The Inflammatory Response in Cardiac Surgery. An Up-to-date Overview with the Emphasis on the Role of Heat Shock Proteins (HSPs) 60 and 70

Kuneš, P; Lonský,; Mandak, Jiri; Brtko, Miroslav; Koláčková, Martina; Andrýs, Ctirad; Kudlová, Manuela; Krejsek, Jan

doi:10.14712/18059694.2017.62

Cited by 8 publications

(7 citation statements)

References 36 publications

(31 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our results demonstrate that renal IRI leads to an increase in mtDNA and the pro-inflammatory cytokine IL-6. IL-6 may in turn activate intracellular signaling and stimulate leukocyte-endothelial interaction leading to leukocyte migration and tissue damage [28].…”

Section: Discussionmentioning

confidence: 99%

Toll-like receptor 9 and the inflammatory response to surgical trauma and cardiopulmonary bypass

Naase

Harling

Kidher

et al. 2020

J Cardiothorac Surg

View full text Add to dashboard Cite

Objectives: Cardiac surgery can lead to post-operative end-organ complications secondary to activation of systemic inflammatory response. We hypothesize that surgical trauma or cardiopulmonary bypass (CPB) may initiate systemic inflammatory response via release of mitochondrial DNA (mtDNA) signaling Toll-like receptor 9 (TLR9) and interleukin-6 production (IL-6). Materials and methods: The role of TLR9 in systemic inflammatory response in cardiac surgery was studied using a murine model of sternotomy and a porcine model of sternotomy and CPB. mtDNA and IL-6 were measured with and without TLR9-antagonist treatment. To study ischemia-reperfusion injury, we utilized an ex-vivo porcine kidney model. Results: In the rodent model (n = 15), circulating mtDNA increased 19-fold (19.29 ± 3.31, p < 0.001) and plasma IL-6 levels increased 59-fold (59.06 ± 14.98) at 1-min post-sternotomy compared to pre-sternotomy. In the murine model (n = 11), administration of TLR-9 antagonists lowered IL-6 expression post-sternotomy when compared to controls (59.06 ± 14.98 vs. 5.25 ± 1.08) indicating that TLR-9 is a positive regulator of IL-6 after sternotomy. Using porcine models (n = 10), a significant increase in circulating mtDNA was observed after CPB (Fold change 29.9 ± 4.8, p = 0.005) and along with IL-6 following renal ischaemia-reperfusion. Addition of the antioxidant sulforaphane reduced circulating mtDNA when compared to controls (FC 7.36 ± 0.61 vs. 32.0 ± 4.17 at 60 min post-CPB). Conclusion: CPB, surgical trauma and ischemic perfusion injury trigger the release of circulating mtDNA that activates TLR-9, in turn stimulating a release of IL-6. Therefore, TLR-9 antagonists may attenuate this response and may provide a future therapeutic target whereby the systemic inflammatory response to cardiac surgery may be manipulated to improve clinical outcomes.

show abstract

Section: Discussionmentioning

confidence: 99%

Toll-like receptor 9 and the inflammatory response to surgical trauma and cardiopulmonary bypass

Naase

Harling

Kidher

et al. 2020

J Cardiothorac Surg

View full text Add to dashboard Cite

show abstract

“…Apoptosis Rate multiple organ dysfunction [6,7] . Furthermore, abrupt reperfusion of occluded myocardial vessels can extend hypoxic damage in the heart caused by Ischemia/Reperfusion Injury (IRI) [8] .…”

Section: Exploring the Pleiotropic Effects Of Levosimendan -Impact Onmentioning

confidence: 99%

CARDIAC-Exploring the Pleiotropic Effects of Levosimendan – Impact on Systemic Inflammatory Parameters and Molecular Salvage Path-ways by Modulation of Cytokine Levels and Tissue Apoptosis Rate

Boeken¹,

Immohr²,

Jenke³

et al. 2017

JHC

View full text Add to dashboard Cite

Introduction: Although levosimendan is commonly used, recent clinical trials remain ambiguous. Extra-corporeal circulation induces Ischemia/Reperfusion Injury (IRI) and inflammation. Methods: In our study, male rats (400-500 g) were cannulated, intravenously treated with 12 µg/kg body weight levosimendan (n = 4) or vehicle solution (n = 5) and connected to a heart-lung machine. To induce IRI, 45 min circulatory arrest was performed. After reperfusion, rats were euthanized. Cytokines were analyzed by ELISA and salvage pathways and apoptosis by western blot. Results: After circulatory arrest, heart rate and blood pressure recovered faster in the levosimendan group. The need for buffering solution and catecholamines was 40% lower in the levosimendan group. Cytokines increased in both groups during the procedure but levosimendan diminished the increase of IL-6(-44 %). Whereas activation of AKT did not differ between groups, p44-42 MAPK (+ 29%) and p38 MAPK (+ 17%) increased and STAT3 (-55%) decreased in levosimendan heart samples. PARP-cleavage was 35% decreased in the levosimendan group indicating lower apoptosis. Conclusions: Application of levosimendan seems to affect salvage pathways, cytokines and apoptosis. Levosimendan treated rats recovered faster and showed beneficial changes. These findings may serve our understanding of levosimendan in the context of IRI, allowing better patient tailored drug application.

