Cardiopulmonary bypass increases endothelial dysfunction after pulmonary ischaemia-reperfusion in an animal model

Author(s):  
Jean Selim ◽  
Mouad Hamzaoui ◽  
Inès Boukhalfa ◽  
Zoubir Djerada ◽  
Laurence Chevalier ◽  
...  

Abstract OBJECTIVES Endothelial dysfunction during ischaemia-reperfusion (IR) is a major cause of primary graft dysfunction during lung transplantation. The routine use of cardiopulmonary bypass (CPB) during lung transplantation remains controversial. However, the contribution of CPB to pulmonary endothelial dysfunction remains unclear. The objective was to investigate the impact of CPB on endothelial dysfunction in a lung IR rat model. METHODS Rats were allocated to 4 groups: (i) Sham, (ii) IR, (iii) CPB and (iv) IR-CPB. The primary outcome was the study of pulmonary vascular reactivity by wire myograph. We also assessed glycocalyx degradation by enzyme-linked immunosorbent assay and electron microscopy and both systemic and pulmonary inflammation by enzyme-linked immunosorbent assay and immunohistochemistry. Rats were exposed to 45 min of CPB and IR. We used a CPB model allowing femoro-femoral support with left pulmonary hilum ischaemia for IR. RESULTS Pulmonary endothelium-dependent relaxation to acetylcholine was markedly reduced in the IR-CPB group (10.7 ± 9.1%) compared to the IR group (50.5 ± 5.2%, P < 0.001), the CPB group (54.1 ± 4.7%, P < 0.001) and the sham group (80.8 ± 6.7%, P < 0.001), suggesting that the association of pulmonary IR and CPB increases endothelial dysfunction. In IR-CPB, IR and CPB groups, vasorelaxation was completely abolished when inhibiting nitric oxide synthase, suggesting that this relaxation process was mainly mediated by nitric oxide. We observed higher syndecan-1 plasma levels in the IR-CPB group in comparison with the other groups, reflecting an increased degradation of glycocalyx. We also observed higher systemic inflammation in the IR-CPB group as shown by the increased plasma levels of IL-1β, IL-10. CONCLUSIONS CPB significantly increased the IR-mediated effects on pulmonary endothelial dysfunction. Therefore, the use of CPB during lung transplantation could be deleterious, by increasing endothelial dysfunction.

Perfusion ◽  
2021 ◽  
pp. 026765912110148
Author(s):  
Joseph Mc Loughlin ◽  
Lorraine Browne ◽  
John Hinchion

Objectives: Cardiac surgery using cardiopulmonary bypass frequently provokes a systemic inflammatory response syndrome. This can lead to the development of low cardiac output syndrome (LCOS). Both of these can affect morbidity and mortality. This study is a systematic review of the impact of gaseous nitric oxide (gNO), delivered via the cardiopulmonary bypass (CPB) circuit during cardiac surgery, on post-operative outcomes. It aims to summarise the evidence available, to assess the effectiveness of gNO via the CPB circuit on outcomes, and highlight areas of further research needed to develop this hypothesis. Methods: A comprehensive search of Pubmed, Embase, Web of Science and the Cochrane Library was performed in May 2020. Only randomised control trials (RCTs) were considered. Results: Three studies were identified with a total of 274 patients. There was variation in the outcomes measures used across the studies. These studies demonstrate there is evidence that this intervention may contribute towards cardioprotection. Significant reductions in cardiac troponin I (cTnI) levels and lower vasoactive inotrope scores were seen in intervention groups. A high degree of heterogeneity between the studies exists. Meta-analysis of the duration of mechanical ventilation, length of ICU stay and length of hospital stay showed no significant differences. Conclusion: This systematic review explored the findings of three pilot RCTs. Overall the hypothesis that NO delivered via the CPB circuit can provide cardioprotection has been supported by this study. There remains a significant gap in the evidence, further high-quality research is required in both the adult and paediatric populations.


2015 ◽  
Vol 34 (4) ◽  
pp. 300-307 ◽  
Author(s):  
Swati Omanwar ◽  
M. Fahim

Vascular endothelium plays a vital role in the organization and function of the blood vessel and maintains homeostasis of the circulatory system and normal arterial function. Functional disruption of the endothelium is recognized as the beginning event that triggers the development of consequent cardiovascular disease (CVD) including atherosclerosis and coronary heart disease. There is a growing data associating mercury exposure with endothelial dysfunction and higher risk of CVD. This review explores and evaluates the impact of mercury exposure on CVD and endothelial function, highlighting the interplay of nitric oxide and oxidative stress.


