mechanisms) is not known. METHODS: We induced septic shock using cecal ligation and puncture (CLP). We focused on the potential beneficial effect of IMD1-53 on cardiac papillary muscle and cardiomyocytes against septic shock and its relationship with protection of cardiac function...
June 28, 2016: Shock
https://www.readbyqxmd.com/read/27338886/%C3%AE-blockers-in-sepsis-protocol-for-a-systematic-review-and-meta-analysis-of-randomised-control-trials
#15
Erick H Duan, Simon J W Oczkowski, Emilie Belley-Cote, Richard Whitlock, Francois Lamontagne, Phillip J Devereaux, Deborah J Cook
INTRODUCTION: Sepsis is a common and deadly complication of infection. As part of the host response, sympathetic stimulation can result in septic myocardial depression, and metabolic, haematological and immunological dysfunction. Administration of β-blockers may attenuate this pathophysiological response to infection, but the effects on clinical outcomes are unknown. The objective of this systematic review is to determine the efficacy and safety of β-blockers in adults with sepsis using data from randomised control trials...
2016: BMJ Open
https://www.readbyqxmd.com/read/27317946/north-american-ginseng-inhibits-myocardial-nox2-erk1-2-signaling-and-tumor-necrosis-factor-%C3%AE-expression-in-endotoxemia
#16
Yan Wu, Chaoyi Qin, Xiangru Lu, Jocelyn Marchiori, Qingping Feng
Sepsis is a systemic inflammatory response to infection with a high mortality but has no specific treatment despite decades of research. North American (NA) ginseng (Panax quinquefolius) is a popular natural health product with anti-oxidant and anti-inflammatory properties. The aim of the present study was to investigate the effects of NA ginseng on pro-inflammatory cytokine expression and cardiac function in endotoxemia, a model of sepsis. Mice were challenged with lipopolysaccharide (LPS) to induce endotoxemia...
September 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/27168089/levosimendan-new-indications-and-evidence-for-reduction-in-perioperative-mortality
#17
Antonio Pisano, Giacomo Monti, Giovanni Landoni
PURPOSE OF REVIEW: In the last years, the perioperative use of levosimendan in cardiac surgery patients is spreading. Moreover, newer indications have been suggested such as the treatment of sepsis-associated myocardial dysfunction. In the present review, we discuss the most recent evidences in these settings. RECENT FINDINGS: Levosimendan has been seemingly confirmed to reduce mortality in patients undergoing cardiac surgery. In particular, it appears to be the only inotropic drug to have a favorable effect on survival in any clinical setting...
August 2016: Current Opinion in Anaesthesiology
https://www.readbyqxmd.com/read/27098997/attenuation-of-the-lps-induced-erk-mediated-upregulation-of-fibrosis-related-factors-fgf-2-upa-mmp-2-and-mmp-9-by-carthamus-tinctorius-l-in-cardiomyoblasts
#18
Chien-Kuo Han, Yun-Chen Tien, Dennis Jine-Yuan Hsieh, Tsung-Jung Ho, Chao-Hung Lai, Yu-Lan Yeh, Cecilia Hsuan Day, Chia-Yao Shen, Hsi-Hsien Hsu, Jing-Ying Lin, Chih-Yang Huang
Severe and potentially fatal hypotension and cardiac contractile dysfunction are common symptoms in patients with sepsis. LPS was previously found to dramatically upregulate expression of fibrosis-related factors FGF-2, uPA, MMP-2, and MMP-9 in primary cardiac fibroblasts. MMPs are capable of denaturing and degrading fibrillar collagens and other components of the extracellular matrix (ECM). Studies have shown that dysregulation of expression of MMPs is associated with development of myocardial extracellular matrix remodeling and cardiac fibrosis, which contribute to progression of heart failure...
March 2017: Environmental Toxicology
https://www.readbyqxmd.com/read/26982508/neural-control-of-inflammation-implications-for-perioperative-and-critical-care
#19
REVIEW
Benjamin E Steinberg, Eva Sundman, Niccolo Terrando, Lars I Eriksson, Peder S Olofsson
Inflammation and immunity are regulated by neural reflexes. Recent basic science research has demonstrated that a neural reflex, termed the inflammatory reflex, modulates systemic and regional inflammation in a multiplicity of clinical conditions encountered in perioperative medicine and critical care. In this review, the authors describe the anatomic and physiologic basis of the inflammatory reflex and review the evidence implicating this pathway in the modulation of sepsis, ventilator-induced lung injury, postoperative cognitive dysfunction, myocardial ischemia-reperfusion injury, and traumatic hemorrhage...
May 2016: Anesthesiology
https://www.readbyqxmd.com/read/26858715/macrophage-migration-inhibitory-factor-in-clinical-kidney-disease
#20
REVIEW
Annette Bruchfeld, Mårten Wendt, Edmund J Miller
Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine implicated in acute and chronic inflammatory conditions, including sepsis, autoimmune disease, atherogenesis, plaque instability, and pulmonary arterial hypertension. MIF in plasma and urine is significantly elevated in patients with acute kidney injury (AKI) and elevated MIF in serum is associated with markers of oxidative stress, endothelial dysfunction, arterial stiffness, and markers of myocardial damage in chronic kidney disease (CKD)...
2016: Frontiers in Immunology
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