Changes In Myocardial Stiffness Research Articles

The Role of Titin Phosphorylation in Changes in Myocardial Stiffness in Cardiomyopathies

The review provides a brief analysis of current knowledge about such post-translational modification of titin as phosphorylation, with an emphasis on the changes that occur during the development of heart diseases. Studies conducted using animal models of heart disease, as well as using biomaterial from cardiac tissue from patients with various pathologies, show changes in the level of titin phosphorylation in comparison with healthy controls. As a rule, hyperphosphorylation of the S11878 site and hypophosphorylation of the S12022 site in the PEVK sequence of titin are observed, as well as changes in the level of phosphorylation of sites in the N2B sequence of this protein during the development of pathological changes. The functional effect of these changes is an increase in the stiffness of cardiomyocytes and cardiac muscle as a whole, which is based on the viscoelastic properties of titin, changes in which, in turn, are observed due to hypo- or hyperphosphorylation of certain sites of this protein. The review also provides a description of a number of therapeutic interventions aimed at changing the level of titin phosphorylation, which are considered as a way to change the viscoelastic properties of pathological myocardium in order to normalize its contractility.

Role of Titin Phosphorylation in Myocardial Stiffness Changes during Cardiomyopathies

Role of Titin Phosphorylation in Myocardial Stiffness Changes during Cardiomyopathies

Natural shear waves show sequential changes in myocardial stiffness In paediatric multi-inflammatory systemic syndrome post COVID

Abstract Funding Acknowledgements Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Egyptian ministry of research and higher education Background Multi-inflammatory systemic syndrome post COVID infection (MIS-C) in children causes myocarditis and affects myocardial diastolic function. Recent high frame rate echocardiography allows to assess myocardial shear waves (SW). SW are mechanical waves generated by mitral and aortic valve closure (MVC & AVC). Their propagation velocities are related to myocardial stiffness (MS), a determinant of diastolic function. Nevertheless, this has not yet been tested in paediatric cardiology and in this pathology. Purpose This study aimed at exploring the changes in natural SW propagation velocity as measure of myocardial diastolic properties in paediatric patients with MIS-C. Methods Seven MIS-C children (mean age 6.7 ±3.6 years) were prospectively followed over 6 months (group A). As a control group; one hundred-four healthy volunteers (HV) (mean age 10.2 ±4.4 years) were recruited (group B). High-frame rate echocardiography was used to obtain parasternal long axis views of all subjects at a frame rate of 1580 ±113 Hz. An anatomical M-mode was drawn along the interventricular septum and Tissue Doppler acceleration maps were extracted to measure SW propagation speed after MVC and AVC (Figure 1). Independent sample t-test was used to compare between both groups. Repeated measures analysis of variance (ANOVA) was used to show sequential changes during follow-up. Results SW propagation velocities were significantly higher among MIS-C patients than in HV group after both MVC (4.3 ±0.6 m/s vs 2.8 ±0.3 m/s respectively, p<0.001) and AVC (5.2 ±0.6 m/s vs 3.0 ±0.3 m/s respectively; p<0.001). Interestingly, SW propagation speeds in MIS-C patients declined significantly with myocardial recovery during course of disease (figure 2) and normalised 6 months post discharge (MVC: 2.9 ±0.3 m/s; P<0.001, AVC: 3.2 ±0.4 m/s; P<0.001) compared to admission. Conclusions SW speed found to be 1.5 to 1.7 fold higher with myocardial inflammation in MIS-C patients compared to HV. Values normalised within 6 months. These findings indicate that SW velocities can show sequential changes in the course of a disease and suggest that SW imaging has potential to serve as a new non-invasive diagnostic tool in paediatric cardiac diseases.

