real-time-pressure-volume-analysis-acute-myocardial-infarction

Real-time Pressure-volume Analysis of Acute Myocardial Infarction in Mice

Acute myocardial infarction can lead to acute heart failure and cardiogenic shock. The evaluation of hemodynamics is critical for the evaluation of any ...

simultaneous-3d-analysis-cardiac-damage-immune-response-reperfused

Simultaneous 3D Analysis of Cardiac Damage and Immune Response in Reperfused Acute Myocardial Infarction Using Light Sheet Fluorescence Microscopy

Complex cellular interactions determine functional and structural tissue remodeling during reperfused acute myocardial infarction (repAMI). These ...

University Hospital Essen

Following successful resuscitation from cardiac arrest (CA), neurological impairment and other types of organ dysfunction cause significant morbidity and mortality-a condition termed post-cardiac arrest syndrome. Whole-body ischemia/reperfusion with oxygen debt activates immunologic and coagulation pathways increasing the risk of multiple organ failure and infection. We here examined the role of the pro-inflammatory cytokine macrophage migration inhibitory factor (MIF) in post-cardiac arrest syndrome.

MIF reflects tissue damage rather than inflammation in post-cardiac arrest syndrome in a real life cohort.

Macrophage migration inhibitory factor (MIF) is known to amplify the immune response in septic animal models. Few clinical data support this pro-inflammatory role in septic patients. Renal replacement therapy (RRT) as adjuvants in the complex therapy of sepsis has been proposed as a possible approach to eliminate elevated circulating cytokines. Since recent data suggest that MIF can be effectively removed from the circulating blood pool in patients with chronic kidney disease, we here aimed to investigate whether RRT in septic shock can lower plasma levels of this pro-inflammatory cytokine in septic shock patients.

Renal replacement therapy neutralizes elevated MIF levels in septic shock.

D-dopachrome tautomerase (MIF-2 or DDT) is a member of the macrophage migration inhibitory factor (MIF) superfamily and a close structural homolog to MIF. Circulating MIF-2 has been described to be elevated in patients suffering from sepsis, severe burn injury and after surgery. We sought to evaluate the prognostic value of MIF-2 in critically ill patients.

Elevated MIF-2 levels predict mortality in critically ill patients.

Macrophage migration inhibitory factor (MIF) is a pleiotropic inflammatory protein and contributes to several different inflammatory and ischemic/hypoxic diseases. MIF was shown to be cardioprotective in experimental myocardial ischemia/reperfusion injury and its expression is regulated by the transcription factor hypoxia-inducible factor (HIF)-1α. We here report on MIF expression in the failing human heart and assess myocardial MIF in different types of cardiomyopathy. Myocardial tissue samples from  = 30 patients were analyzed by quantitative Real-Time PCR. MIF and HIF-1α mRNA expression was analyzed in myocardial samples from patients with ischemic (ICM) and non-ischemic cardiomyopathy (NICM) and from patients after heart transplantation (HTX). MIF expression was elevated in myocardial samples from patients with ICM compared to NICM. Transplanted hearts showed lower MIF levels compared to hearts from patients with ICM. Expression of HIF-1α was analyzed and was shown to be significantly increased in ICM patients compared to patients with NICM. MIF and HIF-1α mRNA is expressed in the human heart. MIF and HIF-1α expression depends on the underlying type of cardiomyopathy. Patients with ICM show increased myocardial MIF and HIF-1α expression.

Myocardial Expression of Macrophage Migration Inhibitory Factor in Patients with Heart Failure.

Cardioprotection by salvage of the infarct-affected myocardium is an unmet yet highly desired therapeutic goal. To develop new dedicated therapies, experimental myocardial ischemia/reperfusion (I/R) injury would require methods to simultaneously characterize extent and localization of the damage and the ensuing inflammatory responses in whole hearts over time. Here we present a three-dimensional (3D), simultaneous quantitative investigation of key I/R injury-components by combining bleaching-augmented solvent-based non-toxic clearing (BALANCE) using ethyl cinnamate (ECi) with light sheet fluorescence microscopy. This allows structural analyses of fluorescence-labeled I/R hearts with exceptional detail. We discover and 3D-quantify distinguishable acute and late vascular I/R damage zones. These contain highly localized and spatially structured neutrophil infiltrates that are modulated upon cardiac healing. Our model demonstrates that these characteristic I/R injury patterns can detect the extent of damage even days after the ischemic index event hence allowing the investigation of long-term recovery and remodeling processes.

