During the cardiac cycle up to 70% of the end diastolic volume of blood is ejected with each stroke. As the contraction and subsequent recoil occur, the muscular walls undergo profound changes in shape characterized by variations in wall thickness and volume-filling by shortened, thickened papillary muscles and infoldings of the walls. These effects are accompanied by large changes in ventricular stiffness, with a diastolic to systolic compliance ratio of 50 to 1. Extremely rapid filling during the initial phase of diastolic recoil then occurs without the benefit of any antagonistic muscles. This striking range of dynamic versatility is produced by the geometrical interplay of a large population of variously oriented muscle cells that undergo cyclical relative motions. The rapid and continuous relative sliding of heart muscle cells implies that they must be interconnected in a precise manner, with constraints on extreme displacements. Return to diastolic configuration is rapid and must be promoted by release of energy elastically stored during systole. Furthermore, the maintenance of patency of the myocytes throughout many contractile cycles and the efficiency of transduction of energy to the motion of cells depends critically on the viscosity, and thus on the level of hydration of the extracellular matrix. We propose to further develop and apply specific methods for visualizing and identifying connective tissue structures in heart muscle by means of antibody stains and histological stains for light microscopy and scanning, transmission, and high voltage transmission E.M. We will determine the dispositions of extracellular substances relative to myocytes, in various regions of the heart, for elastin, microfibrils, collagen types, fibronectin, and laminin. Our goals also include the determination of changes in orientation of large collagen and elastin fibers in isolated heart muscles in states of stretch and contraction relative to relaxed state in correlated structural-mechanical studies. The roles of connective tissue relative to myocytes in elastic recoil will be explored in correlated structural-kinematic studies of muscles and enzymatically isolated myocytes. Several models are proposed as working hypotheses to aid in organizing information, designing experiments, and interpreting and evaluating results.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
2R01HL024336-07
Application #
3337601
Study Section
Cardiovascular Study Section (CVA)
Project Start
1979-09-01
Project End
1989-03-31
Budget Start
1986-04-01
Budget End
1987-03-31
Support Year
7
Fiscal Year
1986
Total Cost
Indirect Cost
Name
Albert Einstein College of Medicine
Department
Type
Schools of Medicine
DUNS #
009095365
City
Bronx
State
NY
Country
United States
Zip Code
10461
Eghbali, M; Eghbali, M; Robinson, T F et al. (1989) Collagen accumulation in heart ventricles as a function of growth and aging. Cardiovasc Res 23:723-9
Eghbali, M; Blumenfeld, O O; Seifter, S et al. (1989) Localization of types I, III and IV collagen mRNAs in rat heart cells by in situ hybridization. J Mol Cell Cardiol 21:103-13
Eghbali, M; Silman, I; Robinson, T F et al. (1988) Visualization of collagenase-sensitive acetylcholinesterase in isolated cardiomyocytes and in heart tissue. Cell Tissue Res 253:281-6
Factor, S M; Robinson, T F (1988) Comparative connective tissue structure-function relationships in biologic pumps. Lab Invest 58:150-6
Dickson, C P; Robinson, T F (1988) Differentiating cardiac elastin, collagen and microfibrils with NaOH at the ultrastructural level. Histochemistry 89:105-7
Robinson, T F; Geraci, M A; Sonnenblick, E H et al. (1988) Coiled perimysial fibers of papillary muscle in rat heart: morphology, distribution, and changes in configuration. Circ Res 63:577-92
Robinson, T F; Cohen-Gould, L; Factor, S M et al. (1988) Structure and function of connective tissue in cardiac muscle: collagen types I and III in endomysial struts and pericellular fibers. Scanning Microsc 2:1005-15
Elias, L; Van Epps, D E; Smith, K J et al. (1987) A trial of recombinant alpha 2 interferon in the myelodysplastic syndrome: II. Characterization and response of granulocyte and platelet dysfunction. Leukemia 1:111-5
Robinson, T F; Factor, S M; Capasso, J M et al. (1987) Morphology, composition, and function of struts between cardiac myocytes of rat and hamster. Cell Tissue Res 249:247-55
Factor, S M; Robinson, T F; Dominitz, R et al. (1987) Alterations of the myocardial skeletal framework in acute myocardial infarction with and without ventricular rupture. A preliminary report. Am J Cardiovasc Pathol 1:91-7

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