Induction of inflammatory mediators during reperfusion of the human heart

Valen, Guro; Paulsson, Gabrielle; Vaage, Jarle

doi:10.1016/s0003-4975(00)02146-9

Cited by 59 publications

(36 citation statements)

References 20 publications

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“…It has been reported that CPB induces the activation of NF-jB by myocardial ischaemia and reperfusion [32]. However, a recent study showed that NFjB activity in cardiomyocytes and coronary endothelium was unchanged at the end of CPB [33].…”

Section: Discussionmentioning

confidence: 93%

The effects of dexmedetomidine on inflammatory mediators after cardiopulmonary bypass

et al. 2014

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SummaryCardiac surgery with cardiopulmonary bypass is associated with the development of a systemic inflammatory response that can often lead to dysfunction of major organs. We hypothesised that the highly selective a 2 -adrenergic agonist, dexmedetomidine, attenuates the systemic inflammatory response. Forty-two patients were randomly assigned to receive dexmedetomidine or saline after aortic cross-clamping). The mean (SD) levels of the nuclear protein plasma high-mobility group box 1 increased significantly from 5.1 (2.2) ng.ml À1 during (16.6 (7.3) ng.ml À1) and after (14.3 (8.2) ng.ml À1 ) cardiopulmonary bypass in the saline group. In the dexmedetomidine group, the levels increased significantly only during cardiopulmonary bypass (4.0 (1.9) ng.ml À1 baseline vs 10.8 (2.7) ng.ml À1 ) but not after (7.4 (3.8) ng.ml À1). Dexmedetomidine infusion also suppressed the rise in mean (SD) interleukin-6 levels after cardiopulmonary bypass (a rise of 124.5 (72.0) pg.ml À1 vs 65.3 (30.9) pg.ml À1 ). These suppressive effects of dexmedetomidine might be due to the inhibition of nuclear factor kappa B activation and suggest that intra-operative dexmedetomidine may beneficially inhibit inflammatory responses associated with ischaemia-reperfusion injury during cardiopulmonary bypass.

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Section: Discussionmentioning

confidence: 93%

The effects of dexmedetomidine on inflammatory mediators after cardiopulmonary bypass

et al. 2014

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“…NF-κB can rapidly activate the expression of genes involved in the inflammatory response, such as proinflammatory cytokines and adhesion molecules (20,21). The activation of NF-κB was observed during I/ R (22,23) and is considered to contribute to the occurrence and development of myocardial infarction (24,25). In most cells, NF-κB is present in the cytoplasm binding with an inhibitory protein called IκB.…”

Section: Discussionmentioning

confidence: 99%

Comparison of the Protective Effect of N-Acetylcysteine by Different Treatments on Rat Myocardial Ischemia-Reperfusion Injury

et al. 2008

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Abstract. Reactive oxygen species have been known as important contributors to ischemia / reperfusion (I / R) injury. Studies on the beneficial effect of N-acetylcysteine (NAC), a potent antioxidant, on limiting infarct size induced by I / R yielded contrasting results. The present study was undertaken to compare the effect of NAC by different administration methods on infarct size in a rat myocardial I/ R model. Rats underwent 30 min of left coronary occlusion followed by 4 h of reperfusion. Treatment with continuous infusion of NAC (150 mg / kg per hour) from 30 min before occlusion for 2 h (until 1 h after the start of reperfusion) produced a significant limitation of the infarct size as a percentage of the ischemic area (8%) compared to the non-treated control (60%). However, bolus injection of 150 mg / kg at 30 min prior to occlusion and 5 min prior to reperfusion failed to reduce it (56%) although the total dose is the same. The decreased total glutathione content and glutathione peroxidase activity in the ischemic region were recovered in the continuous infusion group, but not in the bolus injection group. The increased myeloperoxidase activity and phosphorylation of inhibitor κB after I / R were inhibited by the continuous treatment. These results indicate that the protective effect of NAC on myocardial infarction induced by I / R was different depending on the administration method. It is necessary to maintain blood concentration during the early period of reperfusion to obtain the beneficial effect of NAC.

