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At least 217 records · Page 12Linked to original sources
PubMed1999

Cell-derived stiffening and plasticizing factors in sea cucumber (Cucumaria frondosa) dermis

The stiffness of holothurian dermis can be altered experimentally in vitro by changing the concentration of extracellular Ca(2+). Previous experiments with Cucumaria frondosa have established that these Ca(2+) effects are due to Ca(2+)-dependent cellular processes rather than to direct effects of Ca(2+) on the extracellular matrix. The present report describes two protein factors that are released from cells of C. frondosa dermis by membrane lysis and that directly alter the stiffness of the extracellular matrix. One factor, isolated from the inner dermis, increased tissue stiffness in the absence of Ca(2+). The second factor, from the outer dermis, decreased tissue stiffness in the presence of normal Ca(2+) levels. The relative abundance of these two factors in the inner and outer dermis suggests the possibility that the cells that control tissue stiffness are spatially segregated. Both factors were partially purified under non-denaturing conditions by anion-exchange and gel-filtration chromatography. The partially purified protein preparations retained biological activity. These results suggest that the stiffness of sea cucumber dermis is regulated by cell-mediated secretion of either the stiffening or plasticizing protein and that alterations in dermis stiffness brought about by manipulation of Ca(2+) levels are mediated by effects on secretion of one or both of these proteins.

Journal Article↗
PubMed2003

Mechanical asymmetry in the embryonic chick heart during looping.

Cardiac looping, which begins with ventral bending and rightward rotation of the primitive heart tube, is an essential morphogenetic event that occurs early in vertebrate development. The biophysical mechanism that drives this process is unknown. It has been speculated that increased stiffness along the dorsal side of the ventricle combined with an intrinsic cardiac force causes the heart to bend. There is no experimental support for this hypothesis, however, since little is known about regional mechanical properties of the heart during looping. We directly measured diastolic stiffness of the inner curvature (IC), outer curvature (OC), and dorsal-ventral sides of the stage 12 chick heart by microindentation. The IC of intact hearts was found to be significantly stiffer than either the OC or the sides. which were of similar stiffness. Isolated cardiac jelly, which is a thick, extracellular matrix compartment underlying the myocardium, was approximately an order of magnitude softer than intact hearts. The results of a computational model simulating the indentation experiments, combined with the stiffness measurements, suggests the regional variation in stiffness is due to the material properties of the myocardium. A second model shows that a relatively stiff IC may facilitate bending of the heart tube during looping.

Animals↗
PubMed1993

Mechanical function and histological structure of the arterial wall. The response to antihypertensive treatment.

Alterations in the structure and function of large arteries could be a major factor in the mortality and morbidity of hypertensive patients. This paper summarises the effects of various pharmacological treatments on the mechanical (functional) properties of large arterial walls and on the structure and composition of these vessels. Firstly, during arterial hypertension, increases in arterial stiffness, associated with medial hypertrophy and/or hyperplasia and alterations in extracellular matrix, are always observed. Sodium intake and aging may influence the arterial wall properties, causing an increase in stiffness, independently of their effect on blood pressure. In parallel, administration of low doses of diuretics to hypertensive rats did not cause significant haemodynamic changes, but did cause an increase in arterial distensibility. Nitrates and derivatives have specific effects on the smooth muscle from large arteries in hypertensive patients. Significant increases in the diameter of large arteries and in arterial wall stiffness have been reported in clinical studies, but these effects have a short time constant. In humans and animals, angiotensin converting enzyme (ACE) inhibitors and calcium antagonists cause relaxation of arterial smooth muscle and, therefore, improve the functional component of the reduced distensibility observed in hypertension. Long term treatment with ACE inhibitors and calcium antagonists induces a significant reduction in medial hypertrophy. However, it is difficult to distinguish between the direct effects resulting from pressure reduction and a specific drug effect.

Animals↗
PubMed2005

Bulk and micropatterned conjugation of extracellular matrix proteins to characterized polyacrylamide substrates for cell mechanotransduction assays.

