Studies on the mechanism of the age-related change in swelling ability of human myocardium.

Previous studies have shown that human myocardium loses its ability to swell at pH 11.2 with increasing age. This investigation indicated that the age-related difference does not exist at the subccllular level or after treatment with collagenase. Swelling did not correlate well with myofiber size or acid and base binding capacity. It was concluded that the increased rigidity with age is due to the development of a more rigid intercellular collagenous connective tissue. A PREVIOUS study was carried out to discover if cardiac failure and decreased cardiac output in aged individuals, in the absence of significant coronary artery disease, might be due to or correlated with, an underlying age-related molecular change in myocardium. 1 That investigation indicated that human myocardium undergoes a diminution in ability to swell at pll 11.2 after approximately 30 years of age. In accordance with the Donnan equilibrium theory of protein swelling, 2 this finding was interpreted to mean that myocardium became more rigid with advancing age. It was suggested that an increased rigidity with age might be due to an increased number of cross linkages between myocardial protein molecules. There are, however, other possible mechanisms for the loss of swelling ability with age. Connective tissue around the myocardial fibers might restrict swelling. In the previous study it was shown that the collagen concentration in the heart specimens did not increase with age. However, collagen itself has been shown to become more rigid with advancing age,* and restriction of myocar-dial swelling might be due to a change in the physical state, rather than amount of collagen. Another possibility is that swelling ability is related to myofiber size, and the latter changes as a function of age. A third possible mechanism is as myocardium ages, it undergoes a change in osmotic properties. Loss of swelling ability at a specific pH without an increase in restricting factors requires a variation in total number of acidic or basic groups of the insoluble fibrous protein which swells. This view is based on the studies of protein swelling by Proctor and Wilson. 2 The present investigation was undertaken in an attempt to obtain data which would indicate if any of the suggested mechanisms might be responsible for the age-related change in myocardial swelling ability. If the change is in the myocardial proteins per se, and not in surrounding tissue, subcellular myofibril bundles and isolated myofibrils should show a loss of swelling …