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 MicroRNA-495 serves as a diagnostic biomarker in patients with sepsis and regulates sepsis-induced inflammation and cardiac dysfunction

2019 ◽  
Vol 24 (1) ◽  
Author(s):  
Hailei Guo ◽  
Liying Tang ◽  
Jianjun Xu ◽  
Cai Lin ◽  
Xiangwei Ling ◽  
...  
Keyword(s):  
Sofa Score ◽  
Cardiac Dysfunction ◽  
Troponin I ◽  
Cecal Ligation ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Apache Ii Score ◽  
Diagnostic Biomarker ◽  
Blood Cytokines ◽  
Tnf Α

Abstract Background Sepsis leads to severe inflammatory and cardiac dysfunction. This study aimed to explore the clinical value of miR-495 in sepsis, as well as its role in sepsis-induced inflammation and cardiac dysfunction. Methods 105 sepsis patients were recruited; receiver operating characteristic (ROC) curve was plotted to assess the diagnostic value of miR-495 in sepsis. A model of sepsis in rats was created via performing cecal ligation and puncture (CLP). After modeling, the cardiac function, including left ventricular systolic pressure (LVSP), left ventricular end diastolic pressure (LVEDP) and maximum rate of rise/fall of left ventricle pressure (± dp/dtmax), and serum cardiac troponin I (CTn-I), creative kinase isoenzyme MB (CK-MB) were detected. The blood cytokines levels including TNF-α, IL-6, IL-1β were also measured. Quantitative real-time PCR (qRT-PCR) was used for the measurement of the expression level of miR-495. Results MiR-495 was significantly downregulated in sepsis patients, especially patients who suffered from septic shock (SS). MiR-495 expression was negatively associated with Scr, WBC, CRP, PCT, APACHE II score and SOFA score. MiR-495 could distinguish patients with SS from non-SS patients. MiR-495 and SOFA score were better indictors for the occurrence of cardiac dysfunction in sepsis patients. In CLP-induced sepsis model. CLP rats experienced deterioration of LVSP, LVEDP, ± dp/dtmax, and had a rise in serum CTn-I, CK-MB, TNF-α, IL-6 and IL-1β, which were improved by miR-495 agomir injection. Conclusions MiR-495 might be a potential diagnostic biomarker for sepsis patients, and overexpression of miR-495 alleviated sepsis-induced inflammation and cardiac dysfunction.

scholarly journals STAT1-DEFICIENT MICE ARE RESISTANT TO CECAL LIGATION AND PUNCTURE–INDUCED SEPTIC SHOCK

Shock ◽  
2012 ◽  
Vol 38 (4) ◽  
pp. 395-402 ◽  
Author(s):  
Daniela Herzig ◽  
Geping Fang ◽  
Tracy E. Toliver-Kinsky ◽  
Yin Guo ◽  
Julia Bohannon ◽  
...  
Keyword(s):  
Septic Shock ◽  
Cecal Ligation ◽  
Cecal Ligation And Puncture ◽  
Deficient Mice

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.

Abstract 11685: Early Myocardial Gene Expression Profiling After Deep Hypothermic Circulatory Arrest Reveals Ontogenetic Adaptive Mechanisms Underlying Ischemia-Reperfusion Tolerance in the Swine

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Miki Yamada ◽  
Amir Sheikh ◽  
Kevin Collins ◽  
James Frederiksen ◽  
George Quick ◽  
...  
Keyword(s):  
Myocardial Injury ◽  
Troponin I ◽  
Ischemia Reperfusion ◽  
Circulatory Arrest ◽  
Expression Patterns ◽  
Ventricular Myocardium ◽  
Deep Hypothermic Circulatory Arrest ◽  
Left Ventricular ◽  
Hypothermic Circulatory Arrest ◽  
Left Ventricular Myocardium