Increasing numbers of cell mechanotransduction studies are currently utilizing elastic substrates fabricated from polyacrylamide in the form of thin gels. Their versatility depends on the ability to ensure the appropriate gel stiffness and control the uniformity and geometry of extracellular matrix protein coating of the gel. Beginning with a brief quantitative emphasis on the elastic properties of polyacrylamide gels, we present an inexpensive and highly reproducible method for uniform coating with a wide variety of extracellular matrix proteins. We used a reducing agent, hydrazine hydrate, to modify nonreactive amide groups in polyacrylamide to highly reactive hydrazide groups that can form covalent bonds with aldehyde or ketone groups in oxidized proteins. This simple conjugation method overcomes the limitations of previously used photoactivatable cross-linkers: nonuniform coating due to nonuniformity of irradiation and technically challenging procedures for micropatterning. As demonstrated in our study of cell polarity during constrained migration, this conjugation method is especially effective in gel micropatterning by manual microcontact printing of protein patterns as small as 5 microm and enables numerous studies of constrained cell attachment and migration that were previously unfeasible due to high cost or difficulty in controlling the protein coating.

Acrylic Resins↗
PubMedDate not supplied

Periodontal membranes from composites of hydroxyapatite and bioresorbable block copolymers.

Biomembranes are frequently proposed as devices for "guided bone regeneration." Such membranes consist generally of a thin sheet of polymeric material, mostly textured from polymeric yarns or clots, which all have a diffuse very fine winding porosity. The cross-section size of the holes of such porosity is nanometric (diameter < 0.1 microm); thus these holes can be indicated as nanoholes. Whatever the method of production, the surface density of nanoholes (number per square centimeter) has to be as high as possible. It is important also that no variation of this density occurs. The fine dimension of these microholes allows the crossing of small molecules (O2, CO2, H2O, sugars, many nutritional organic compounds and even some simple proteins) but not other larger molecules and particulates, including cells of any kind. These biomembranes have, consequently, a semipermeable behavior, providing the functional role which is the interposition of a barrier for the cells, separating the bone from the surrounding soft tissues. The kinetic of proliferation of osteoblasts is lower than that of fibroblasts. Most membranes of this kind are not resorbable. The main problem for the resorbable ones is the speed of size increase of the holes during the time. Their diameter must not exceed a threshold value until the reconstruction of bone is complete, otherwise soft tissue cells will invade the growing bone tissue with formation of undesirable mixed tissue. The present paper deals with a resorbable membrane made with a composite polymer/ceramic. A poly(epsilon-caprolactone)-block-poly(oxyethylene)-block-poly(epsilon-caprolactone) copolymer is the polymeric matrix which contains dispersed ceramic hydroxyapatite microgranules, a stiff filling additive. The main possible use is that of periodontal membranes. The copolymer, obtained by thermal polymerization of epsilon-caprolactone onto poly(ethylene-glycol), presents good biological tolerance, is resorbable under physiological conditions and can promote cell growth. Histological tests, performed 6 months after implantation, showed that the polymeric matrix is almost totally resorbed. New-formed bone colonizes even the innermost parts of the membrane, with bone trabeculae closely surrounding the hydroxyapatite granules.

Journal Article↗
PubMed2006

A transversely isotropic viscoelastic constitutive equation for brainstem undergoing finite deformation.

The objective of this study was to define the constitutive response of brainstem undergoing finite shear deformation. Brainstem was characterized as a transversely isotropic viscoelastic material and the material model was formulated for numerical implementation. Model parameters were fit to shear data obtained in porcine brainstem specimens undergoing finite shear deformation in three directions: parallel, perpendicular, and cross sectional to axonal fiber orientation and determined using a combined approach of finite element analysis (FEA) and a genetic algorithm (GA) optimizing method. The average initial shear modulus of brainstem matrix of 4-week old pigs was 12.7 Pa, and therefore the brainstem offers little resistance to large shear deformations in the parallel or perpendicular directions, due to the dominant contribution of the matrix in these directions. The fiber reinforcement stiffness was 121.2 Pa, indicating that brainstem is anisotropic and that axonal fibers have an important role in the cross-sectional direction. The first two leading relative shear relaxation moduli were 0.8973 and 0.0741, respectively, with corresponding characteristic times of 0.0047 and 1.4538 s, respectively, implying rapid relaxation of shear stresses. The developed material model and parameter estimation technique are likely to find broad applications in neural and orthopaedic tissues.

Animals↗
PubMed2005

Mechanisms, pathophysiology, and therapy of arterial stiffness.

