Hydrogen sulfide ameliorates cardiovascular dysfunction induced by cecal ligation and puncture in rats

2015 ◽  
Vol 34 (10) ◽  
pp. 953-964 ◽  
Author(s):  
RS Abdelrahman ◽  
MS El-Awady ◽  
MA Nader ◽  
EM Ammar
Keyword(s):  
Hydrogen Sulfide ◽  
Vascular Reactivity ◽  
Troponin I ◽  
Histopathological Examination ◽  
Vascular Dysfunction ◽  
Cecal Ligation ◽  
Cecal Ligation And Puncture ◽  
Cardiovascular Dysfunction ◽  
Sodium Hydrosulfide ◽  
Creatine Kinase Mb

Hydrogen sulfide (H2S) is an endogenously produced gaseous messenger that participates in regulation of cardiovascular functions. This study evaluates the possible protective effect of H2S in cardiovascular dysfunction induced by cecal ligation and puncture (CLP) in rats. After 24 h of induction of CLP, heart rate (HR), mortality, cardiac and inflammation biomarkers (creatine kinase-MB (CK-MB) isozyme, cardiac troponin I (cTnI), C-reactive protein (CRP), and lactate dehydrogenase (LDH)), in vitro vascular reactivity, histopathological examination, and oxidative biomarkers (malondialdehyde (MDA), reduced glutathione (GSH), and superoxide dismutase (SOD)) were determined. CLP induced elevations in HR, mortality, serum CK-MB, cTnI, CRP, and LDH, in addition to impaired aortic contraction to potassium chloride and phenylephrine and relaxation to acetylcholine without affecting sodium nitroprusside responses. Moreover, CLP increased cardiac and aortic MDA and decreased SOD, without affecting GSH and caused a marked subserosal and interstitial inflammation in endocardium. Sodium hydrosulfide, but not the irreversible inhibitor of H2S synthesis dl-propargyl glycine, protected against CLP-induced changes in HR, mortality, cardiac and inflammatory biomarkers, oxidative stress, and myocardium histopathological changes without affecting vascular dysfunction. Our results confirm that H2S can attenuate CLP-induced cardiac, but not vascular, dysfunction possibly through its anti-inflammatory and antioxidant effects.

Role of hydrogen sulfide in cecal ligation and puncture-induced sepsis in the mouse

2006 ◽  
Vol 290 (6) ◽  
pp. L1193-L1201 ◽  
Author(s):  
Huili Zhang ◽  
Liang Zhi ◽  
Philip K. Moore ◽  
Madhav Bhatia
Keyword(s):  
Hydrogen Sulfide ◽  
Systemic Inflammation ◽  
Mammalian Cells ◽  
Cecal Ligation ◽  
Organ Injury ◽  
Sham Operation ◽  
Myeloperoxidase Activity ◽  
Cecal Ligation And Puncture ◽  
Sodium Hydrosulfide

Endogenous hydrogen sulfide (H2S) is naturally synthesized in various types of mammalian cells from l-cysteine in a reaction catalyzed by two enzymes, cystathionine-γ-lyase (CSE) and/or cystathionine-β-synthase. The latest studies have implied that H2S functions as a vasodilator and neurotransmitter. However, so far there is little information about the role played by H2S in systemic inflammation such as sepsis. Thus the aim of this study was to investigate the potential role of endogenous H2S in cecal ligation and puncture (CLP)-induced sepsis. Male Swiss mice were subjected to CLP-induced sepsis and treated with saline (ip), dl-propargylglycine (PAG, 50 mg/kg ip), a CSE inhibitor, or sodium hydrosulfide (NaHS; 10 mg/kg ip). PAG was administered either 1 h before or 1 h after the induction of sepsis, whereas NaHS was given at the same time of CLP. CLP-induced sepsis significantly increased the plasma H2S level and the liver H2S synthesis 8 h after CLP compared with sham operation. Induction of sepsis also resulted in a significant upregulation of CSE mRNA in liver. On the other hand, prophylactic as well as therapeutic administration of PAG significantly reduced sepsis-associated systemic inflammation, as evidenced by myeloperoxidase activity and histological changes in lung and liver, and attenuated the mortality of CLP-induced sepsis. Injection of NaHS significantly aggravated sepsis-associated systemic inflammation. Therefore, the effect of inhibition of H2S formation and administration of NaHS suggests that H2S plays a proinflammatory role in regulating the severity of sepsis and associated organ injury.

