The long-range goal is to understand the adult myofiber pattern in the human heart and its morphogenesis and to relate this understanding to the contractile and conductive properties of the heart. The work builds on our experience gained in reconstructing the global myofiber patter.
Specific aims are to : a) establish the myofibre pattern in the fetal, neonatal and adult heart; b) establish the pattern in the embryonic, neonatal and adult heart and c) to build a mathematical model of myofiber morphogenesis in hearts. In addition the myofiber pattern in asymmetric septal hypertrophy (where the normal pattern is know to be disrupted) will be studied in infant and adult hearts. The basic methodology utilizes embedding of whole hearts, emplacement of fiducials, serial sectioning, semiautomated photomicrography, manual digitization, automatic coordinate reassembly, interactive 3-D computer graphics reconstructions, graphics file editing, image production and archiving. Software to support interactive morphometrics on the 3-D displays is to be implemented in the near future. The basic methodology just summarized is varied to suit the size of the heart. Small hearts are embedded in toto, sectioned and submitted to 3-D reconstruction. Large hearts are serially sectioned at 1 or 2 nm on a macrovibratome or 'minitome' and photographed to produce macroscopic reconstructions. Small tissue samples are then excised systematically from individual tissue slices, embedded, sectioned in toto and submitted to 3- D reconstruction. In this way the myofiber pattern is reconstructed systematically in large or small hearts. The application of this methodology will lead to the first global description of the myofiber pattern and its morphogenesis in the mammalian heart The results will improve our understanding of the architecture of the normal hart and of certain cardiac abnormalities.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL029761-09
Application #
3340838
Study Section
Cardiovascular and Pulmonary Research A Study Section (CVA)
Project Start
1989-01-01
Project End
1992-12-31
Budget Start
1991-01-01
Budget End
1992-12-31
Support Year
9
Fiscal Year
1991
Total Cost
Indirect Cost
Name
University of Washington
Department
Type
Schools of Medicine
DUNS #
135646524
City
Seattle
State
WA
Country
United States
Zip Code
98195
McLean, M; Prothero, J (1992) Determination of relative fiber orientation in heart muscle: methodological problems. Anat Rec 232:459-65
McLean, M; Prothero, J W (1991) Three-dimensional reconstruction from serial sections. V. Calibration of dimensional changes incurred during tissue preparation and data processing. Anal Quant Cytol Histol 13:269-78
McLean, M; Prothero, J (1991) Myofiber orientation in the weanling mouse heart. Am J Anat 192:425-41
McLean, M; Ross, M A; Prothero, J (1989) Three-dimensional reconstruction of the myofiber pattern in the fetal and neonatal mouse heart. Anat Rec 224:392-406
Stimac, G K; Sundsten, J W; Prothero, J S et al. (1988) Three-dimensional contour surfacing of the skull, face, and brain from CT and MR images and from anatomic sections. AJR Am J Roentgenol 151:807-10
McLean, M R; Prothero, J (1987) Coordinated three-dimensional reconstruction from serial sections at macroscopic and microscopic levels of resolution: the human heart. Anat Rec 219:374-7, 434-9
Prothero, J (1986) Methodological aspects of scaling in biology. J Theor Biol 118:259-86
Prothero, J (1986) Scaling of energy metabolism in unicellular organisms: a re-analysis. Comp Biochem Physiol A Comp Physiol 83:243-8
Prothero, J S; Prothero, J W (1986) Three-dimensional reconstruction from serial sections. IV. The reassembly problem. Comput Biomed Res 19:361-73
Prothero, J S; Riggins, M; Lindsay, A et al. (1985) Three-dimensional reconstruction from serial sections III. AUTOSCAN, a software package in FORTRAN for semiautomated photomicrography. Comput Biomed Res 18:132-6

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