Abstracts from the NIH Office of Research on Women's Health 2022 Annual BIRCWH Meeting:Building Interdisciplinary Research Careers in Women's Health November 2, 2022

Abstracts from the NIH Office of Research on Women's Health 2022 Annual BIRCWH Meeting:Building Interdisciplinary Research Careers in Women's Health November 2, 2022

Impact of Loading and Myocardial Mechanical Properties on Natural Shear Waves: Comparison to Pressure-Volume Loops

BackgroundShear wave elastography (SWE) has been proposed as a novel noninvasive method for the assessment of myocardial stiffness, a relevant determinant of diastolic function. It is based on tracking the propagation of shear waves, induced, for instance, by mitral valve closure (MVC), in the myocardium. The speed of propagation is directly related to myocardial stiffness, which is defined by the local slope of the nonlinear stress-strain relation. Therefore, the operating myocardial stiffness can be altered by both changes in loading and myocardial mechanical properties. ObjectivesThis study sought to evaluate the capability of SWE to quantify myocardial stiffness changes in vivo by varying loading and myocardial tissue properties and to compare SWE against pressure-volume loop analysis, a gold standard reference method. MethodsIn 15 pigs, conventional and high–frame rate echocardiographic data sets were acquired simultaneously with pressure-volume loop data after acutely changing preload and afterload and after inducting an ischemia/reperfusion (I/R) injury. ResultsShear wave speed after MVC significantly increased by augmenting preload and afterload (3.2 ± 0.8 m/s vs 4.6 ± 1.2 m/s and 4.6 ± 1.0 m/s, respectively; P = 0.001). Preload reduction had no significant effect on shear wave speed compared to baseline (P = 0.118). I/R injury resulted in significantly higher shear wave speed after MVC (6.1 ± 1.2 m/s; P < 0.001). Shear wave speed after MVC had a strong correlation with the chamber stiffness constant β (r = 0.63; P < 0.001) and operating chamber stiffness dP/dV before induction of an I/R injury (r = 0.78; P < 0.001) and after (r = 0.83; P < 0.001). ConclusionsShear wave speed after MVC was influenced by both acute changes in loading and myocardial mechanical properties, reflecting changes in operating myocardial stiffness, and was strongly related to chamber stiffness, invasively derived by pressure-volume loop analysis. SWE provides a novel noninvasive method for the assessment of left ventricular myocardial properties.

Abstract 482: Assessing myocardial stiffness changes in a non-human primate anthracycline-induced cardiotoxicity model utilizing a biomechanical elasticity imaging methodology

Abstract Scope: Anthracyclines are a routine regimen for adjuvant therapy of breast cancer, but pose dose-dependent cardiotoxicity risks. With breast cancer diagnoses trending younger, there is a critical need for accurate non-invasive methods for assessing early cardiac degradation for mitigating cardiotoxicity due to cancer therapies. Methods: We developed a biomechanical model-based elasticity imaging method (BEIM) for assessing direct, functional mechanical stiffness of the left ventricle (LV) to indicate early cardiac degradation1. In this study, we examined the use of BEIM in a cohort of 5 African Green monkeys (AGM) receiving human equivalent doses of doxorubicin (cumulative dose: 240mg/m2) over 10 weeks. Cardiac magnetic resonance (CMR) imaging was acquired before and 15 weeks after final doxorubicin dose. Mechanical elasticity was estimated throughout the mid-plane of the LV utilizing BEIM. After necropsy, histopathology with picrosirius red of the matching LV mid-plane was conducted at 15 weeks after the final doxorubicin dose to calculate collagen volume fraction (CVF) indicative of anthracycline-associated cardiac fibrosis. Archival, age-and gender-matched LVs from healthy, chemotherapy naïve AGM were used as histopathological controls. Results: Two-dimensional circumferential, radial, and shear elasticity maps of the mid-plane of the LV indicate substantial changes in mechanical elasticity between baseline and 15 weeks post-doxorubicin CMR acquisitions. Average global change between baseline and post-doxorubicin image acquisitions in circumferential, radial, and shear modulus were 4.8, 5.7, and 5.2-fold increases respectively, with an average 1.9-fold change of CVF. Global circumferential, radial, and shear modulus values at baseline and 15 weeks post-doxorubicin were compared to CVF values for each subject and indicate a very strong correlation between circumferential, radial, and shear modulus with CVF, represented by Pearson’s correlation coefficients of 0.91, 0.92, and 0.89, respectively. Conclusions: We developed BEIM to assess changes in LV mechanical elasticity utilizing routine CMR imaging data with a goal of non-invasively identifying cardiac stiffening associated with cardiotoxicity. To validate our methodology, we utilized CMR data from an AGM model of anthracycline-induced cardiotoxicity to estimate changes in LV elasticity and compare to CVF values from histopathology. Our results show an increase in both CVFs and mechanical elasticity between baseline and 15 weeks following the last doxorubicin dose. Elasticity measures exhibit a very strong correlation with histopathological assessment of cardiac fibrosis. Results demonstrate the ability of our BEIM to identify changes in elasticity related to increased collagen deposition from anthracycline-induced cardiotoxicity. Citation Format: Caroline Miller, Jennifer H. Jordan, Alexandra Thomas, Giselle Meléndez, Jared A. Weis. Assessing myocardial stiffness changes in a non-human primate anthracycline-induced cardiotoxicity model utilizing a biomechanical elasticity imaging methodology [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 482.

