A transmural gradient of myocardial remodeling in early‐stage heart failure with preserved ejection fraction in the pig

Mühlfeld, Christian; Rajces, Alexandra; Manninger, Martin; Alogna, Alessio; Wierich, Marie-Christin; Scherr, Douglas S.; Post, Heiner; Schipke, Julia

doi:10.1111/joa.13117

Cited by 11 publications

(10 citation statements)

References 30 publications

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“…With a more limited coronary microembolization than in the creation of heart failure with reduced ejection fraction, dogs developed heart failure with preserved ejection fraction [ 81 ]. In pigs with corticosterone-induced hypertension, heart failure with preserved ejection fraction developed and was characterized by decreased coronary reserve, [ 192 ] but no alteration in capillary density [ 152 ]. Pigs with chronic aortic banding developed LV hypertrophy with both systolic and diastolic dysfunction but still had preserved ejection fraction; [ 51 ] in this model, the increment in coronary blood flow for a given increase in myocardial oxygen consumption during pressure load was attenuated, suggesting impaired metabolic coronary vasodilation [ 51 ].…”

Section: Heart Failure Of Ischemic and Non-ischemic Originmentioning

confidence: 99%

Coronary blood flow in heart failure: cause, consequence and bystander

Heusch

2022

Basic Res Cardiol

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Heart failure is a clinical syndrome where cardiac output is not sufficient to sustain adequate perfusion and normal bodily functions, initially during exercise and in more severe forms also at rest. The two most frequent forms are heart failure of ischemic origin and of non-ischemic origin. In heart failure of ischemic origin, reduced coronary blood flow is causal to cardiac contractile dysfunction, and this is true for stunned and hibernating myocardium, coronary microembolization, myocardial infarction and post-infarct remodeling, possibly also for the takotsubo syndrome. The most frequent form of non-ischemic heart failure is dilated cardiomyopathy, caused by genetic mutations, myocarditis, toxic agents or sustained tachyarrhythmias, where alterations in coronary blood flow result from and contribute to cardiac contractile dysfunction. Hypertrophic cardiomyopathy is caused by genetic mutations but can also result from increased pressure and volume overload (hypertension, valve disease). Heart failure with preserved ejection fraction is characterized by pronounced coronary microvascular dysfunction, the causal contribution of which is however not clear. The present review characterizes the alterations of coronary blood flow which are causes or consequences of heart failure in its different manifestations. Apart from any potentially accompanying coronary atherosclerosis, all heart failure entities share common features of impaired coronary blood flow, but to a different extent: enhanced extravascular compression, impaired nitric oxide-mediated, endothelium-dependent vasodilation and enhanced vasoconstriction to mediators of neurohumoral activation. Impaired coronary blood flow contributes to the progression of heart failure and is thus a valid target for established and novel treatment regimens.

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Section: Heart Failure Of Ischemic and Non-ischemic Originmentioning

confidence: 99%

Coronary blood flow in heart failure: cause, consequence and bystander

Heusch

2022

Basic Res Cardiol

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“…If accounting for lateral contributions of 20%, as previously reported [ 7 ], the global proportion of CX43 should be close to 2% of the cell area. Some studies have suggested that CM represents 80% of volume fraction [ 31 ], but that proportion would be lower for 2D longitudinal sections as compared to 3D volumes. Thus, 2% of CX43 per CM area would be translated into CX43-to-tissue fraction of 1.6% or less.…”

Section: Discussionmentioning

confidence: 99%

Automatic Quantification of Cardiomyocyte Dimensions and Connexin 43 Lateralization in Fluorescence Images

et al. 2020

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Cardiomyocytes’ geometry and connexin 43 (CX43) amount and distribution are structural features that play a pivotal role in electrical conduction. Their quantitative assessment is of high interest in the study of arrhythmias, but it is usually hampered by the lack of automatic tools. In this work, we propose a software algorithm (Myocyte Automatic Retrieval and Tissue Analyzer, MARTA) to automatically detect myocytes from fluorescent microscopy images of cardiac tissue, measure their morphological features and evaluate the expression of CX43 and its degree of lateralization. The proposed software is based on the generation of cell masks, contouring of individual cells, enclosing of cells in minimum area rectangles and splitting of these rectangles into end-to-end and middle compartments to estimate CX43 lateral-to-total ratio. Application to human ventricular tissue images shows that mean differences between automatic and manual methods in terms of cardiomyocyte length and width are below 4 μm. The percentage of lateral CX43 also agrees between automatic and manual evaluation, with the interquartile range approximately covering from 3% to 30% in both cases. MARTA is not limited by fiber orientation and has an optimized speed by using contour filtering, which makes it run hundreds of times faster than a trained expert. Developed for CX43 studies in the left ventricle, MARTA is a flexible tool applicable to morphometric and lateralization studies of other markers in any heart chamber or even skeletal muscle. This open-access software is available online.

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“…There are marked differences in cellular composition during development, between males and females (Squiers et al 2020), between atria and ventricles of the same individual (Litviňuková et al 2020) and between healthy and diseased tissue. Myocardial volume is generally dominated by CM (>60% of tissue volume, Mühlfeld et al 2020). The remaining tissue volume comprises non-CM (such as FB, pericytes, neurons, endothelial cells, immune cells, adipocytes or smooth muscle cells), vascular (arterial, capillary, venous and lymphatic) lumens and ECM (the latter with a volume fraction of ≈2-7%, Díez et al 2002;Borbély et al 2005).…”

Section: Composition Of Cardiac Tissuementioning

confidence: 99%

Passive myocardial mechanical properties: meaning, measurement, models

et al. 2021

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Passive mechanical tissue properties are major determinants of myocardial contraction and relaxation and, thus, shape cardiac function. Tightly regulated, dynamically adapting throughout life, and affecting a host of cellular functions, passive tissue mechanics also contribute to cardiac dysfunction. Development of treatments and early identification of diseases requires better spatio-temporal characterisation of tissue mechanical properties and their underlying mechanisms. With this understanding, key regulators may be identified, providing pathways with potential to control and limit pathological development. Methodologies and models used to assess and mimic tissue mechanical properties are diverse, and available data are in part mutually contradictory. In this review, we define important concepts useful for characterising passive mechanical tissue properties, and compare a variety of in vitro and in vivo techniques that allow one to assess tissue mechanics. We give definitions of key terms, and summarise insight into determinants of myocardial stiffness in situ. We then provide an overview of common experimental models utilised to assess the role of environmental stiffness and composition, and its effects on cardiac cell and tissue function. Finally, promising future directions are outlined.

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A transmural gradient of myocardial remodeling in early‐stage heart failure with preserved ejection fraction in the pig

Cited by 11 publications

References 30 publications

Coronary blood flow in heart failure: cause, consequence and bystander

Coronary blood flow in heart failure: cause, consequence and bystander

Automatic Quantification of Cardiomyocyte Dimensions and Connexin 43 Lateralization in Fluorescence Images

Passive myocardial mechanical properties: meaning, measurement, models

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