Histopathologic, Immunohistochemical Features and Profile of Viral Antigens in Patients with Myocarditis

We studied medical records and endomyocardial biopsies of patients with morphological confirmed lymphocytic myocarditis. The patients were divided into two groups: 1 - patients with arrhythmias; group 2 - patients with predominance syndrome heart failure. Morphological verification of myocarditis was based on World Heart Federation Consensus definition of Inflammatory Cardiomyopathy, 1997. Immunohistological study was performed to identify antigens of cardiotrophic viruses. We revealed some features in topic and character of morphological changes in depending on clinical scenario of myocarditis. In patients with chronic heart failure due to myocarditis revealed a high incidence of expression of LMP-antigen Epstein-Barr virus, the lack of expression of adenovirus antigens. Arrhythmic presentation of myocarditis was characterized by a high frequency of expression of enteroviral VP-1 antigen and the type 1 antigen herpes virus. We were not detected expression of the VP-2 antigen parvovirus B19. As a result the most severe inflammatory changes and interstitial fibrosis of intraventricular septum, widespread damage of myocytes the severe myocardial remodeling was found in patients with presentation of myocarditis by chronic heart failure. Interstitial fibrosis of the outflow tracts of the right ventricle, the low activity of inflammation and mild fibrotic changes were feature of arrhythmic scenario of myocarditis.</jats:p

The role of viruses, inflammation and myocardial macrophages in the development of idiopathic arrhythmia

We studied viral antigens, inflammation, and macrophages in the endomyocardial biopsies of patients with idiopathic arrhythmias. Immunohistological study was performed to identify the antigens of cardiotropic viruses and the types of lymphocytes and macrophages. We observed the presence of viral antigens in the myocardium of patients with and without histological criteria of myocarditis. Heart failure and ventricular arrhythmias were associated with small focal infiltration of the myocardium with macrophages. The presence of viral antigens in the myocardium was associated with fewer number of myocardial M2 macrophages. Severity of myocardial interstitial fibrosis correlated with small-focal infiltration of M2 macrophages

Macrophage activation and polarization in post-infarction cardiac remodeling

Adverse cardiac remodeling leads to impaired ventricular function and heart failure, remaining a major cause of mortality and morbidity in patients with acute myocardial infarction. It have been shown that, even if all the recommended therapies for ST-segment elevation myocardial infarction are performed, one third of patients undergoes progressive cardiac remodeling that represents morphological basis for following heart failure. The need to extend our knowledge about factors leading to different clinical scenarios of myocardial infarction and following complications has resulted in a research of immuno-inflammatory pathways and molecular activities as the basis for post-infarction remodeling. Recently, macrophages (cells of the innate immune system) have become a subject of scientific interest under both normal and pathological conditions. Macrophages, besides their role in host protection and tissue homeostasis, play an important role in pathophysiological processes induced by myocardial infarction. In this article we summarize data about the function of monocytes and macrophages plasticity in myocardial infarction and outline potential role of these cells as effective targets to control processes of inflammation, cardiac remodeling and healing following acute coronary event

Use of autoleukocyte, labelled with 99mTc-exametazine for evaluation of inglammatory changes in myocardium

Our purpose was to study the possibilities of autoleukocyte, labelled in vitro with 99mTc-exametazine (99m Tc-HMPAO), in evaluation of inflammatory changes of myocardium at patients with persistent form of atrial fibrillation (AF).We examined 30 patients with idiopathic persistent form of AF. For identification of the inflammatory areas in a myocardium before ablation scintigraphy (SPECT) 99mTc-HMPAO – leucocytes was carried out. Upon completion of scanning a perfusion scintigraphy of a myocardium with a 99mTc-methoxyisobutyl isonitrile (99mTc-MIBI) («Tehnetril» 99mTc, JSC Diamed, Russia) in rest under the standard protocol was carried out. Pathologic accumulation of 99mTc-HMPAO-leukocytes in a myocardium was revealed at 6 (20%) of the examined patients. Sensitivity of SPECT with 99mTc-HMPAO-leukocytes in diagnostics of inflammatory changes of a myocardium, according to our data, was - 80%, specificity - 92%, diagnostic accuracy - 90%

Use of autoleukocyte, labelled with 99mTc-exametazine for evaluation of inglammatory changes in myocardium