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“…The expression of HLA-DR molecules on the inflammatory and endothelial cells as well as the overexpression of IFN-␥ genes provide evidence of an immunomediated reaction, 22 thus confirming our previous study. 8 The possibility that both cardiac RAS activation and coronary microvessel inflammation may be a reaction to myocardial necrosis, 23 surgery, 24 or ischemia should be considered. Myocardial necrosis or surgery may be reasonably excluded as causes of RAS activation and microvessel inflammation because the enrolled UA patients were troponinnegative, and myocardial biopsies were performed before extracorporeal circulation.…”

Section: Cardiac Ras Activation and Myocardial Ischemiamentioning

confidence: 99%

Cardiac Angiotensin II Participates in Coronary Microvessel Inflammation of Unstable Angina and Strengthens the Immunomediated Component

Serneri

Boddi

Modesti

et al. 2004

Circulation Research

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Abstract-Angiotensin (Ang) II is now recognized to be a mediator of a wide variety of inflammatory processes. This study investigated renin-angiotensin system (RAS) components and a number of inflammatory mediators in left ventricular biopsies from 2-vessel disease unstable angina (UA) (nϭ43) and stable angina (SA) (nϭ15) patients undergoing coronary bypass surgery. Biopsy samples from 6 patients undergoing valve replacement for mitral stenosis served as controls. UA patients were randomly assigned to angiotensin-converting enzyme (ACE)-inhibitor (ramipril), AT1 antagonist (valsartan), or placebo and treated during the 5 days preceding coronary bypass surgery, performed from 6 to 9 days after coronary angiography. During coronary angiography coronary blood flow was measured and samples were obtained from aorta and coronary sinus for determination of Ang I and Ang II gradients. The hearts of UA patients produced Ang II in a greater amount than in SA patients (PϽ0.01). UA biopsy samples showed numerous DR ϩ cells, identified as lymphocytes, macrophages, and endothelial cells. Reverse-transcriptase polymerase chain reaction showed overexpression of AGTN, ACE, and AT1-R genes, as well as upregulation of TNF-␣, IL-6, IFN-␥, and iNOS genes (PϽ0.01), with no differences between nonischemic and potentially ischemic areas. AGTN, ACE, and cytokine genes were mainly localized on endothelial cells. Ramipril and valsartan markedly decreased the expression levels of TNF-␣, IL-6, and iNOS, and, to a lesser extent, of IFN-␥ genes, but did not affect the number of DR ϩ cells, with no significant difference between the 2 treatments. These results show that locally generated Ang II amplifies the immunomediated inflammatory process of coronary microvessels occurring in unstable angina. Key words: angiotensin II Ⅲ unstable angina Ⅲ myocardial inflammation U nstable angina (UA) classes IIB and IIIB of Braunwald classification 1 are an acute manifestation thought to be caused by recent inflammatory activation within coronary atherosclerotic plaque, often resulting in the plaque erosion or rupture with consequent nonocclusive thrombus development. 2 Unstable or vulnerable plaques are characterized by increased accumulation of inflammatory cells, particularly macrophages and T-lymphocytes, and by a large lipid core and a thin fibrous cap. 3 A high number of inflammatory cells express DR molecules and IL-2 receptors, 4,5 thus indicating that antigen presentation, as well as an immunological reaction, occurred. 6 However, the concept that UA is only an intraplaque event is strongly restrictive because recent studies have shown that Ͼ1 coronary plaque is activated in acute coronary syndromes. 7 Moreover, we showed that also coronary microvessels are involved in UA by an acute inflammatory process with cellular and molecular characteristics of an immunomediated reaction. 8 The complex pathophysiology of UA is also suggested by the link that seems to exist between renin-angiotensin system (RAS) and atherosclerosis. 9 Several immunohisto...

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Induction of inflammatory mediators during reperfusion of the human heart

Cited by 59 publications

References 20 publications

The effects of dexmedetomidine on inflammatory mediators after cardiopulmonary bypass

The effects of dexmedetomidine on inflammatory mediators after cardiopulmonary bypass

Comparison of the Protective Effect of N-Acetylcysteine by Different Treatments on Rat Myocardial Ischemia-Reperfusion Injury

Cardiac Angiotensin II Participates in Coronary Microvessel Inflammation of Unstable Angina and Strengthens the Immunomediated Component

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