show abstract

“…The exposure of the blood to artificial surfaces activates a variety of signalling cascades which induce an inflammatory response, first described as whole body inflammation syndrome [ 1 ]. Evolutionary needed for wound healing, under unfavourable haemodynamic conditions as it can occur during CPB, this may lead in 2-10% of all cases to a systemic inflammatory response syndrome (SIRS), which may further aggravate to multiple organ dysfunction syndrome (MODS) [ 2 ],[ 3 ]. SIRS is mediated primarily by the cells of the innate immune system.…”

Section: Introductionmentioning

confidence: 99%

“…They mediate key signalling events following I/R and the extent of their induction/activation determines the outcome of tissue adaption and inflammation after CPB and DHCA [ 10 ],[ 18 ],[ 19 ]. MAPK, STAT3, HO-1 and HSP70 are mediators of the I/R- and cytokine-induced organ damage and also potential targets for selective inhibitors or activators which may supress SIRS [ 2 ],[ 19 ]-[ 21 ]. Therefore we considered it as our primary goal to determine the organ-specific signalling status in target organs possibly affected by MODS.…”

Section: Introductionmentioning

confidence: 99%

A cardiopulmonary bypass with deep hypothermic circulatory arrest rat model for the investigation of the systemic inflammation response and induced organ damage

et al. 2014

View full text Add to dashboard Cite

BackgroundCardiopulmonary bypass (CPB) is a commonly used technique in cardiac surgery. CPB is however associated with a strong induction of systemic inflammatory response syndrome (SIRS) which in conjunction with ischemia and reperfusion may lead to multiple organ failure.The aim of the study was to establish and characterize a CPB rat model incorporating deep hypothermic circulatory arrest with a specific focus on the extent of the inflammatory reactions and organ damage as a groundwork for novel therapeutics against SIRS and I/R induced organ injury.Materials and methodsMale Wistar rats (n = 6) were cannulated for CPB, connected to a heart-lung-machine (HLM) and cooled to a temperature of 16°C before they underwent 45 minutes of deep hypothermic circulatory arrest with global ischaemia. Arrest was followed by rewarming and 60 minutes of reperfusion. Haemodynamic and vital parameters were recorded throughout the CPB procedure. Only animals displaying sinus rhythm throughout reperfusion were utilized for analysis. Rats were euthanized and tissue samples were harvested. Blood gas analysis was performed and blood samples were taken. Induction of organ damage was examined by analysis of protein levels and phosphorylation status of kinases and stress proteins. Results were compared to animals (n = 6) which did not undergo CPB.ResultsCPB induced leucocytosis and an increase of interleukin-6 and TNF-α plasma values indicating an inflammatory response. Markers of tissue damage and dysfunction, such as troponin T, creatinine and AST were elevated. Phosphorylation of STAT3 was induced in all examined organs. Activation of MAPK and induction of heat shock proteins occurred in an organ-specific manner with most pronounced effects in heart, lungs and kidneys.ConclusionsThe presented CPB rat model shows the induction of SIRS and activation of specific signalling cascades. SIRS seems not to be provoked during DHCA and is elicited mainly during reperfusion. This model might be suitable to test the efficacy of therapeutics applied in major heart surgery with and without DHCA.

show abstract

The Inflammatory Response in Cardiac Surgery. An Up-to-date Overview with the Emphasis on the Role of Heat Shock Proteins (HSPs) 60 and 70

Cited by 8 publications

References 36 publications

Toll-like receptor 9 and the inflammatory response to surgical trauma and cardiopulmonary bypass

Toll-like receptor 9 and the inflammatory response to surgical trauma and cardiopulmonary bypass

CARDIAC-Exploring the Pleiotropic Effects of Levosimendan – Impact on Systemic Inflammatory Parameters and Molecular Salvage Path-ways by Modulation of Cytokine Levels and Tissue Apoptosis Rate

A cardiopulmonary bypass with deep hypothermic circulatory arrest rat model for the investigation of the systemic inflammation response and induced organ damage

Contact Info

Product

Resources

About