Reza Mazhari

Bio: Reza Mazhari is an academic researcher from University of California, San Diego. The author has contributed to research in topics: Myocardial stunning & CXL 1020. The author has an hindex of 7, co-authored 10 publications receiving 445 citations.

Effect of Laminar Orthotropic Myofiber Architecture on Regional Stress and Strain in the Canine Left Ventricle

Abstract: Recent morphological studies have demonstrated a laminar (sheet) organization of ventricular myofibers. Multiaxial measurements of orthotropic myocardial constitutive properties have not been reported, but regional distributions of three-dimensional diastolic and systolic strains relative to fiber and sheet axes have recently been measured in the dog heart by Takayama et al. [30]. A three-dimensional finite-deformation, finite element model was used to investigate the effects of material orthotropy on regional mechanics in the canine left ventricular wall at end-diastole and end-systole. The prolate spheroidal model incorporated measured transmural distributions of fiber and sheet angles at the base and apex. Compared with transverse isotropy, the orthotropic model of passive myocardial properties yielded improved agreement with measured end-diastolic strains when: (1) normal stiffness transverse to the muscle fibers was increased tangent to the sheets and decreased normal to them; (2) shear coefficients were increased within sheet planes and decreased transverse to them. For end-systole, orthotropic passive properties had little effect, but three-dimensional systolic shear strain distributions were more accurately predicted by a model in which significant active systolic stresses were developed in directions transverse to the mean fiber axis as well as axial to them. Thus the ventricular laminar architecture may give rise to anisotropic material properties transverse to the fibers with greater resting stiffness within than between myocardial laminae. There is also evidence that intact ventricular muscle develops significant transverse stress during systole, though it remains to be seen if active stress is also orthotropic with respect to the laminar architecture.

Structural basis of regional dysfunction in acutely ischemic myocardium

Abstract: Objective: Impaired systolic function in the normally perfused myocardium adjacent to an ischemic region — the functional border zone — is thought to result from mechanical interactions across the perfusion boundary. We investigated how segment orientation and vessel involved affect regional strains in the functional border zone and whether altered stresses associated with a step transition in contractility can explain the functional border zone. Methods and results: Regional epicardial strain distributions were obtained from measured displacements of radiopaque markers in open-chest anesthetized canines, and related to local myofiber angles and blood flows. The functional border zone for fiber strain was significantly narrower than that for cross-fiber strain and significantly wider for left anterior descending (LAD) than left circumflex (LCx) coronary occlusion (1.23 vs. 0.45 cm). A detailed three-dimensional computational model with a one-to-one relation between perfusion and myofilament activation and no transitional zone of intermediate contractility showed close agreement with these observations and significantly elevated stresses in the border zone. Differences between LAD and LCx occlusions in the model were due to differences in left ventricular systolic pressure and not to differences in perfusion boundary or muscle fiber orientation. The border zone was narrower for fiber strain than cross-fiber strain because systolic stiffness is greatest along the muscle fiber direction. Conclusion: Abnormal regional mechanics in the acute ischemic border arise from increased wall stresses without a transitional zone of intermediate contractility. Perfusion is more tightly coupled to fiber than cross-fiber strain, and a wider functional border zone of fiber strain during LAD than LCx occlusion is primarily due to higher regional wall stresses rather than anatomic variations.

Transmural Distribution of Three-Dimensional Systolic Strains in Stunned Myocardium

Abstract: Background Regional function in stunned myocardium is usually thought to be more depressed in the endocardium than the epicardium. This has been attributed to the greater loss of blood flow at the endocardium during ischemia. Methods and Results We measured transmural distributions of 3D systolic strains relative to local myofiber axes in open-chest anesthetized dogs before 15 minutes of left anterior descending coronary artery occlusion and during 2 hours of reperfusion. During ischemia, regional myocardial blood flow was reduced 84% at the endocardium and 32% at the epicardium (P<0.005, n=7), but changes in end-systolic fiber length from baseline were transmurally uniform. Relative to baseline, radial segments in stunned tissue were significantly thinner at the endocardium than the epicardium at end systole (24±5% versus 16±3%; P<0.05, n=8), consistent with previous reports. Unlike radial and cross-fiber segments, however, the increase of end-systolic fiber lengths in stunned myocardium had no significa...

Regional myocardial perfusion and mechanics: a model-based method of analysis.

Abstract: A new parametric model-based method has been developed that allows epicardial strain distributions to be computed on the left ventricular free wall in normal and ischemic myocardium and integrated with the regional distributions of anatomic and physiological measurements so that underlying relationships can be explored. An array of radiopaque markers was sewn on the anterior wall of the left ventricle (LV) in three anesthetized open-chest canines, and their positions were recorded using biplane video fluoroscopy before and 2 min after occlusion of the left anterior descending coronary artery. The three-dimensional (3D) anatomy of the LV and epicardial fiber angles were measured post-mortem using a 3D probe. A prolate spheroidal finite element model was fitted to the epicardial surface points (with <0.2 mm accuracy) and fiber angles (<5 degrees error). Regional myocardial blood flows (MBFs) were measured using fluorescent microspheres and fitted into the model (<0.3 ml min(-1) g(-1) error). Epicardial fiber and cross-fiber strain distributions were computed by allowing the model to deform from end-diastole to end-systole according to the recorded motion of the surface markers. Systolic fiber strain varied from -0.05 to 0.01 within the region of the markers during baseline, and regional MBF varied from 1.5 to 2.0 ml min(-1) g(-1). During 2 min ischemia, regional MBF was less than 0.3 ml min(-1) g(-1) in the ischemic region and 1.0 ml min(-1) g(-1) in the nonischemic region, and fiber strain ranged from 0.05 in the central ischemic zone to -0.025 in the remote nonischemic tissue. This analysis revealed a zone of impaired fiber shortening extending into the normally perfused myocardium that was significantly wider at the base than the apex. A validation analysis showed that a regularizing function can be optimized to minimize both fitting errors and numerical oscillations in the computed strain fields.

