This project continues the theme of relating the behavior of the whole left ventricle to its constituent cardiac muscle fibers. Two distinct topics have been targeted. The first asks: How similar (or different) are the amounts of shortening and end-systolic segment lengths of muscle fibers in various layers (transmurally) or regions of the left ventricle? The more homogeneous the distribution, the more the behavior of the whole ventricle will correspond to that of its muscle fibers (after transforming for geometry). However, in a heterogeneous population, alterations in the distribution as chamber volume increases (by recruitment of short sub-endocardial fibers, for example) would provide another mechanism for the Frank-Starling law of the heart. To study the patterns of segment lengths and shortening in the beating heart, we will combine radiological and histological approaches. Small beads inserted into canine myocardium will be tracked via biplane cineradiography and an automated marker- locating system. The patterns of strain in several myocardial layers will be observed throughout the cardiac cycle in isolated canine hearts, while simultaneously monitoring and controlling ventricular pressure and volume. The second topic explores implications of the delayed-force property of myocardium. While well acknowledged as a fundamental property of striated myofilaments, the implications of delayed force for cardiac mechanics have never been fully considered. Recent ventricular studies by this laboratory suggest that it plays an important role in determining end-systolic pressure. Possibly, by retaining later into systole some of the force-generating potential developed at the initial stretched length, delayed force could provide a mechanism to oppose the deactivating effects of shortening. Hence, the physiologic basis for end-systolic pressure-volume relations may rest partially on a balance between these opposing effects -- a balance that might be disturbed by disease. Since this is such a fundamental question, it will be investigated initially in excised papillary muscles. To avoid end artifacts, a healthy central segment of the muscle will be defined by inserting two pins into the muscle and tracking their locations electro-optically. Predicted effects of delayed force (such as more end-systolic force with moderate shortening than in isometric contraction, history-dependent variations in force-velocity relations, etc.) will be tested. Moreover, we will examine whether these effects alter as predicted by the delayed force concept when the time-course of contraction is changed.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL030552-06
Application #
3341570
Study Section
Experimental Cardiovascular Sciences Study Section (ECS)
Project Start
1983-07-01
Project End
1991-03-31
Budget Start
1990-04-01
Budget End
1991-03-31
Support Year
6
Fiscal Year
1990
Total Cost
Indirect Cost
Name
Johns Hopkins University
Department
Type
Schools of Medicine
DUNS #
045911138
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Criscione, John C; Sacks, Michael S; Hunter, William C (2003) Experimentally tractable, pseudo-elastic constitutive law for biomembranes: I. Theory. J Biomech Eng 125:94-9
Criscione, John C; Sacks, Michael S; Hunter, William C (2003) Experimentally tractable, pseudo-elastic constitutive law for biomembranes: II. Application. J Biomech Eng 125:100-5
Criscione, J C; Lorenzen-Schmidt, I; Humphrey, J D et al. (1999) Mechanical contribution of endocardium during finite extension and torsion experiments on papillary muscles. Ann Biomed Eng 27:123-30
Rice, J J; Winslow, R L; Hunter, W C (1999) Comparison of putative cooperative mechanisms in cardiac muscle: length dependence and dynamic responses. Am J Physiol 276:H1734-54
Guccione, J M; Le Prell, G S; de Tombe, P P et al. (1997) Measurements of active myocardial tension under a wide range of physiological loading conditions. J Biomech 30:189-92
Guccione, J M; O'Dell, W G; McCulloch, A D et al. (1997) Anterior and posterior left ventricular sarcomere lengths behave similarly during ejection. Am J Physiol 272:H469-77
Janssen, P M; Hunter, W C (1995) Force, not sarcomere length, correlates with prolongation of isosarcometric contraction. Am J Physiol 269:H676-85
Campbell, K B; Taheri, H; Kirkpatrick, R D et al. (1993) Similarities between dynamic elastance of left ventricular chamber and papillary muscle of rabbit heart. Am J Physiol 264:H1926-41
Rodriguez, E K; Hunter, W C; Royce, M J et al. (1992) A method to reconstruct myocardial sarcomere lengths and orientations at transmural sites in beating canine hearts. Am J Physiol 263:H293-306
Humphrey, J D; Barazotto Jr, R L; Hunter, W C (1992) Finite extension and torsion of papillary muscles: a theoretical framework. J Biomech 25:541-7

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