Arterial stiffness is a growing epidemic associated with increased risk of cardiovascular events, dementia, and death. Decreased compliance of the central vasculature alters arterial pressure and flow dynamics and impacts cardiac performance and coronary perfusion. This article reviews the structural, cellular, and genetic contributors to arterial stiffness, including the roles of the scaffolding proteins, extracellular matrix, inflammatory molecules, endothelial cell function, and reactive oxidant species. Additional influences of atherosclerosis, glucose regulation, chronic renal disease, salt, and changes in neurohormonal regulation are discussed. A review of the hemodynamic impact of arterial stiffness follows. A number of lifestyle changes and therapies that reduce arterial stiffness are presented, including weight loss, exercise, salt reduction, alcohol consumption, and neuroendocrine-directed therapies, such as those targeting the renin-angiotensin aldosterone system, natriuretic peptides, insulin modulators, as well as novel therapies that target advanced glycation end products.

Arteries↗
PubMed2002

[Experimental fusion of the sheep cervical spine. Part I: Effect of cage design on interbody fusion].

INTRODUCTION: There has been a rapid increase in the use of interbody fusion cages as an adjunct to spondylodesis, although experimental data are lacking. A sheep cervical spine interbody fusion model was used to determine the effect of different cage design parameters (endplate-implant contact area, maximum contiguous pore) on interbody fusion. MATERIAL AND METHOD: IN VITRO EVALUATION: 24 sheep cadaver specimens (C2-C5) were tested in flexion, extension, axial rotation, and lateral bending with a nondestructive flexibility method using a nonconstrained testing apparatus. Four different groups were examined: (1) control group (intact) ( n=24), (2) autologous tricortical iliac crest bone graft ( n=8), (3) Harms cage ( n=8), and (4) SynCage-C ( n=8). IN VIVO EVALUATION: 24 sheep underwent C3/4 discectomy and fusion: group 1: autologous tricortical iliac crest bone graft ( n=8), group 2: Harms cage filled with autologous cancellous iliac crest bone grafts ( n=8), and group 3: SynCage-C filled with autologous cancellous iliac crest bone grafts ( n=8). Radiographic scans were performed pre- and postoperatively and after 1, 2, 4, 8, and 12 weeks, respectively. At the same time points, disc space height (DSH), height index (HI), intervertebral angle (IVA), and endplate angle (EA) were measured. After 12 weeks the animals were killed and fusion sites were evaluated using biomechanical testing in flexion, extension, axial rotation, and lateral bending. Additionally, histomorphological and histomorphometrical analyses were performed. RESULTS: Over a 12-week period the cage groups showed significantly higher values for DSH, HI, IVA, and EA compared to the bone graft. In vivo stiffness was significantly higher for the tricortical iliac crest bone graft and Harms cage than in vitro stiffness. However, there was no difference between in vitro and in vivo stiffness of the SynCage-C. Histomorphometrical evaluation showed a more progressed bone matrix formation in the Harms cage group than in both other groups. CONCLUSION: The parameter endplate-implant contact area was not able to determine subsidence of cages. In contrast, the maximum contiguous pore of a cage significantly correlates with interbody bone matrix formation inside the cage. Additionally, there was no correlation between in vitro and in vivo stiffness of interbody fusion cages. Therefore, biomechanical in vitro studies are not able to determine in vivo outcome of fusion cages. Animal experimental evaluations of interbody fusion cages are essential prior to clinical use.

Animals↗
PubMed2005

Structural and genetic bases of arterial stiffness.

Arterial stiffness has independent predictive value for cardiovascular events. We review data concerning the heritability of arterial stiffness, and propose an integrated view of the structural and genetic determinants of arterial stiffness, based on a candidate gene approach and recent studies on gene expression profile. Arterial stiffness seems to have a genetic component, which is largely independent of the influence of blood pressure and other cardiovascular risk factors. In animal models of essential hypertension (SHR and SHR-SP), structural modifications of the arterial wall include an increase in the number of elastin/smooth muscle cell (SMC) connections, and smaller fenestrations of the internal elastic lamina, possibly leading to redistribution of the mechanical load toward elastic materials. These modifications may give rise to mechanisms that explain why changes in arterial wall material accompanying wall hypertrophy in these animals are not associated with an increase in arterial stiffness. In monogenic connective tissue diseases (Marfan, Williams, and Ehlers-Danlos syndromes) and the corresponding animal models, precise characterization of the arterial phenotype makes it possible to determine the influence of abnormal genetically determined wall components on arterial stiffness. Such studies have highlighted the role of extracellular matrix signaling in the vascular wall and have shown that elastin and collagen not only display elasticity or rigidity but also are involved in the control of SMC function. These data provide strong evidence that arterial stiffness is affected by the amount and density of stiff wall material and the spatial organization of that material.

Animals↗
PubMed1997

Large artery stiffness in hypertension.