A guide for assessment of myocardial stiffness in health and disease

Myocardial stiffness is an intrinsic property of the myocardium that influences both diastolic and systolic cardiac function. Myocardial stiffness represents the resistance of this tissue to being deformed and depends on intracellular components of the cardiomyocyte, particularly the cytoskeleton, and on extracellular components, such as collagen fibers. Myocardial disease is associated with changes in myocardial stiffness, and its assessment is a key diagnostic marker of acute or chronic pathological myocardial disease with the potential to guide therapeutic decision-making. In this Review, we appraise the different techniques that can be used to estimate myocardial stiffness, evaluate their advantages and disadvantages, and discuss potential clinical applications. This Review discusses the physical concepts and descriptions of the structures that determine myocardial stiffness, different techniques used to estimate myocardial stiffness, and their application in clinical medicine.

Developing a biomechanical model-based elasticity imaging method for assessing hormone receptor positive breast cancer treatment-related myocardial stiffness changes.

Purpose: Assessing cardiotoxicity as a result of breast cancer therapeutics is increasingly important as breast cancer diagnoses are trending younger and overall survival is increasing. With evidence showing that prevention of cardiotoxicity plays a significant role in increasing overall survival, there is an unmet need for accurate non-invasive methods to assess cardiac injury due to cancer therapies. Current clinical methods are too coarse and emerging research methods have not yet achieved clinical implementation. Approach: As a proof of concept, we examine myocardial elasticity imaging in the setting of premenopausal women diagnosed with hormone receptor positive (HR-positive) breast cancer undergoing severe estrogen depletion, as cardiovascular injury from early estrogen depletion is well-established. We evaluate the ability of our model-based cardiac elasticity imaging analysis method to indicate subclinical cancer therapy-related cardiac decline by examining differences in the change in cardiac elasticity over time in two cohorts of premenopausal women either undergoing severe estrogen depletion for HR-positive breast cancer or triple negative breast cancer patients as comparators. Results: Our method was capable of producing functional mechanical elasticity maps of the left ventricle (LV). Using these elasticity maps, we show significant differences in cardiac mechanical elasticity in the HR-positive breast cancer cohort compared to the comparator cohort. Conclusions: We present our methodology to assess the mechanical stiffness of the LV by interrogating cardiac magnetic resonance images within a computational biomechanical model. Our preliminary study suggests the potential of this method for examining cardiac tissue mechanical stiffness properties as an early indicator of cardiac decline.

