Alterations in mechanical response of aged rat myocardium. Effects of dexamethasone

1. Mechanical responses of young and old rat myocardium to increasing rates of stimulation were compared. As the animals aged, we found a significant enhancement of the negative force-frequency response and a decline in the velocities of contraction and of relaxation. 2. At 6 months of age, there were no differences between rats obtained from commercial sources and a group of rats obtained from a colony maintained at the National Institute of Aging. 3. At 24 months, the negative force-frequency response was considerably greater in the former group of animals than in the latter. 4. The sensitivity to the calcium concentration in the tissue bathing solution was significantly increased in aged heart preparations. Increasing the calcium concentration reduced the negative inotropy and the decline in the velocities of contraction and relaxation. The enhancement by calcium was directly proportional to the concentration of the metal in the bathing solution. 5. When aged animals were pretreated with pharmacological doses of dexamethasone, the age-induced alterations in the mechanical responses were reversed. The aged, dexamethasone-treated myocardium also became refractory to calcium concentrations above 2.7 mM in the bathing solution. 6. It is suggested that aging induces multifocal defects and that steroid hormones play a role in the maintenance of integrity of the myocardium. The action of the steroids is on the sarcolemma, the contractile proteins and the sarcoplasmic reticulum.