Roles of inflammation and apoptosis in experimental brain death–induced right ventricular failure

Belhaj, Asmae; Dewachter, Laurence; Rorive, Sandrine; Remmelink, Myriam; Weynand, Birgit; Mélot, Christian; Galanti, Laurence; Hupkens, Emeline; Sprockeels, Thomas; Dewachter, Céline; Créteur, Jacques; McEntee, Kathleen; Naeije, Robert; Rondelet, Benoît

doi:10.1016/j.healun.2016.05.014

Cited by 12 publications

(33 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…RV failure induced by transient pulmonary artery banding was associated with a RV increase in TNF-α expression, whereas circulating serum levels of TNF-α remained undetectable after pulmonary artery banding (Dewachter et al, 2010 ), suggesting local early expression of this pro-inflammatory cytokine in this experimental model. A local increased expression of TNF-α was also observed in experimental brain death-induced RV dysfunction (Belhaj et al, 2016 ) and tightly correlated to the prediction to develop RV failure early after heart transplantation (Birks et al, 2000 ). Expression of TNF-α was increased in the failing RV after 6-month systemic-to-pulmonary shunting in pigs, together with increased circulating serum TNF-α levels (Rondelet et al, 2012 ).…”

Section: Mediators and Effectors Of Inflammation—cytokines And Chemokmentioning

confidence: 87%

“…This was associated to increased RV expression of cytokines and chemokines, together with RV infiltration of neutrophils and macrophages, indicating an early immune response. RV dysfunction associated to brain death was also associated to increased expression of ICAM-1,-2, and VCAM-1 in the RV (Stoica et al, 2005 ; Belhaj et al, 2016 ), suggesting endothelial activation, which persists in the post-operative period, even in the absence of acute rejection. On the other hand, we also know that cytokines induce the apoptosis of cardiac endothelial cells and increase endothelial generation of reactive oxygen species (ROS), which induce the production of plasminogen activator inhibition-1 and of collagen by cardiac endothelial cells (Chandrasekar et al, 2004 ).…”

Section: Inflammatory and Immune Cellsmentioning

confidence: 99%

See 1 more Smart Citation

Inflammation in Right Ventricular Failure: Does It Matter?

Dewachter

2018

Front. Physiol.

Self Cite

View full text Add to dashboard Cite

Right ventricular (RV) failure is a common consequence of acute and chronic RV overload of pressure, such as after pulmonary embolism and pulmonary hypertension. It has been recently realized that symptomatology and survival of patients with pulmonary hypertension are essentially determined by RV function adaptation to increased afterload. Therefore, improvement of RV function and reversal of RV failure are treatment goals. Currently, the pathophysiology and the pathobiology underlying RV failure remain largely unknown. A better understanding of the pathophysiological processes involved in RV failure is needed, as there is no proven treatment for this disease at the moment. The present review aims to summarize the current understanding of the pathogenesis of RV failure, focusing on inflammation. We attempt to formally emphasize the importance of inflammation and associated representative inflammatory molecules and cells in the primum movens and development of RV failure in humans and in experimental models. We present inflammatory biomarkers and immune mediators involved in RV failure. We focus on inflammatory mediators and cells which seem to correlate with the deterioration of RV function and also explain how all these inflammatory mediators and cells might impact RV function adaptation to increased afterload. Finally, we also discuss the evidence on potential beneficial effects of targeted anti-inflammatory agents in the setting of acute and chronic RV failure.

show abstract

Section: Mediators and Effectors Of Inflammation—cytokines And Chemokmentioning

confidence: 87%

Section: Inflammatory and Immune Cellsmentioning

confidence: 99%

Inflammation in Right Ventricular Failure: Does It Matter?

Dewachter

2018

Front. Physiol.

Self Cite

View full text Add to dashboard Cite

show abstract

“…Immunohistochemistry were performed as previously described [ 10 ]. After progressive rehydration, 5μm-sections of lung tissue fixed and embedded in paraffin were incubated in target retrieval buffer (Dako, Glostrup, Denmark) and heated in a bath for 20 minutes at 95°C for target retrieval.…”

Section: Methodsmentioning

confidence: 99%

“…We therefore investigated the biology and the pathophysiology of lung injury in a pig model of brain death [ 10 ]. Pulmonary capillary pressure (PCP) as a determinant of hydrostatic lung edema was determined from the analysis of pressure decay curves after single pulmonary arterial occlusion [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

Mechanical versus humoral determinants of brain death-induced lung injury

et al. 2017

Self Cite

View full text Add to dashboard Cite

BackgroundThe mechanisms of brain death (BD)-induced lung injury remain incompletely understood, as uncertainties persist about time-course and relative importance of mechanical and humoral perturbations.MethodsBrain death was induced by slow intracranial blood infusion in anesthetized pigs after randomization to placebo (n = 11) or to methylprednisolone (n = 8) to inhibit the expression of pro-inflammatory mediators. Pulmonary artery pressure (PAP), wedged PAP (PAWP), pulmonary vascular resistance (PVR) and effective pulmonary capillary pressure (PCP) were measured 1 and 5 hours after Cushing reflex. Lung tissue was sampled to determine gene expressions of cytokines and oxidative stress molecules, and pathologically score lung injury.ResultsIntracranial hypertension caused a transient increase in blood pressure followed, after brain death was diagnosed, by persistent increases in PAP, PCP and the venous component of PVR, while PAWP did not change. Arterial PO2/fraction of inspired O2 (PaO2/FiO2) decreased. Brain death was associated with an accumulation of neutrophils and an increased apoptotic rate in lung tissue together with increased pro-inflammatory interleukin (IL)-6/IL-10 ratio and increased heme oxygenase(HO)-1 and hypoxia inducible factor(HIF)-1 alpha expression. Blood expressions of IL-6 and IL-1β were also increased. Methylprednisolone pre-treatment was associated with a blunting of increased PCP and PVR venous component, which returned to baseline 5 hours after BD, and partially corrected lung tissue biological perturbations. PaO2/FiO2 was inversely correlated to PCP and lung injury score.ConclusionsBrain death-induced lung injury may be best explained by an initial excessive increase in pulmonary capillary pressure with increased pulmonary venous resistance, and was associated with lung activation of inflammatory apoptotic processes which were partially prevented by methylprednisolone.

show abstract

“…Adrie et al 40 , demonstraram em pacientes com ME um aumento da expressão de proteínas pro-apoptóticas e elevação de citocinas inflamatórias. Belhaj et al 105 verificaram que a metilpredinisona reduz, mas não abole, a reação inflamatória e a apoptose produzida pela ME. Os resultados encontrados nesse trabalho mostraram que a SH provoca melhora do padrão inflamatório de animais submetidos à ME, com redução significativa da expressão de moléculas de adesão leucocitária, fator de necrose tumoral alfa e aumento de proteínas anti-apoptóticas.…”

unclassified

Estudo dos efeitos da solução salina hipertônica sobre a função e alterações do tecido cardíaco em modelo de morte encefálica em ratos

Magalhães¹

View full text Add to dashboard Cite

Roles of inflammation and apoptosis in experimental brain death–induced right ventricular failure

Cited by 12 publications

References 47 publications

Inflammation in Right Ventricular Failure: Does It Matter?

Inflammation in Right Ventricular Failure: Does It Matter?

Mechanical versus humoral determinants of brain death-induced lung injury

Estudo dos efeitos da solução salina hipertônica sobre a função e alterações do tecido cardíaco em modelo de morte encefálica em ratos

Contact Info

Product

Resources

About