1996 ◽  
Vol 62 (6) ◽  
pp. 1639-1643 ◽  
Author(s):  
Lars Lindberg ◽  
Per Ola Kimblad ◽  
Trygve Sjöberg ◽  
Richard Ingemansson ◽  
Stig Steen

2020 ◽  
Vol 10 ◽  
pp. 204512532097379
Author(s):  
Wei Zheng ◽  
Yan-Ling Zhou ◽  
Cheng-Yu Wang ◽  
Xiao-Feng Lan ◽  
Bin Zhang ◽  
...  

Background: This study is the first to examine the association between plasma levels of brain-derived neurotrophic factor (BDNF) and the antisuicidal effects of repeated ketamine infusions in depressed patients with suicidal ideation. Methods: Fifty-seven depressed patients with suicidal ideation received six ketamine infusions (0.5 mg/kg) during a 12 days period. Suicidality was measured with the Scale for Suicidal Ideations (SSI-part 1), item 10 of the Montgomery–Åsberg Depression Rating Scale (MADRS), and item 3 of the Hamilton Depression Rating Scale (HAMD) at baseline, 1 day after the first infusion (1 day), 1 day after the sixth infusion (13 days), and at 2 weeks after the last infusion (26 days). Plasma levels of BDNF were measured by enzyme-linked immunosorbent assay at baseline, 13 days, and 26 days. Results: Overall, 46 (80.7%) depressed patients with suicidal ideation had an antisuicidal response at 13 days. Despite a significant reduction in suicidal symptoms over time, no changes in plasma levels of BDNF were found after ketamine treatment when compared with baseline. Correlation analysis showed that no significant association was observed between the plasma levels of BDNF and the changes in the severity of suicidal symptoms as measured by SSI-part 1, item 10 of the MADRS, or item 3 of the HAMD at 1 day, 13 days, and 26 days (all p < 0.05). Conclusion: Our results indicated that plasma levels of BDNF may not serve as a biomarker for determining the antisuicidal effects of six ketamine infusions in depressed patients with suicidal ideation.


2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Worlanyo Tashie ◽  
Linda Ahenkorah Fondjo ◽  
William K. B. A. Owiredu ◽  
Richard K. D. Ephraim ◽  
Listowell Asare ◽  
...  

Background. Preeclampsia is a major cause of maternal and neonatal morbidity and mortality in sub-Saharan Africa. Evidence indicates that endothelial dysfunction is central to the pathogenesis of preeclampsia. This study assessed the level of the components of the arginine-nitric oxide pathway to evaluate endothelial dysfunction in normotensive pregnancies and pregnancies complicated with preeclampsia. Methods. This case-control study was conducted among pregnant women who visited Comboni Hospital from January 2017 to May 2018. A total of 180 pregnant women comprising 88 preeclamptic women (PE) and 92 healthy normotensive pregnant women (NP) were recruited. Sociodemographic, clinical, and obstetric data were obtained using validated questionnaires. Blood pressure and anthropometrics were measured, and blood samples were collected for the estimation of nitric oxide (NO∙), L-arginine, asymmetric dimethylarginine (ADMA), and 3-nitrotyrosine using an enzyme-linked immunosorbent assay technique. Results. The mean NO∙ ( p = 0.010 ) and L-arginine/ADMA ratio ( p < 0.0001 ) was significantly lower in PE compared to NP while mean L-arginine ( p = 0.034 ), ADMA ( p < 0.0001 ), and 3-nitrotyrosine ( p < 0.0001 ) were significantly higher in PE than NP. ADMA showed a significant positive association with systolic blood pressure ( β = 0.454 , p = 0.036 ) in severe PE. Women with PE had significant intrauterine growth restriction ( p < 0.0001 ) and low birth weight infants ( p < 0.0001 ) when compared to NP. Conclusion. Preeclampsia is associated with reduced NO∙ bioavailability, L-arginine/ADMA ratio, and elevated levels of ADMA and 3-nitrotyrosine. Measurements of the levels of these parameters can help in the early prediction of endothelial dysfunction in preeclampsia. Exogenous therapeutic supplementation with L-arginine during pregnancy to increase the L-arginine/ADMA ratio should be considered to improve endothelial function in preeclampsia and pregnant women at risk of developing preeclampsia.


1984 ◽  
Vol 317 (6) ◽  
pp. 718-719 ◽  
Author(s):  
W. Müller-Esterl ◽  
A. Oettl ◽  
E. Truscheit ◽  
H. Fritz

BMJ Open ◽  
2019 ◽  
Vol 9 (8) ◽  
pp. e026664 ◽  
Author(s):  
Luregn J Schlapbach ◽  
Stephen Brian Horton ◽  
Debbie Amanda Long ◽  
John Beca ◽  
Simon Erickson ◽  
...  