Interplay of Genotype and Substrate Stiffness in Driving the Hypertrophic Cardiomyopathy Phenotype in iPSC-Micro-Heart Muscle Arrays.

In clinical and animal studies, Hypertrophic Cardiomyopathy (HCM) shares many similarities with non-inherited cardiac hypertrophy induced by pressure overload (hypertension). This suggests a potential role for mechanical stress in priming tissues with mutation-induced changes in the sarcomere to develop phenotypes associated with HCM, including hypercontractility and aberrant calcium handling. Here, we tested the hypothesis that heterozygous loss of function of Myosin Binding Protein C (MYBCP3 +/- , mutations in which account for almost 50% of inherited HCM) combines with environmental stiffness to drive HCM phenotypes. We differentiated isogenic control (WTC) and MYBPC3 +/- iPSC into cardiomyocytes using small molecule manipulation of Wnt signaling, and then purified them using lactate media. The purified cardiomyocytes were seeded into "dog bone" shaped stencil molds to form micro-heart muscle arrays (μHM). To mimic changes in myocardial stiffness stemming from pressure overload, we varied the rigidity of the substrates μHM contract against. Stiffness levels ranged from those corresponding to fetal (5 kPa), healthy (15 kPa), pre-fibrotic (30 kPa) to fibrotic (65 kPa) myocardium. Substrates were embedded with a thin layer of fluorescent beads to track contractile force, and parent iPSC were engineered to express the genetic calcium indicator, GCaMP6f. High speed video microscopy and image analysis were used to quantify calcium handling and contractility of μHM. Substrate rigidity triggered physiological adaptation for both genotypes. However, MYBPC3 +/- μHM showed a lower tolerance to substrate stiffness with the peak traction on 15 kPa, while WTC μHM had peak traction on 30 kPa. MYBPC3 +/- μHM exhibited hypercontractility, which was exaggerated by substrate rigidity. MYBPC3 +/- μHM hypercontractility was associated with longer rise times for calcium uptake and force development, along with higher overall Ca2+ intake. We found MYBPC3 +/- mutations cause iPSC-μHM to exhibit hypercontractility, and also a lower tolerance for mechanical stiffness. Understanding how genetics work in combination with mechanical stiffness to trigger and/or exacerbate pathophysiology may lead to more effective therapies for HCM. The online version contains supplementary material available at (10.1007/s12195-021-00684-x).

Shear wave cardiovascular MR elastography using intrinsic cardiac motion for transducer-free non-invasive evaluation of myocardial shear wave velocity

Changes in myocardial stiffness may represent a valuable biomarker for early tissue injury or adverse remodeling. In this study, we developed and validated a novel transducer-free magnetic resonance elastography (MRE) approach for quantifying myocardial biomechanics using aortic valve closure-induced shear waves. Using motion-sensitized two-dimensional pencil beams, septal shear waves were imaged at high temporal resolution. Shear wave speed was measured using time-of-flight of waves travelling between two pencil beams and corrected for geometrical biases. After validation in phantoms, results from twelve healthy volunteers and five cardiac patients (two left ventricular hypertrophy, two myocardial infarcts, and one without confirmed pathology) were obtained. Torsional shear wave speed in the phantom was 3.0 ± 0.1 m/s, corresponding with reference speeds of 2.8 ± 0.1 m/s. Geometrically-biased flexural shear wave speed was 1.9 ± 0.1 m/s, corresponding with simulation values of 2.0 m/s. Corrected septal shear wave speeds were significantly higher in patients than healthy volunteers [14.1 (11.0–15.8) m/s versus 3.6 (2.7–4.3) m/s, p = 0.001]. The interobserver 95%-limits-of-agreement in healthy volunteers were ± 1.3 m/s and interstudy 95%-limits-of-agreement − 0.7 to 1.2 m/s. In conclusion, myocardial shear wave speed can be measured using aortic valve closure-induced shear waves, with cardiac patients showing significantly higher shear wave speeds than healthy volunteers. This non-invasive measure may provide valuable insights into the pathophysiology of heart failure.