EFFECTS OF HYPERTENSION ON LARGE ARTERIES: The mechanical properties of large arteries make a major contribution to cardiovascular haemodynamics through the buffering of stroke volume and by propagation of the pressure pulse. A sustained increase in blood pressure often leads to stiffness of the large arteries, especially when other risk factors are present. The increased stiffness, in turn, aggravates hypertension by increasing systolic blood pressure and can induce cardiac hypertrophy and arterial lesions. Epidemiological studies strongly suggest that subjects with stiffer arteries have a high pulse pressure, and that stiffening of large arteries is associated with excess morbidity and mortality independently of other cardiovascular risk factors. ENVIRONMENTAL AND GENETIC FACTORS: Apart from high blood pressure and ageing, various environmental and genetic factors that influence the composition of the extracellular matrix of the arterial wall can increase arterial stiffness. Clinical studies suggest that the presence of some genotypes may be a particularly important risk marker for arterial stiffness, and may modulate the effects of hypertension, ageing and lipids on large arteries. EFFECTS OF ANTIHYPERTENSIVE DRUGS: The development of accurate, non-invasive methods has now made it possible to detect alterations of the large arteries. Among antihypertensive drugs, angiotensin converting enzyme inhibitors and calcium channel blockers have proved to be highly effective in improving large artery compliance, and have shown no adverse effects on metabolic factors that can alter arterial structure and function such as lipids, plasma glucose and insulin tolerance. Therefore these drugs may be particularly suitable for treating patients with increased arterial stiffness. Finally, a determination of genotypes may be helpful in the future in choosing antihypertensive therapy.

Adult↗
PubMed2004

Low-dose UVA1 phototherapy in systemic sclerosis: effects on acrosclerosis.

BACKGROUND: Increased collagen synthesis, vascular damage, and T-lymphocytic infiltration contribute to the development of systemic sclerosis. Preliminary studies revealed the effectiveness of low-dose UVA1 phototherapy in acrosclerosis. OBJECTIVE: We sought to confirm data of a pilot study revealing the efficacy of low-dose UVA1 irradiation in acrosclerosis in a larger number of patients. METHODS: Symptoms of 18 patients receiving low-dose UVA1 phototherapy were evaluated clinically and biometrically in an open, nonrandomized study. A number of pretherapeutic and posttherapeutic biopsy specimens were tested immunohistochemically for matrix-metalloproteinase-1. RESULTS: UVA1 irradiation led to softening of former stiffness reflected by a significant decrease of the hand score, increase of total skin distension, and reduction of skin thickness. Posttherapeutically, matrix-metalloproteinase-1 immunolabeling revealed a significant dermal elevation of collagenase. CONCLUSION: Low-dose UVA1 phototherapy is a capable treatment option for acrosclerosis. Its beneficial effect may be mediated by the induction of collagenases and a reduction of collagen deposition and cellular infiltration.

Adult↗
PubMed2004

Active and passive components in the length-dependent stiffness of tracheal smooth muscle during isotonic shortening.

Contraction of smooth muscle tissue involves interactions between active and passive structures within the cells and in the extracellular matrix. This study focused on a defined mechanical behavior (shortening-dependent stiffness) of canine tracheal smooth muscle tissues to evaluate active and passive contributions to tissue behavior. Two approaches were used. In one, mechanical measurements were made over a range of temperatures to identify those functions whose temperature sensitivity (Q(10)) identified them as either active or passive. Isotonic shortening velocity and rate of isometric force development had high Q(10) values (2.54 and 2.13, respectively); isometric stiffness showed Q(10) values near unity. The shape of the curve relating stiffness to isotonic shortening lengths was unchanged by temperature. In the other approach, muscle contractility was reduced by applying a sudden shortening step during the rise of isometric tension. Control contractions began with the muscle at the stepped length so that properties were measured over comparable length ranges. Under isometric conditions, redeveloped isometric force was reduced, but the ratio between force and stiffness did not change. Under isotonic conditions beginning during force redevelopment at the stepped length, initial shortening velocity and the extent of shortening were reduced, whereas the rate of relaxation was increased. The shape of the curve relating stiffness to isotonic shortening lengths was unchanged, despite the step-induced changes in muscle contractility. Both sets of findings were analyzed in the context of a quasi-structural model describing the shortening-dependent stiffness of lightly loaded tracheal muscle strips.

Animals↗
PubMed2003

Arterial remodeling and stiffness in patients with pseudoxanthoma elasticum.