Integrative models for understanding the structural basis of regional mechanical dysfunction in ischemic myocardium.

Abstract: Myocardial ischemia and many other cardiac pathologies are associated with regional ventricular dysfunction. Since the distributions of stress and material properties cannot be measured directly in intact myocardium, understanding how regional alterations in myocardial strain or segment function are related to underlying cellular dysfunction must be deduced from theoretical models. Here, we describe how anatomically detailed, three-dimensional computational models can be used in conjunction with experimental or clinical studies to elucidate the structural basis of regional dysfunction in acutely ischemic and ischemic-reperfused (“stunned”) myocardium in vivo. Integrative experimental and computational analysis shows that: (1) in acutely ischemic myocardium, the transition from abnormal systolic strain in the ischemic region to normal shortening in adjacent, normally perfused tissue is governed primarily by systolic blood pressure and regional fiber orientation rather than the geometry of the perfusion boundary; and (2) in stunned myocardium, the degree of reperfusion injury to the contractile apparatus may be uniform across the wall thickness despite observations that the extent of ischemia and the impairment of regional strain during reperfusion are both significantly greater in the subendocardium. © 2000 Biomedical Engineering Society. PAC00: 8719Hh, 8719Uv, 8719Ff, 8719Rr, 8710+e

Prevention of myocardial infarction induced ventricular expansion and remodeling

Abstract: A method for direct therapeutic treatment of myocardial tissue in a localized region of a heart having a pathological condition. The method includes identifying a target region of the myocardium and applying material directly and substantially only to at least a portion of the myocardial tissue of the target region. The material applied results in a physically modification the mechanical properties, including stiffness, of said tissue. Various devices and modes of practicing the method are disclosed for stiffening, restraining and constraining myocardial tissue for the treatment of conditions including myocardial infarction or mitral valve regurgitation.

Computational Mechanics of the Heart

Abstract: Finite elasticity theory combined with finite element analysis provides the framework for analysing ventricular mechanics during the filling phase of the cardiac cycle, when cardiac cells are not actively contracting. The orthotropic properties of the passive tissue are described here by a “pole–zero” constitutive law, whose parameters are derived in part from a model of the underlying distributions of collagen fibres. These distributions are based on our observations of the fibrous-sheet laminar architecture of myocardial tissue. We illustrate the use of high order (cubic Hermite) basis functions in solving the Galerkin finite element stress equilibrium equations based on this orthotropic constitutive law and for incorporating the observed regional distributions of fibre and sheet orientations. Pressure–volume relations and 3D principal strains predicted by the model are compared with experimental observations. A model of active tissue properties, based on isolated muscle experiments, is also introduced in order to predict transmural distributions of 3D principal strains at the end of the contraction phase of the cardiac cycle. We end by offering a critique of the current model of ventricular mechanics and propose new challenges for future modellers.

Protein Nitration in Cardiovascular Diseases

Abstract: There is growing evidence that cardiovascular disease is associated with progressive changes in the production of free radicals and radical-derived reactive species. These intermediates react with all major cellular constituents and may serve several physiological and pathophysiological functions. The nitration of protein tyrosine residues has been used as a footprint for in vivo production of radical and nonradical reactive species. Tyrosine nitration may alter protein function and metabolism and therefore, provides for further dysfunctional changes. This review focuses on an appearance of tyrosine nitrated proteins in cardiovascular tissues under different settings of cardiovascular disease. Sources of reactive species, putative mechanisms of protein nitration in vivo, as well as protein nitration under normal physiological conditions, are also described. The goal of this review is to attract more attention to identification of specific proteins, which undergo tyrosine nitration and to study a correlation between their altered function and pathology. Understanding how protein nitration affects disease progression may offer a unique option for design of antioxidant therapy for the treatment of cardiovascular complications. At the same time, protein nitration can be a biological marker of efficiency of antioxidant therapy.

Structure and Mechanics of Healing Myocardial Infarcts

Abstract: Therapies for myocardial infarction have historically been developed by trial and error, rather than from an understanding of the structure and function of the healing infarct. With exciting new bioengineering therapies for myocardial infarction on the horizon, we have reviewed the time course of structural and mechanical changes in the healing infarct in an attempt to identify key structural determinants of mechanics at several stages of healing. Based on temporal correlation, we hypothesize that normal passive material properties dominate the mechanics during acute ischemia, edema during the subsequent necrotic phase, large collagen fiber structure during the fibrotic phase, and cross-linking of collagen during the long-term remodeling phase. We hope these hypotheses will stimulate further research on infarct mechanics, particularly studies that integrate material testing, in vivo mechanics, and quantitative structural analysis.