scholarly journals Diminished responsiveness to dobutamine as an inotrope in mice with cecal ligation and puncture-induced sepsis: attribution to phosphodiesterase 4 upregulation

2017 ◽  
Vol 312 (6) ◽  
pp. H1224-H1237 ◽  
Author(s):  
Mari Sakai ◽  
Tokiko Suzuki ◽  
Kengo Tomita ◽  
Shigeyuki Yamashita ◽  
Sailesh Palikhe ◽  
...  
Keyword(s):  
Septic Shock ◽  
Troponin I ◽  
Therapeutic Option ◽  
Cecal Ligation ◽  
Ventricular Myocardium ◽  
Left Ventricular ◽  
Fluid Replacement ◽  
Cecal Ligation And Puncture ◽  
Inotropic Effects ◽  
Effective Manner

Dobutamine has been used in septic shock for many years as an only inotrope, but its benefit has been questioned. We weighed the effects of dobutamine and milrinone as inotropes in mice with cecal ligation and puncture (CLP)-induced polymicrobial sepsis. CLP-induced septic mice exhibited significant cardiac inflammation, as indicated by greatly increased mRNAs of proinflammatory cytokines and robust infiltration of inflammatory cells in the ventricular myocardium. Elevations of plasma cardiac troponin-I showed cardiac injury in CLP mice. Noninvasive echocardiographic assessment of cardiac function revealed that despite preserved left ventricular function in the presence of fluid replacement, the dobutamine inotropic response was significantly impaired in CLP mice compared with sham-operated controls. By contrast, milrinone exerted inotropic effects in sham-operated and CLP mice in an equally effective manner. Surface expression levels of β1-adrenoceptors and α-subunits of three main G protein families in the myocardium were unaffected by CLP-induced sepsis. Plasma cAMP levels were significantly elevated in both sham-operated and CLP mice in response to milrinone but only in sham-operated controls in response to dobutamine. Of phosphodiesterase (PDE) isoforms, PDE4D, but not PDE3A, both of which are responsible for cardiac cAMP hydrolysis, was significantly upregulated in CLP mouse myocardium. We define a novel mechanism for the impaired responsiveness to dobutamine as an inotrope in sepsis, and understanding the role of PDE4D in modulating cardiac functional responsiveness in sepsis may open the potential of a PDE4D-targeted therapeutic option in septic patients with low cardiac output who have a need for inotropic support. NEW & NOTEWORTHY Advisability of the usefulness of dobutamine in septic shock management is limited. Here, we reveal that the effect of dobutamine as a positive inotrope is impaired in mice with cecal ligation and puncture-induced sepsis without changes in cardiac β1-adrenoceptor signaling as a result of cAMP breakdown achieved by upregulated phosphodiesterase 4D.

scholarly journals Lactate as a Potential Biomarker of Sepsis in a Rat Cecal Ligation and Puncture Model

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Xiaozhu Zhai ◽  
Zhengfei Yang ◽  
Guanghui Zheng ◽  
Tao Yu ◽  
Peng Wang ◽  
...  
Keyword(s):  
Troponin I ◽  
Cecal Ligation ◽  
Weight Ratio ◽  
High Mobility ◽  
Dry Weight ◽  
Cecal Ligation And Puncture ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Potential Biomarker ◽  
Puncture Model

