This study tested the hypothesis that with
hypertrophy, the proportion, distribution, and structural alignment of
fibrillar collagen are important determinants of myocardial stiffness. Toward this end, the
collagen volume fraction (morphometry), the transmural or subendocardial distribution of
collagen, and the structural arrangement of
fibrillar collagens (
picrosirius red) were examined in the hypertrophied ventricle secondary to pressure overload (abdominal aorta banding or
perinephritis),
isoproterenol, and pressure overload plus
isoproterenol. In the same hearts, the slopes of the systolic and diastolic stress-strain relations of the left ventricle, representing its active and passive stiffness, respectively, were obtained. In comparison with controls, we found 1) for a moderate rise in transmural
collagen, active and passive stiffness increased with pressure-overload
hypertrophy; 2) following
isoproterenol alone there was a marked increase in subendocardial
collagen, and active and passive stiffness increased; 3) in pressure-overload
hypertrophy plus
isoproterenol, active stiffness declined. Passive stiffness was increased except when
fibrosis and thinning of the interventricular septum occurred, in which case it decreased; and 4)
fibrillar collagens involved in remodeling included the formation of either
collagen strands and fibers in a greater number of previously
collagen-free intermuscular spaces in pressure-overload
hypertrophy, or a dense crisscrossing latticework of fibers that encircled muscle fibers after
isoproterenol. Thus, an increase in
fibrillar collagen in pressure-overload
hypertrophy is partially adaptive in that it enhances the tensile strength and three-dimensional delivery of force by the myocardium, but at the expense of reducing distensibility. The appearance of a dense
collagen meshwork within the subendocardium after
isoproterenol can be considered pathological in that it entraps muscle fibers causing active stiffness to fall while impairing distensibility. Finally,
fibrosis may paradoxically reduce passive stiffness if it leads to a thinning of the interventricular septum.