OBJECTIVE: Proteoglycans organize the extracellular matrix, act as signaling molecules, and are involved in cell migration and proliferation. They may play an important role in arterial geometric and elastic properties. The aim of the present study was to determine large artery phenotype in patients with pseudoxanthoma elasticum (PXE), a genetic disease characterized by proteoglycan accumulation and fragmented elastic fibers in connective tissues. METHODS AND RESULTS: In 27 patients with PXE (25 females and 2 male) and 27 control subjects matched by age, sex, and blood pressure, we noninvasively determined the common carotid and radial artery diameter, intima-media thickness (IMT), and distensibility with high-definition echo-tracking systems and applanation tonometry. Patients with PXE had a significantly higher carotid IMT (611+/-106 versus 520+/-76 microm, P<0.001) independently of body surface area, age, and mean blood pressure. The increase in carotid IMT predominated in older patients with PXE at the time of examination. No significant difference in carotid elastic properties was observed between patients with PXE and control subjects. At the site of the radial artery, distensibility was significantly higher in patients with PXE than in control subjects (11.6+/-11.4 versus 5.9+/-3.4 kPa(-1) x 0.10(-3); P=0.02) and internal diameter was lower (1.66+/-0.51 versus 2.07+/-0.36 mm; P<0.01) without change in intima-media thickness and Young's elastic modulus. CONCLUSIONS: Phenotypic changes of superficial arteries in patients with PXE were represented by a thickening of the carotid artery and a reduced stiffness of the radial artery and predominated in older female patients.

Adult↗
PubMed2003

Matrix metalloproteinase inhibition modifies left ventricular remodeling after myocardial infarction in pigs.

BACKGROUND: Global and regional shape changes that occur within the left ventricular wall after myocardial infarction have been termed infarct expansion. A potential mechanism for this postinfarction remodeling is activation of the matrix metalloproteinases. Accordingly, the present study examined the effects of matrix metalloproteinase inhibition on left ventricular global geometry after myocardial infarction in pigs. METHODS: Myocardial infarction was created in pigs by means of occlusion of the first and second obtuse marginal branches of the circumflex coronary artery, resulting in a uniform left ventricular free wall infarct size of 21% +/- 2%. At 5 days after infarction, the pigs were randomized to undergo broad-spectrum matrix metalloproteinase inhibition (n = 9; PD166793, 20 mg. kg(-1). d(-1) by mouth) or myocardial infarction alone (n = 8). Ten pigs served as noninfarction control animals. Left ventricular end-diastolic area, determined by means of echocardiography, was measured 8 weeks after infarction. RESULTS: Left ventricular end-diastolic area increased in both the myocardial infarction plus broad-spectrum matrix metalloproteinase inhibition and myocardial infarction only groups compared to reference control animals (3.7 +/- 0.2 cm(2)), but was reduced with broad-spectrum matrix metalloproteinase inhibition compared to myocardial infarction alone (4.5 +/- 0.2 vs 4.9 +/- 0.2 cm(2), respectively; P <.05). Regional radial stress within the infarct region increased in both infarction groups when compared to values obtained from reference control animals (599 +/- 152 g/cm(2)), but was attenuated in the myocardial infarction plus broad-spectrum matrix metalloproteinase inhibition group compared to the myocardial infarction alone group (663 +/- 108 vs 1242 +/- 251 g/cm(2), respectively; P <.05). Similarly, regional myocardial stiffness increased in both the myocardial infarction plus broad-spectrum matrix metalloproteinase inhibition and the myocardial infarction only groups compared with that observed in reference control animals (14 +/- 1 rkm, P <.05) but was lower with broad-spectrum matrix metalloproteinase inhibition than with myocardial infarction alone (42 +/- 6 vs 68 +/- 10 rkm, respectively; P <.05). CONCLUSIONS: Matrix metalloproteinase inhibition reduced postinfarction left ventricular dilation, reduced regional myocardial wall stress, and modified myocardial material properties. These unique findings suggest that increased myocardial matrix metalloproteinase activation after infarction contributes directly to the left ventricular remodeling process.

Analysis of Variance↗
PubMed1969

Elastic coefficients of animal bone.

The elastic stiffness coefficients of dried bovine phalanx and femur and of fresh bovine phalanx were measured by an ultrasonic technique. An analysis of the crystallographic structure of the principal components of bone and its piezoelectric and pyroelectric behavior showed that bone is a texture that has the same elastic coeffcient matrix as a hexagonal single crystal. The five elastic stiffness coefficients of fresh phalanx are: C(1l), 1.97; C(12), 1.21; C(13), 1.26; C(33), 3.20; and C(44), 0.54 (all in units of 10(11) dynes per square centimeter). Value of axial and transverse Young's and shear moduli, compressibility, and the three Poisson's ratios were calculated.