We attempted to investigate whether blood lactate is a useful biomarker for sepsis in a rat cecal ligation and puncture (CLP) model. Male Sprague-Dawley rats underwent approximately 75% cecum ligation and two punctures to induce high-grade sepsis. A lactate of 1.64 mmol/L (Youden score of 0.722) was selected as the best cutoff value to predict the onset of sepsis after CLP exposure; 46 of 50 rats who survived 24 hours after the CLP were divided into the L group (lactate < 1.64 mmol/L) and M group (lactate ≥ 1.64 mmol/L). In the M group, the animals had significantly higher murine sepsis scores and none survived 5 days post-CLP, and the rate of validated septic animals, serum procalcitonin, high mobility group box 1, blood urea nitrogen, alanine transaminase, cardiac troponin I, and the wet-to-dry weight ratio were significantly higher compared to the L group. Worsen PaO2/FiO2, microcirculations, and mean arterial pressure were observed in the M group. More severe damage in major organs was confirmed by histopathological scores in the M group compared with the L group. In conclusion, lactate ≥ 1.64 mmol/L might serve as a potential biomarker to identify the onset of sepsis in a rat CLP model.

Hydrogen sulfide acts as an inflammatory mediator in cecal ligation and puncture-induced sepsis in mice by upregulating the production of cytokines and chemokines via NF-κB

2007 ◽  
Vol 292 (4) ◽  
pp. L960-L971 ◽  
Author(s):  
Huili Zhang ◽  
Liang Zhi ◽  
Shabbir Moochhala ◽  
Philip K. Moore ◽  
Madhav Bhatia
Keyword(s):  
Hydrogen Sulfide ◽  
Systemic Inflammation ◽  
Lung Inflammation ◽  
Cecal Ligation ◽  
Cecal Ligation And Puncture ◽  
Protein Levels ◽  
Proinflammatory Mediators ◽  
Inflammatory Conditions ◽  
Cytokines And Chemokines ◽  
Inflammatory Protein

Recent studies have implied that hydrogen sulfide (H2S) plays a crucial role in several inflammatory conditions. However, so far little is known about the mechanism by which H2S provokes the inflammatory response in sepsis. Thus the aim of this study was to investigate if H2S regulates sepsis-associated systemic inflammation and production of proinflammatory mediators via the activation of NF-κB. Male Swiss mice were subjected to cecal ligation and puncture (CLP)-induced sepsis and treated with dl-propargylglycine (PAG; 50 mg/kg ip), NaHS (10 mg/kg ip), or saline. PAG, an inhibitor of H2S formation, was administered either 1 h before or 1 h after CLP, whereas NaHS, an H2S donor, was given at the time of CLP. Some normal mice were given NaHS (10 mg/kg ip) to induce lung inflammation with or without pretreatment with the NF-κB inhibitor BAY 11-7082. Eight hours after CLP, both prophylactic and therapeutic administration of PAG significantly reduced the mRNA and protein levels of IL-1β, IL-6, TNF-α, monocyte chemotactic protein-1, and macrophage inflammatory protein-2 in lung and liver coupled with decreased activation and translocation of NF-κB in lung and liver. Inhibition of H2S formation also significantly reduced lung permeability and plasma alanine aminotransferase activity. In contrast, injection of NaHS significantly aggravated sepsis-associated systemic inflammation and increased NF-κB activation. In addition, H2S-induced lung inflammation was blocked by BAY 11-7082. Therefore, H2S upregulates the production of proinflammatory mediators and exacerbates the systemic inflammation in sepsis through a mechanism involving NF-κB activation.

Metabolic syndrome improves cardiovascular dysfunction and survival during cecal ligation and puncture-induced mild sepsis in mice

Life Sciences ◽  
2021 ◽  
pp. 120033
Author(s):  
Raquel Pires Nakama ◽  
Aparecida Donizette Malvezi ◽  
Maria Isabel Lovo-Martins ◽  
Lucas Felipe dos Santos ◽  
Ana Paula Canizares Cardoso ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Cecal Ligation ◽  
Cecal Ligation And Puncture ◽  
Cardiovascular Dysfunction

Endogenous hydrogen sulfide regulates leukocyte trafficking in cecal ligation and puncture-induced sepsis

