The effect of advanced age on the response of active tension, maximal rate of tension development (dT/dt), and contraction duration to catecholamines and to calcium was evaluated in isometric trabeculae carneae from young adult (6-month-old), middle-aged (12-month-old), and aged (25-month-old) rats. Control values were not age dependent except for that for contraction duration which was prolonged in the aged group. At a norepinephrine concentration of 8 times 10-5M, dT/dt increased to 163.8 plus or minus 5.3% of control in the young adult group and to 125.9 plus or minus 6.3% of control in the aged group (P smaller than 0.001). Active tension increased to 121.3 plus or minus 4.0% of control in the young adult muscles but did not increase in the aged muscles (P smaller than 0.01). Contraction duration shortened proportionately in both age groups. Similar results were obtained with isoproterenol. In contrast to the response to catecholamines, there was no age difference in the response of active tension and dT/dt to increasing concentrations of calcium. It is concluded that the intrinsic inotropic response to catecholamines is diminished in the aged myocardium. This finding does not appear to result from differences in tachyphylaxis, tissue uptake of catecholamines, or the ability of the contractile proteins to respond to increasing concentrations of calcium but instead may result from a decreased ability of catecholamines to increase the intracellular calcium available for contraction.
A B S T R A C T Isometric performance at 29'C was measured in left ventricular trabeculae carneae from young adult (6-mo) and aged (25-mo) rats (n = 18 in each group). Active tension and maximal rate of tension development did not differ with age, but contraction duration was 255±6 ms in the young adult and 283±6 ms in the aged group (P < 0.001). Although catecholamine content per gram heart weight was less in the aged myocardium, additional experiments showed that neither 1 X 10' M propranolol nor pretreatment with 6-hydroxydopamine eliminated the age difference in contraction duration. To determine if this age difference resulted from a prolonged active state, electromechanical dissociation and the overshoot of contraction duration during recovery from hypoxia were measured. During paired stimulation greater mechanical refractoriness was found in aged muscles (P < 0.01), but intracellular action potential recordings showed no age difference in the electrical refractory period. On recovery from hypoxia, contraction duration overshoot was 117±4% of control in the young and 138±4% of control in the aged muscles (P < 0.01). The greater electromechanical dissociation and greater overshoot in contraction duration following hypoxia in aged myocardium suggests that prolonged contraction duration in aged myocardium results from a prolonged active state rather than changes in passive properties or myocardial catecholamine content.
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