Our purpose was to study the possibilities of autoleukocyte, labelled in vitro with 99mTc-exametazine (99m Tc-HMPAO), in evaluation of inflammatory changes of myocardium at patients with persistent form of atrial fibrillation (AF).We examined 30 patients with idiopathic persistent form of AF. For identification of the inflammatory areas in a myocardium before ablation scintigraphy (SPECT) 99mTc-HMPAO – leucocytes was carried out. Upon completion of scanning a perfusion scintigraphy of a myocardium with a 99mTc-methoxyisobutyl isonitrile (99mTc-MIBI) («Tehnetril» 99mTc, JSC Diamed, Russia) in rest under the standard protocol was carried out. Pathologic accumulation of 99mTc-HMPAO-leukocytes in a myocardium was revealed at 6 (20%) of the examined patients. Sensitivity of SPECT with 99mTc-HMPAO-leukocytes in diagnostics of inflammatory changes of a myocardium, according to our data, was - 80%, specificity - 92%, diagnostic accuracy - 90%

Cardiac macrophages in wound healing following myocardial infarction: from experiment to clinic

Introduction: Macrophages are key innate immune cells that play a significant role in transition from inflammatory to regenerative phase during wound healing following myocardial infarction (MI). Despite the progress of experimental studies devoted to the innate immune response following MI, there is no significant advancement in clinical studies. Purpose: The purpose of the research was to translate experimental knowledge regarding macrophage subsets and their biomarkers in post infarction left ventricular remodeling and myocardial regeneration into results observed in clinical settings. We suggested protocol based on usage of macrophage biomarkers to study cellular basis of cardiac remodeling and healing in patients with MI. Methods: The study included 41 patients with fatal MI type 1. All patients were divided into 4 groups depending on the timeline of MI histopathology. In addition to routine histopathological analysis macrophages infiltration was assessed by immunohistochemistry. We used CD68 as a marker for the cells of the macrophage lineage, while CD163 and stabilin-1 were considered as M2-like macrophage biomarkers. Nine patients who died from non-cardiovascular causes comprised the control group. Results: The figure (Figure 1) demonstrates results of immunohistochemical analysis. In the control group the number of CD68+ and CD163+ macrophages was lower than in the infarct, peri-infarct and non-infarct areas during all phases of MI (p < 0.001). Simultaneously the quantity of stabilin-1+ cells in the control group was higher in all the areas during inflammatory phase of MI (p=0.01). We noticed that numbers of CD68+, CD163+ and stabilin-1+ macrophages depended on MI phase. The number of CD68+ cells correlated with the day of MI: strong positive correlation was found in the infarct area (R=0.67, p=0.001) and moderate positive correlation was noticed in the peri-infarct area (R=0.55, p < 0.001). There was similar relationship for CD163+ (infarct area: R=0.61, p=0.001; peri-infarct area: R=0.66, p < 0.001) and stabilin-1+ cells (infarct area: R=0.6, p < 0.001; peri-infarct area: R=0.42, p=0.007). Conclusions: Our study translated experimental knowledge regarding macrophage subpopulations in post-infarction myocardial regeneration into clinical. We observed cardiac macrophage response following MI reminded a murine model. Our data indicate following: (1) dichotomous M1-M2 model is not sufficient to completely describe functions of macrophage subsets; (2) characterization of macrophage phenotypes by multiple biomarkers is promising; (3) stabilin-1 could be used as macrophage biomarker in cardiac wound healing in patients with MI. Our study supported diagnostic prospects for implementation of macrophage phenotyping in clinic. Identifying effective biomarkers of different macrophage subsets in patients with MI might become the basis of the method to predict adverse cardiac remodeling and the first step to develop myocardial regeneration target therapy

M2 cardiac macrophages in wound healing following myocardial infarction: translation to clinic

Funding Acknowledgements: This work was supported by the Russian Foundation for Basic Research (grant №16-04-01268

M2 cardiac macrophages in wound healing following myocardial infarction: translation to clinic

Funding Acknowledgements: This work was supported by the Russian Foundation for Basic Research (grant №16-04-01268

Pseudo-coronary scenario of inflammatory viral cardiomyopathy

Cardiomyopathy is one of the most severe and complicated cardiovascular diseases which leads to development of acute and chronic heart failure. The progress in molecular biochemistry and genetics allows to significant enhancement of its diagnostics. New data has confirmed that cardiomyopathies represent a comple