IntroductionCongenital heart disease (CHD) is a major cause of infant mortality. Many infants with CHD require corrective surgery with most operations requiring cardiopulmonary bypass (CPB). CPB triggers a systemic inflammatory response which is associated with low cardiac output syndrome (LCOS), postoperative morbidity and mortality. Delivery of nitric oxide (NO) into CPB circuits can provide myocardial protection and reduce bypass-induced inflammation, leading to less LCOS and improved recovery. We hypothesised that using NO during CPB increases ventilator-free days (VFD) (the number of days patients spend alive and free from invasive mechanical ventilation up until day 28) compared with standard care. Here, we describe the NITRIC trial protocol.Methods and analysisThe NITRIC trial is a randomised, double-blind, controlled, parallel-group, two-sided superiority trial to be conducted in six paediatric cardiac surgical centres. One thousand three-hundred and twenty infants <2 years of age undergoing cardiac surgery with CPB will be randomly assigned to NO at 20 ppm administered into the CPB oxygenator for the duration of CPB or standard care (no NO) in a 1:1 ratio with stratification by age (<6 and ≥6 weeks), single ventricle physiology (Y/N) and study centre. The primary outcome will be VFD to day 28. Secondary outcomes include a composite of LCOS, need for extracorporeal membrane oxygenation or death within 28 days of surgery; length of stay in intensive care and in hospital; and, healthcare costs. Analyses will be conducted on an intention-to-treat basis. Preplanned secondary analyses will investigate the impact of NO on host inflammatory profiles postsurgery.Ethics and disseminationThe study has ethical approval (HREC/17/QRCH/43, dated 26 April 2017), is registered in the Australian New Zealand Clinical Trials Registry (ACTRN12617000821392) and commenced recruitment in July 2017. The primary manuscript will be submitted for publication in a peer-reviewed journal.Trial registration numberACTRN12617000821392


Author(s):  
S. I. Henyk ◽  
V. A. Gryb ◽  
L. T. Maksymchuk ◽  
O. O. Doroshenko ◽  
Ya. I. Henyk

Transient ischemic attack (TIA) in the vertebral-basilar system (VBS) is characterized by an acute onset of focal neurological symptoms due to short-term local ischemia of the brain. According to various authors, temporary neurological manifestations of circulatory insufficiency in VBS can progress to complete stroke within 2-5 years in 30-50% of patients, leading to disability of about 80% of patients. Its diagnosis is associated with some difficulties due to the variability of clinical manifestations, clinical similarity with other diseases and, as a consequence, incorrect therapeutic tactics. The aim of the study was to investigate changes of endothelial function in TIA in VBS by determining the levels of homocysteine (HC) and vascular endothelial growth factor (WEGF) at different stages of neurological deficiency (ND). 78 patients with TIA in VBS were examined. The questionnaire developed by us was used to determine the stage of ND in TIA. The level of HC was determined by enzyme-linked immunosorbent assay. WEGF was determined using the "sandwich" method of enzyme-linked immunosorbent assay. In the group of patients with stage I ND, a tendency to HC increase in 1.1 times was detected compared with almost healthy persons (AHP), stage II - HC increased in 1.5 times (p <0.05), and stage III - in 1.9 times (p <0.05). Also significant difference (1.8 times) was revealed at stage III compared to the index of stage I (p <0.05). WEGF at the 1st stage of ND significantly increased in 1,7 times in comparison with AHP (p <0.05), at the 2nd stage there was a tendency to increase (in 1.2 times), at the 3d stage there was a significant increase in WEGF in comparison with AHP (in 2.9 times) (p <0.05), and compared with indicators of I (in 1.8 times) (p <0.05) and II stages (2.6 times) (p <0 , 05). We have shown that TIA in VBS is accompanied by endothelial dysfunction (increase in HC and WEGF), which is more pronounced with aggravation of the ND. To evaluate the prognosis of the disease, we recommend using a questionnaire for determination the stage of ND in TIA in VBS and to identify markers of endothelial function such as HC and WEGF.


Author(s):  
Lúcia M. BRAGAZZA ◽  
Adelaide J. VAZ ◽  
Afonso D.C. PASSOS ◽  
Osvaldo M. TAKAYANAGUI ◽  
Paulo M. NAKAMURA ◽  
...  

Considering the impact of cysticercosis on public health, especially the neurologic form of the disease, neurocysticercosis (NC), we studied the frequency of positivity of anti-Taenia solium cysticercus antibodies in serum samples from 1,863 inhabitants of Cássia dos Coqueiros, SP, a municipal district located 80 km from Ribeirão Preto, an area considered endemic for cysticercosis. The 1,863 samples were tested by enzyme linked immunosorbent assay (ELISA) using an antigenic extract from Taenia crassiceps vesicular fluid (Tcra). The reactive and inconclusive ELISA samples were tested by immunoblotting. Of the 459 samples submitted to immunoblotting, 40 were strongly immunoreactive to the immunodominant 18 and 14 kD peptides. Considering the use of immunoblotting as confirmatory due to its high specificity, the anti-cysticercus serum prevalence in this population was 2.1%.


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