Myocardial mechanics and collagen structure in the osteogenesis imperfectamurine (oim)

Because the amount and structure of type I collagen are thought to affect t he mechanics of ventricular myocardium, we investigated myocardial collagen structure and passive mechanical function in the osteogenesis imperfecta m urine (oim) model of pro-alpha2(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 colla gen 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-typ e, 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 isolat ed hearts was 1.4-fold larger for oim than wild-type (P=NS), Uniaxial stres s-strain relations in resting right ventricular papillary muscles exhibited 60% greater strains (P<0.01), 90% higher compliance (P=0.05), and 64% high er nonlinearity (P<0.05) in oim. Mean opening angle, after relief of residu al stresses in resting LV myocardium, was 121+/-9 degrees in oim compared w ith 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 collag en diameter and amount in oim is associated with significantly decreased fi ber 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 coll agen contributes directly to ventricular stiffness at high and low loads an d can influence stress-free state and myofiber architecture.