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Cardiac dilatation associated with collagen alterations
J B Caulfield1, P Norton, R D Weaver
1University of Alabama, Department of Pathology, Birmingham 35294-0019.
Insights
Disrupting the heart's collagen network with disulfide reagents did not affect contractility but caused significant ventricular dilation. The collagen weave complex is crucial for maintaining the heart's structural integrity and pressure-volume relationship.
Area of Science:
- Cardiovascular Biology
- Biochemistry
- Structural Biology
Background:
- The heart possesses a complex collagen network crucial for its mechanical function.
- Previous studies have assigned functions to collagen components based on structure and location.
- Demonstrating specific functional roles within this hierarchical network remains challenging.
Purpose of the Study:
- To investigate the functional role of specific collagen components in the heart.
- To determine the impact of disrupting the cardiac collagen network on ventricular mechanics.
- To elucidate the contribution of the collagen weave complex to pressure-volume dynamics.
Main Methods:
- Intravenous infusions of disulfide reagents to activate a collagenolytic system.
- Assessment of cardiac collagen structure, myocyte contractility, and force generation.
- Evaluation of ventricular pressure-volume relationships and distensibility.
Main Results:
- Disulfide treatment led to near-complete loss of collagen struts interconnecting myocytes and capillaries, and the myocyte-surrounding weave complex.
- No significant changes were observed in myocyte contractility or force delivery under increased preload or afterload.
- Disulfide-treated hearts exhibited marked ventricular dilatation and increased distensibility, with a rightward shift in pressure-volume curves.
Conclusions:
- The cardiac collagen network, particularly the weave complex, plays a critical role in maintaining ventricular stiffness and shape.
- Disruption of this network impairs passive diastolic properties without affecting active contractile function.
- The weave complex significantly contributes to the initial rectilinear phase of the pressure-volume curve, indicating its importance in diastolic function.
Abstract:
There is a complex collagen network in the heart. Various components have been identified and generally on the basis of form and position some functions have been ascribed to one or another of these components. Since the various components all appear to be connected in a hierarchial network of some type assigning function is not difficult but demonstrating a given function is somewhat hazardous. We have demonstrated that two I.V. infusions of disulfide reagents one week apart activates a collagenolytic system that results in near complete loss of the collagen struts that interconnect myocytes, the collagen struts that connect capillaries to all adjacent myocytes and the weave complex that surrounds groups of myocytes. Increases in pre load or afterload result in responses indicating that the disulfide treated animals generate pressure equal to or greater than the control hearts, thus, the treatment has no affect on either myocyte contractility or force delivery to the ventricle. However, static pressure volume measurements in the disulfide treated animals are shifted far to the right indicating marked dilatation of the ventricle and increase in distensibility. This indicates that the weave complex contributes to the initial rectilinear portion of the pressure volume curve.