2007 ◽  
Vol 82 (4) ◽  
pp. 894-905 ◽  
Author(s):  
Huili Zhang ◽  
Liang Zhi ◽  
Shabbir M. Moochhala ◽  
Philip Keith Moore ◽  
Madhav Bhatia
Keyword(s):  
Hydrogen Sulfide ◽  
Cecal Ligation ◽  
Leukocyte Trafficking ◽  
Cecal Ligation And Puncture

scholarly journals Cardioprotective Effects of Tualang Honey: Amelioration of Cholesterol and Cardiac Enzymes Levels

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Md. Ibrahim Khalil ◽  
E. M. Tanvir ◽  
Rizwana Afroz ◽  
Siti Amrah Sulaiman ◽  
Siew Hua Gan
Keyword(s):  
Lipid Peroxidation ◽  
Troponin I ◽  
Histopathological Examination ◽  
Antioxidant Defense System ◽  
Protective Effects ◽  
Marker Enzymes ◽  
Cardiac Marker ◽  
Creatine Kinase Mb ◽  
Cardioprotective Effects ◽  
Tualang Honey

The present study was designed to investigate the cardioprotective effects of Malaysian Tualang honey against isoproterenol- (ISO-) induced myocardial infarction (MI) in rats by investigating changes in the levels of cardiac marker enzymes, cardiac troponin I (cTnI), triglycerides (TG), total cholesterol (TC), lipid peroxidation (LPO) products, and antioxidant defense system combined with histopathological examination. Male albino Wistar rats (n= 40) were pretreated orally with Tualang honey (3 g/kg/day) for 45 days. Subcutaneous injection of ISO (85 mg/kg in saline) for two consecutive days caused a significant increase in serum cardiac marker enzymes (creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH), and aspartate transaminase (AST)), cTnI, serum TC, and TG levels. In addition, ISO-induced myocardial injury was confirmed by a significant increase in heart lipid peroxidation (LPO) products (TBARS) and a significant decrease in antioxidant enzymes (SOD, GPx, GRx, and GST). Pretreatment of ischemic rats with Tualang honey conferred significant protective effects on all of the investigated biochemical parameters. The biochemical findings were further confirmed by histopathological examination in both Tualang-honey-pretreated and ISO-treated hearts. The present study demonstrates that Tualang honey confers cardioprotective effects on ISO-induced oxidative stress by contributing to endogenous antioxidant enzyme activity via inhibition of lipid peroxidation.

Protective Effect of Taraxasterol Against Myocardial Damage Caused by Sepsis Through Inhibition of Toll-Like Receptor 4/Nuclear Factor-Kappa B Signaling Pathway

2021 ◽  
Vol 19 (3) ◽  
pp. 339-344
Author(s):  
Shuquan Wang ◽  
Xuhui Tang
Keyword(s):  
Signaling Pathway ◽  
Troponin I ◽  
Morphological Changes ◽  
Cardiac Injury ◽  
Cecal Ligation ◽  
Myocardial Damage ◽  
Protective Effects ◽  
Toll Like Receptor 4 ◽  
Membrane Rupture ◽  
Creatine Kinase Mb

Taraxasterol exerts protective effects against vascular or neuroinflammation and hepatic injury. However, its role on myocardial damage caused by sepsis has not been thoroughly investigated. Myocardial tissues of septic rats - established by cecal ligation and puncture - show a disordered myocardial fiber arrangement, edema, nuclear membrane rupture, and inflammatory cell infiltration. Administration of taraxasterol to these rats attenuated the morphological changes in the myocardial tissues. Biomarkers of cardiac injury in sepsis such as cardiac troponin I, creatine kinase-MB, and lactic acid dehydrogenase were elevated in the plasma of septic rats, and the administration of taraxasterol decreased the rise in these biomarkers. Also, taraxasterol attenuated increase in the levels of inflammatory cytokines in myocardial tissues of septic rats. Based on the evaluation of changes in the mediators of TLR4/NF-κB signaling pathway in sepsis and following treatment with taraxasterol led us to conclude that taraxasterol alleviates myocardial damage in septic rats through inhibition of the TLR4/NF-κB signaling pathway.

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