Animals↗
PubMed2005

Matrix concentration of insulin-like growth factor I (IGF-I) is negatively associated with biomechanical properties of human tibial cancellous bone within individual subjects.

Insulin-like growth factor-I (IGF-I), abundant in bone matrix, is believed to play an important role during bone development and remodeling. To our knowledge, however, few studies have addressed the relationship between the concentration of IGF-I in bone matrix and the biomechanical properties of bone tissue. In this study, forty-five cylindrical specimens of cancellous bone were harvested from six human tibiae and scanned using micro-computed tomography (microCT). The bone volume fraction (BV/TV) was calculated from three-dimensional (3D) microCT images. Mechanical tests were then performed on a servohydraulic testing system to determine the strength and stiffness of cancellous bone. Following mechanical testing, the concentration of IGF-I in bone matrix was measured by using an enzyme-linked immunoabsorbent assay (ELISA). Within each subject, the concentration of IGF-I in bone matrix had significant (P<0.01) negative correlations with the bone volume fraction, strength, and stiffness of cancellous bone. In particular, the anterior quadrant of the proximal tibia was significantly (P<0.02) greater in IGF-I matrix concentration and marginally significantly lower in strength (P=0.053) and stiffness (P=0.059) than the posterior quadrant. The negative correlations between the cancellous bone matrix concentration of IGF-I and cancellous bone biomechanical properties within subjects found in this study may help us understand the variation of the biomechanical properties of cancellous bone in proximal human tibiae.

Biomechanical Phenomena↗
PubMed2003

Mechanotransduction and flow across the endothelial glycocalyx.

In this inaugural paper, we shall provide an overview of the endothelial surface layer or glycocalyx in several roles: as a transport barrier, as a porous hydrodynamic interface in the motion of red and white cells in microvessels, and as a mechanotransducer of fluid shearing stresses to the actin cortical cytoskeleton of the endothelial cell. These functions will be examined from a new perspective, the quasiperiodic ultrastructural model proposed in Squire et al. [Squire, J. M., Chew, M., Nneji, G., Neal, C., Barry, J. & Michel, C. (2001) J. Struct. Biol. 136, 239-255] for the 3D organization of the endothelial surface layer and its linkage to the submembranous scaffold. We shall show that the core proteins in the bush-like structures comprising the matrix have a flexural rigidity, EI, that is sufficiently stiff to serve as a molecular filter for plasma proteins and as an exquisitely designed transducer of fluid shearing stresses. However, EI is inadequate to prevent the buckling of these protein structures during the intermittent motion of red cells or the penetration of white cell microvilli. In these cellular interactions, the viscous draining resistance of the matrix is essential for preventing adhesive molecular interactions between proteins in the endothelial membrane and circulating cellular components.

Actins↗
PubMed2002

Cardiac fibrosis as a cause of diastolic dysfunction.

BACKGROUND: Diastolic dysfunction is increasingly recognized as a cause of symptomatic heart failure, including the clinical syndrome congestive heart failure (CHF). Meta-analyses of earlier studies of this disorder suggest 40-50% of patients with congestive heart failure have preserved left ventricular systolic function. Conditions associated with diastolic dysfunction are diverse and most commonly include ischemic cardiomyopathy with previous myocardial infarction(s) and hypertensive heart disease. PATHOPHYSIOLOGY: An underlying histopathologic finding in each of these entities is an adverse accumulation and structural remodeling of the heart's fibrillar collagen matrix expressed as cardiac fibrosis. In ventricular tissue fibrosis serves to impose a viscoelastic burden that compromises all of diastole, including the rate of relaxation, diastolic suction and passive stiffness. Various factors contribute to the abnormal accumulation of this fibrillar matrix. Of particular importance are effector hormones of the renin-angiotensin-aldosterone system. TREATMENT: In experimental studies, pharmacologic interference with each of these circulating hormones, either through ACE inhibition or respective receptor antagonism, proves cardioprotective by preventing fibrosis while preserving diastolic function. Additionally, a regression of established cardiac fibrosis by its presumptive proteolytic digestion induced by ACE inhibition or AT receptor antagonism has been demonstrated. This cardioreparative strategy improves tissue stiffness and suggests diastolic dysfunction is reversible.

Diastole↗