Contemporaneous 3D characterization of acute and chronic myocardial I/R injury and response.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Publisher Correction: Contemporaneous 3D characterization of acute and chronic myocardial I/R injury and response.

Cancer survival rates have increased significantly because of improvements in therapy regimes and novel immunomodulatory drugs. Recently, combination therapies of anthracyclines and immune checkpoint inhibitors (ICIs) have been proposed to maximize neoplastic cell removal. However, it has been speculated that a priori anthracycline exposure may prone the heart vulnerable to increased toxicity from subsequent ICI therapy, such as an anti-programmed cell death protein 1 (PD1) inhibitor. Here, we used a high-dose anthracycline mouse model to characterize the role of the PD1 immune checkpoint signaling pathway in cardiac tissue using flow cytometry and immunostaining. Anthracycline treatment led to decreased heart function, increased concentration of markers of cell death after six days and a change in heart cell population composition with fewer cardiomyocytes. At the same time point, the number of PD1 ligand (PDL1)-positive immune cells and endothelial cells in the heart decreased significantly. The results suggest that PD1/PDL1 signaling is affected after anthracycline treatment, which may contribute to an increased susceptibility to immune-related adverse events of subsequent anti-PD1/PDL1 cancer therapy.

Anthracycline Therapy Modifies Immune Checkpoint Signaling in the Heart.

CD47 is a cell surface protein controlling phagocytotic activity of innate immune cells. CD47 blockade was investigated as an immune checkpoint therapy in cancer treatment, enhancing phagocytosis of tumor cells by macrophages. Anti-CD47 treatment also reduced injury size during reperfused acute myocardial infarction (repAMI) by enhancing phagocytotic acitivity of macrophages. Little is known about the impact of CD47 blockade on neutrophils, representing the main portion of early infiltrating immune cells after repAMI. Therefore, we performed 45 min of cardiac ischemia followed by 24 h of reperfusion, observing a decreased cardiac injury size measured by triphenyl tetrazolium chloride (TTC) Evan's blue staining. We were able to detect this effect with an innovative three-dimensional method based on light sheet fluorescence microscopy (LSFM). This further allowed us a simultaneous analysis of neutrophil infiltration, showing an unaltered amount of injury-associated neutrophils with reduced cardiac injury volume from repAMI. This observation suggests modulated phagocytosis of cell debris by neutrophils. Therefore, we performed flow cytometry analysis, revealing an increased phagocytotic activity of neutrophils . These findings highlight that CD47 blockade also enhances phagocytosis of cardiac cell debris by neutrophils, which might be an additional protective effect of anti-CD47 treatment after repAMI.

ArticleTotal : 2	Year
Publication title Cited by 2	2018
Publication title	2025

Article	Year
MIF reflects tissue damage rather than inflammation in post-cardiac arrest syndrome in a real life cohort. Resuscitation\| PubMed ID: 26784134	2016
Renal replacement therapy neutralizes elevated MIF levels in septic shock. Journal of intensive care\| PubMed ID: 27313864	2016
Elevated MIF-2 levels predict mortality in critically ill patients. Journal of critical care\| PubMed ID: 28329734	2017
Myocardial Expression of Macrophage Migration Inhibitory Factor in Patients with Heart Failure. Journal of clinical medicine\| PubMed ID: 29027966	2017
Contemporaneous 3D characterization of acute and chronic myocardial I/R injury and response. Nature communications\| PubMed ID: 31127113	2019
Publisher Correction: Contemporaneous 3D characterization of acute and chronic myocardial I/R injury and response. Nature communications\| PubMed ID: 31217436	2019
Anthracycline Therapy Modifies Immune Checkpoint Signaling in the Heart. International journal of molecular sciences\| PubMed ID: 37047026	2023
CD47 blockade enhances phagocytosis of cardiac cell debris by neutrophils. International journal of cardiology. Heart & vasculature\| PubMed ID: 37731517	2023

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