This Article Full Text Full Text (PDF) Data Supplement Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Weis, S. M. Articles by McCulloch, A. D. Search for Related Content PubMed PubMed Citation Articles by Weis, S. M. Articles by McCulloch, A. D. Related Collections Remodeling Animal models of human disease Genetically altered mice

(Circulation Research. 2000;87:663.)
© 2000 American Heart Association, Inc.

Integrative Physiology

Myocardial Mechanics and Collagen Structure in the Osteogenesis Imperfecta Murine (oim)

Sara M. Weis, Jeffrey L. Emery, K. David Becker, Daniel J. McBride, Jr, Jeffrey H. Omens, Andrew D. McCulloch

From the Departments of Bioengineering (S.M.W., J.L.E., J.H.O., A.D.M.) and School of Medicine (K.D.B., J.H.O.), University of California, San Diego, La Jolla, Calif, and Division of Geriatric Medicine and Gerontology (D.J.M.), Johns Hopkins School of Medicine, Baltimore, Md.

Correspondence to Andrew D. McCulloch, PhD, University of California, San Diego, Department of Bioengineering, 9500 Gilman Dr, La Jolla, CA 92093-0412. E-mail amcculloch{at}ucsd.edu

Abstract—Because the amount and structure of type I collagen are thought to affect the mechanics of ventricular myocardium, we investigated myocardial collagen structure and passive mechanical function in the osteogenesis imperfecta murine (oim) model of pro-2(I) collagen deficiency, previously shown to have less collagen and impaired biomechanics in tendon and bone. Compared with wild-type littermates, homozygous oim hearts exhibited 35% lower collagen area fraction (P<0.05), 38% lower collagen fiber number density (P<0.05), and 42% smaller collagen fiber diameter (P<0.05). Compared with wild-type, oim left ventricular (LV) collagen concentration was 45% lower (P<0.0001) and nonreducible pyridinoline cross-link concentration was 22% higher (P<0.03). Mean LV volume during passive inflation from 0 to 30 mm Hg in isolated hearts was 1.4-fold larger for oim than wild-type (P=NS). Uniaxial stress-strain relations in resting right ventricular papillary muscles exhibited 60% greater strains (P<0.01), 90% higher compliance (P=0.05), and 64% higher nonlinearity (P<0.05) in oim. Mean opening angle, after relief of residual stresses in resting LV myocardium, was 121±9 degrees in oim compared with 45±4 degrees in wild-type (P<0.0001). Mean myofiber angle in oim was 23±8 degrees greater than wild-type (P<0.02). Decreased myocardial collagen diameter and amount in oim is associated with significantly decreased fiber and chamber stiffness despite modestly increased collagen cross-linking. Altered myofiber angles and residual stress may be beneficial adaptations to these mechanical alterations to maintain uniformity of transmural fiber strain. In addition to supporting and organizing myocytes, myocardial collagen contributes directly to ventricular stiffness at high and low loads and can influence stress-free state and myofiber architecture.

Key Words: heart • ventricle • collagen • stiffness • residual stress

This article has been cited by other articles:

				D. J. Marsh, I. Toma, O. V. Sosnovtseva, J. Peti-Peterdi, and N.-H. Holstein-Rathlou Electrotonic vascular signal conduction and nephron synchronization Am J Physiol Renal Physiol, April 1, 2009; 296(4): F751 - F761. [Abstract] [Full Text] [PDF]

				A. Cheng, T. C. Nguyen, M. Malinowski, G. T. Daughters, D. C. Miller, and N. B. Ingels Jr Heterogeneity of Left Ventricular Wall Thickening Mechanisms Circulation, August 12, 2008; 118(7): 713 - 721. [Abstract] [Full Text] [PDF]

				A. Oganesian, S. Au, J. A. Horst, L. C. Holzhausen, A. J. Macy, J. M. Pace, and P. Bornstein The NH2-terminal Propeptide of Type I Procollagen Acts Intracellularly to Modulate Cell Function J. Biol. Chem., December 15, 2006; 281(50): 38507 - 38518. [Abstract] [Full Text] [PDF]

				G. Ertl and S. Frantz Healing after myocardial infarction Cardiovasc Res, April 1, 2005; 66(1): 22 - 32. [Abstract] [Full Text] [PDF]

				K. B. Harrington, F. Rodriguez, A. Cheng, F. Langer, H. Ashikaga, G. T. Daughters, J. C. Criscione, N. B. Ingels, and D. C. Miller Direct measurement of transmural laminar architecture in the anterolateral wall of the ovine left ventricle: new implications for wall thickening mechanics Am J Physiol Heart Circ Physiol, March 1, 2005; 288(3): H1324 - H1330. [Abstract] [Full Text] [PDF]

				J. C. Walker, J. M. Guccione, Y. Jiang, P. Zhang, A. W. Wallace, E. W. Hsu, and M. B. Ratcliffe Helical myofiber orientation after myocardial infarction and left ventricular surgical restoration in sheep J. Thorac. Cardiovasc. Surg., February 1, 2005; 129(2): 382 - 390. [Abstract] [Full Text] [PDF]

				M. A. Sussman, A. McCulloch, and T. K. Borg Dance Band on the Titanic: Biomechanical Signaling in Cardiac Hypertrophy Circ. Res., November 15, 2002; 91(10): 888 - 898. [Abstract] [Full Text] [PDF]

				J. M.B. Anumonwo, Y. N. Tallini, F. J. Vetter, and J. Jalife Action Potential Characteristics and Arrhythmogenic Properties of the Cardiac Conduction System of the Murine Heart Circ. Res., August 17, 2001; 89(4): 329 - 335. [Abstract] [Full Text] [PDF]