Characterization of Regional Changes in Myocardial Strain and Stiffness after Myocardial Infarction using Speckle‐Tracking Echocardiography in Swine

ObjectiveLeft ventricular (LV) remodeling following myocardial infarction (MI) is characterized by dynamic changes in myocardial structure and function in infarcted as well as remote, non‐infarcted myocardium. Speckle‐Tracking Echocardiography (STE) offers a sensitive, non‐invasive approach to assess myocardial mechanical properties and may be useful for evaluating regional changes in tissue mechanics after MI. In the present study, STE‐derived strain analysis was combined with measurements of LV pressure to quantify regional alterations in myocardial stiffness in a porcine model of reperfused MI.MethodsPropofol‐anesthetized swine (n=8) were subjected to a 90 minute balloon occlusion of the distal left anterior descending coronary artery to produce MI. Peak strain values were acquired in radial, circumferential, and longitudinal directions via STE (Vivid 7; GE) at baseline and 1 month post‐MI. Circumferential diastolic stiffness was derived in vivo from stress‐strain relationships obtained via pressure catheter measurements of LV minimum and end‐diastolic pressure. Myocardial tissue samples were subsequently collected from corresponding infarcted and remote regions of the left ventricle for direct assessment of passive stiffness via post‐mortem uniaxial tensile testing.ResultsMeasurements of LV end‐diastolic volume (from 75±5 mL at baseline to 105±7 mL 1 month post‐MI, p&lt;0.001) and LV ejection fraction (from 68±1 % to 53±2 %, p&lt;0.001) were consistent with expected changes in LV structure and function associated with post‐infarction remodeling (infarct size: 6.7±0.7 % of LV). Serial STE revealed significant reductions in radial, circumferential, and longitudinal strain 1 month after MI that were comparable between infarct and remote segments (Table). In concordance with reductions in strain, infarct and remote segments each exhibited a significant increase in circumferential stiffness. However, the magnitude of this increase in stiffness was lower than that derived from post‐mortem measurements of passive stiffness, particularly in the infarct region (infarct scar: 584±156 kPa; remote myocardium: 96±16 kPa).ConclusionsThese results demonstrate the ability of STE to detect regional alterations in myocardial function after MI and highlight the importance of evaluating mechanical properties of remote non‐infarcted areas of the left ventricle that exhibit comparable changes in strain to that observed in the infarct segment. The addition of direct LV pressure measurements allows assessment of regional changes in myocardial stiffness, although further studies are necessary to understand the discrepancy in stiffness derived from STE vs. post‐mortem tensile testing, particularly in infarcted segments of the left ventricle.Support or Funding InformationThe National Heart Lung and Blood Institute (HL‐061610), the American Heart Association (17SDG33660200), the National Center for Advancing Translational Sciences (UL1TR001412), the Department of Veterans Affairs (1IO1BX002659), and the Albert and Elizabeth Rekate Fund in Cardiovascular Medicine.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Repercussões cardíacas após infarto do miocárdio em ratas submetidas previamente a exercício físico

