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(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

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