Previous studies suggest that immature hearts are more tolerant to ischemia than adult myocardium; whether differences exist during ontogenic development in severity of global myocardial ischemia/reperfusion (I/R) injury associated with cardiac surgery remains unknown. We employed swine models of deep hypothermic circulatory arrest (DHCA) to test the hypothesis that early differential regulation of cardioprotective genes is associated with increased tolerance of neonatal myocardium to surgical I/R. Male neonatal and adult pigs were randomized to DHCA or sham (N=5-14/group). DHCA animals underwent cardiopulmonary bypass (18°C), DHCA 60 min, and were recovered for 3h. Severity of perioperative myocardial injury was determined biochemically (Troponin I) and echocardiographically. Transcript levels were quantified in left ventricular myocardium using Affymetrix Porcine Genome arrays, followed by differential expression and pathway analysis. A 2-fold increase in severity of perioperative myocardial injury was found in adult pigs (Fig.A). Of 596 transcripts differentially expressed in neonates (≥1.5-fold change, DHCA vs. sham, FDR<0.05), 53 were shared with adults (Fig.B). Among them, divergent expression patterns were found for oxysterol binding protein-like 6 (down-regulated in adults up-regulated in neonates) and bromodomain adjacent to zinc finger domain 2B (up-regulated in adults - down-regulated in neonates). Top transcripts uniquely upregulated in neonates but unchanged in adults were the apoptosis inhibitor baculoviral IAP repeat containing 2, and signal transducer and activator of transcription 3. mTOR signaling and p53 signaling were the top canonical pathways deregulated in adults and neonates, respectively. A high resistance to surgical I/R injury in neonatal vs adult swine heart is correlated with robust differences in early transcriptional programs, suggesting the involvement of fundamental adaptive ontogenetic processes.

scholarly journals Troponin Testing for Assessing Sepsis-Induced Myocardial Dysfunction in Patients with Septic Shock

2019 ◽  
Vol 8 (2) ◽  
pp. 239 ◽  
Author(s):  
June-sung Kim ◽  
Muyeol Kim ◽  
Youn-Jung Kim ◽  
Seung Mok Ryoo ◽  
Chang Hwan Sohn ◽  
...  
Keyword(s):  
Septic Shock ◽  
Confidence Interval ◽  
Diastolic Dysfunction ◽  
Odds Ratio ◽  
Troponin I ◽  
Myocardial Dysfunction ◽  
Systolic Dysfunction ◽  
Area Under The Curve ◽  
Regional Wall Motion ◽  
Left Ventricular

(1) Background: Myocardial dysfunction in patients with sepsis is not an uncommon phenomenon, yet reported results are conflicting and there is no objective definition. Measurement of troponin may reflect the state of the heart and may correlate with echocardiographically derived data. This study aimed to evaluate the role of admission and peak troponin-I testing for the identification of sepsis-induced myocardial dysfunction (SIMD) by transthoracic echocardiography (TTE). (2) Methods: This was a retrospective cohort study using a prospective registry of septic shock at an Emergency Department from January 2011 and April 2017. All 1,776 consecutive adult septic shock patients treated with protocol-driven resuscitation bundle therapy and tested troponin-I were enrolled. SIMD was defined as left ventricular (LV) systolic/diastolic dysfunction, right ventricular (RV) diastolic dysfunction, or global/regional wall motion abnormalities (WMA). (3) Results: Of 660 (38.4%) septic shock patients with an elevated hs-TnI (≥0.04 ng/mL) at admission, 397 patients underwent TTE and 258 cases (65%) showed SIMD (LV systolic dysfunction (n = 163, 63.2%), LV diastolic dysfunction (n = 104, 40.3%), RV dysfunction (n = 97, 37.6%), and WMA (n = 186, 72.1%)). In multivariate analysis, peak hs-TnI (odds ratio 1.03, 95% confidence interval 1.01–1.06, p = 0.008) and ST-T wave changes in the electrocardiogram (odds ratio 1.82, 95% confidence interval 1.04–2.39, p = 0.013) were associated with SIMD, in contrast to hs-TnI level at admission. The area under the curve of peak hs-TnI was 0.668. When the peak hs-TnI cutoff value was 0.634 ng/mL, the sensitivity and specificity for SIMD were 58.6% and 59.1%, respectively. 4) Conclusions: About two-thirds of patients with an elevated hs-TnI level have various cardiac dysfunctions in terms of TTE. Rather than the initial level, the peak hs-TnI and ST-T change may be considered as a risk factor of SIMD.

Time course of liver nitric oxide concentration in early septic shock by cecal ligation and puncture in rats

Nitric Oxide ◽  
2010 ◽  
Vol 23 (3) ◽  
pp. 194-198 ◽  
Author(s):  
P. Eyenga ◽  
F. Lhuillier ◽  
J. Morel ◽  
D. Roussel ◽  
B. Sibille ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Septic Shock ◽  
Time Course ◽  
Cecal Ligation ◽  
Cecal Ligation And Puncture ◽  
Oxide Concentration ◽  
Nitric Oxide Concentration

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.

Sign in / Sign up

Export Citation Format

Share Document