Few studies have analyzed the cardiac effects of exercise prior to coronary occlusion. To evaluate the effects of myocardial infarction in rats undergoing physical exercise. Female rats underwent swimming exercise or were kept sedentary for eight weeks and were randomized to coronary occlusion or sham surgery, in one of the following four groups: Sedentary (S), exercise (E), Sedentary myocardial infarction (SMI) and Exercise myocardial infarction (EMI). After six weeks, their biometrics, Doppler echocardiography, hemodynamics and myocardial mechanics were analyzed. No cardioprotection was observed in EMI animals and there was no difference in infarct size (%LV) between EMI (38.50 ± 4.60%) and SMI (36.58 ± 4.11%). Water content of the lung (%) of SMI (80 ± 0.59) and EMI (80 ± 0.57) was higher than that of S (78 ± 0.15) and E (78 ± 0.57) groups. Left ventricular systolic pressure (mmHg) (S: 130 ± 5, E: 118 ± 8; SMI: 91 ± 3; EMI: 98 ± 3) and the first positive time derivative (mmHg) positive pressure (S: 8216 ± 385; E: 8437 ± 572; SMI: 4674 ± 455; EMI: 5080 ± 412) of S and E were higher than those of SMI and EMI. The transverse fractional shortening (%) of SMI (27 ± 2) and EMI (25 ± 2) were similar and lower than that of E (65 ± 2) and S (69 ± 2). The E/A ratio was higher in SMI (5.14 ± 0.61) and EMI (4.73 ± 0.57) compared to S (2.96 ± 0.24) and E (2.83 ± 0 21). In studies of isolated papillary muscle, depression of the contractile capacity observed was similar to that of SMI and EMI, and there was no change in myocardial stiffness. Previous training by swimming did not attenuate cardiac implications due to myocardial infarction.

Acoustic Radiation Force Impulse Imaging of Mechanical Stiffness Propagation in Myocardial Tissue

Acoustic radiation force impulse (ARFI) imaging has been shown to be capable of imaging local myocardial stiffness changes throughout the cardiac cycle. Expanding on these results, the authors present experiments using cardiac ARFI imaging to visualize and quantify the propagation of mechanical stiffness during ventricular systole. In vivo ARFI images of the left ventricular free wall of two exposed canine hearts were acquired. Images were formed while the heart was externally paced by one of two electrodes positioned on the epicardial surface and either side of the imaging plane. Two-line M-mode ARFI images were acquired at a sampling frequency of 120 Hz while the heart was paced from an external stimulating electrode. Two-dimensional ARFI images were also acquired, and an average propagation velocity across the lateral field of view was calculated. Directions and speeds of myocardial stiffness propagation were measured and compared with the propagations derived from the local electrocardiogram (ECG), strain, and tissue velocity measurements estimated during systole. In all ARFI images, the direction of myocardial stiffness propagation was seen to be away from the stimulating electrode and occurred with similar velocity magnitudes in either direction. When compared with the local epicardial ECG, the mechanical stiffness waves were observed to travel in the same direction as the propagating electrical wave and with similar propagation velocities. In a comparison between ARFI, strain, and tissue velocity imaging, the three methods also yielded similar propagation velocities.

In Vivo Assessment of Myocardial Stiffness with Acoustic Radiation Force Impulse Imaging

Acoustic radiation force impulse (ARFI) imaging has been demonstrated to be capable of visualizing variations in local stiffness within soft tissue. Recent advances in ARFI beam sequencing and parallel imaging have shortened acquisition times and lessened transducer heating to a point where ARFI acquisitions can be executed at high frame rates on commercially available diagnostic scanners. In vivo ARFI images were acquired with a linear array placed on an exposed canine heart. The electrocardiogram (ECG) was also recorded. When coregistered with the ECG, ARFI displacement images of the heart reflect the expected myocardial stiffness changes during the cardiac cycle. A radio-frequency ablation was performed on the epicardial surface of the left ventricular free wall, creating a small lesion that did not vary in stiffness during a heartbeat, though continued to move with the rest of the heart. ARFI images showed a hemispherical, stiffer region at the ablation site whose displacement magnitude and temporal variation through the cardiac cycle were less than the surrounding untreated myocardium. Sequences with radiation force pulse amplitudes set to zero were acquired to measure potential cardiac motion artifacts within the ARFI images. The results show promise for real-time cardiac ARFI imaging. (E-mail: stephen.j.hsu@duke.edu)

Constitutive properties of hypertrophied myocardium: cellular contribution to changes in myocardial stiffness.

Recent studies have suggested that pressure overload hypertrophy (POH) alters the viscoelastic properties of individual cardiocytes when studied in isolation. However, whether these changes in cardiocyte properties contribute causally to changes in the material properties of the cardiac muscle as a whole is unknown. Accordingly, a selective, isolated, acute change in cardiocyte constitutive properties was imposed in an in vitro system capable of measuring the resultant effect on the material properties of the composite cardiac muscle. POH caused an increase in both myocardial elastic stiffness, from 20.5 +/- 1.3 to 28.4 +/- 1.8, and viscous damping, from 15.2 +/- 1.1 to 19.8 +/- 1.5 s (normal vs. POH, P < 0.05), respectively. Recent studies have shown that cardiocyte constitutive properties could be acutely altered by depolymerizing the microtubules with colchicine. Colchicine caused a significant decrease in the viscous damping in POH muscles (19.8 +/- 1.5 s at baseline vs. 14.7 +/- 1.3 s after colchicine, P < 0.05). Therefore, myocardial material properties can be altered by selectively changing the constitutive properties of one element within this muscle tissue, the cardiocyte. Changes in the constitutive properties of the cardiocytes themselves contribute to the abnormalities in myocardial stiffness and viscosity that develop during POH.

New concepts in diastolic dysfunction and diastolic heart failure: Part II: causal mechanisms and treatment.

As described in Part I of this 2-part article,1 diastolic heart failure is common and causes significant alterations in prognosis. In Part II, experimental studies that have provided insight into the mechanisms that cause diastolic heart failure will be described.2–19⇓⇓⇓⇓⇓⇓⇓⇓⇓⇓⇓⇓⇓⇓⇓⇓⇓ In addition, current treatment strategies and the design of future clinical trials of diastolic heart failure will be discussed. The development of truly effective therapy for diastolic heart failure depends on gaining a clear understanding of the basic mechanisms that alter diastolic function and the ability to efficiently target these mechanisms to correct these abnormalities in diastolic function. Conceptually, the mechanisms that cause abnormalities in diastolic function that lead to the development of diastolic heart failure can be divided into factors intrinsic to the myocardium itself (myocardial) and factors that are extrinsic to the myocardium (extramyocardial; Table 1). Myocardial factors can be divided into structures and processes within the cardiac muscle cell (cardiomyocyte), within the extracellular matrix (ECM) that surrounds the cardiac muscle cell, and that activate the autocrine or paracrine production of neurohormones. Each of these mechanisms are active in the major pathological processes that result in diastolic dysfunction and heart failure. Myocardial and extramyocardial mechanisms, cellular and extracellular mechanisms, and neurohumoral activation each play a role in the development of diastolic heart failure caused by ischemia, pressure-overload hypertrophy, and restrictive and hypertrophic cardiomyopathy. View this table: Table 1105290. Diastolic Heart Failure: Mechanisms ### Cardiomyocyte Diastolic dysfunction can be caused by mechanisms that are intrinsic to the cardiac muscle cells themselves. These include changes in calcium homeostasis caused by (1) abnormalities in the sarcolemmal channels responsible for short- and long-term extrusion of calcium from the cytosol, such as the sodium calcium exchanger and the calcium pump; (2) …

Cyclic changes in myocardial stiffness over the cardiac cycle as measured using a new ultrasound method, vibro-acoustography: findings in normal and infarcted myocardium

Cyclic changes in myocardial stiffness over the cardiac cycle as measured using a new ultrasound method, vibro-acoustography: findings in normal and infarcted myocardium

Regional Myocardial Stiffness Measured by a New Tactile Sensor System.

Numerous investigators have attempted to measure regional wall stress directly. However, the measurement systems and devices employed have been too complex for accurate quantification in situ. We have developed a new tactile sensor system for measuring accurately myocardial stiffness in situ and validated its use for estimation of myocardial contractile function. The tactile sensor was placed on the left ventricle of five mongrel dogs, (weighing 12-17 kg) and myocardial stiffness (g/mm2) was measured. Dobutamine (5.0 micrograms/kg/min) and propranolol (0.25 mg/kg) were sequentially administrated intravenously, and the change in myocardial stiffness was monitored. Myocardial stiffness followed a time course similar to that of left ventricular pressure, indicating a close relationship with wall stress. Baseline end-systolic stiffness in 5 dogs was 2.38 +/- 0.19 g/mm2. After administration of dobutamine, end-systolic stiffness increased to 3.26 +/- 0.32 g/mm2 (p < 0.01). After the administration of propranolol, end-systolic stiffness decreased significantly to 1.83 +/- 0.19 g/mm2 (p < 0.01), compared with the baseline values. Regional myocardial stiffness of a beating heart can be measured precisely using our new tactile sensor system. End-systolic stiffness is a useful index for accurate quantification of the regional myocardial contractile state.

Effects of pressure- or volume-overload hypertrophy on passive stiffness in isolated adult cardiac muscle cells.

It has been hypothesized that the changes in myocardial stiffness induced by chronic hemodynamic overloading are dependent on changes in the passive stiffness of the cardiac muscle cell (cardiocyte). However, no previous studies have examined the passive constitutive properties of cardiocytes isolated from animals with myocardial hypertrophy. Accordingly, changes in relative passive stiffness of cardiocytes isolated from animals with chronic pressure- or volume-overload hypertrophy were determined by examining the effects of anisosmotic stress on cardiocyte size. Anisosmotic stress was produced by altering superfusate osmolarity. Hypertrophied cardiocytes were enzymatically isolated from 16 adult cats with right ventricular (RV) pressure-overload hypertrophy induced by pulmonary artery banding (PAB) and from 6 adult cats with RV volume-overload hypertrophy induced by creating an atrial septal defect (ASD). Left ventricular (LV) cardiocytes from each cat served as nonhypertrophied, normally loaded, same-animal controls. Superfusate osmolarity was decreased from 305 +/- 3 to 135 +/- 5 mosM and increased to 645 +/- 4 mosM. During anisosmotic stress, there were no significant differences between hypertrophied RV and normal LV cardiocytes in pressure overload PAB cats with respect to percent change in cardiocyte area (47 +/- 2% in RV vs. 48 +/- 2% in LV), diameter (46 +/- 3% in RV vs. 48 +/- 2% in LV), or length (2.4 +/- 0.2% in RV vs. 2.0 +/- 0.3% in LV), or sarcomere length (1.5 +/- 0.1% in RV vs. 1.3 +/- 0.3% in LV). Likewise, there were no significant differences in cardiocyte strain between hypertrophied RV and normal LV cardiocytes from ASD cats. In conclusion, chronic pressure-overload hypertrophy and chronic volume-overload hypertrophy did not alter the cardiocyte response to anisosmotic stress. Thus chronic overload hypertrophy did not alter relative passive cardiocyte stiffness.

Myocardial segment motion during regional ischemia--regional contraction and relaxation.

Several aspects of regional ischemic myocardial function determined by segment motion are discussed, based on our studies. Although global left ventricular function decreased progressively as the global severity of myocardial ischemia increased, there are several possible factors which may modify this relationship. As for the site of the ischemic area, occlusion of the left anterior descending artery resulted in a greater decrease in the left ventricular ejection fraction than occlusion of the left circumflex artery. Interaction between the ischemic myocardium and the non-ischemic myocardium may be a multifactorial phenomenon rather than simple tandem stretching. The segment length motion during acute ischemia appears to be complicated. The segment motion of the severe ischemic myocardium during systole and diastole was explained for the most part by a uniform tension-length curve which was independent of changes in the loading condition. This non-linear elastic property was fundamental to the production of segment motion asynchrony. The wall motion of the hypokinetic segment might be explained by a combination of the active change in myocardial stiffness and the non-linear elastic property of the myocardium.