DECREASED CONTRACTILE RESPONSES TO ISOPROTERENOL IN ISOLATED CARDIAC MYOCYTES FROM AGING GUINEA-PIGS

We have characterized the age-related changes of contractility and bet a-adrenoceptor function in isolated cardiac myocytes from guinea-pigs. We used either adult animals from 2 to 14 weeks of age, where body we ight increases linearly with age, or senescent ones aged between 53-65 weeks. There was some indication of a decrease in contractility in ma ximum Ca2+ with age, with significant differences between a young (les s than or equal to 4 weeks, weight <400 g) and aged (greater than or e qual to 8 weeks, weight >600 g) group in contraction amplitude express ed as percentage shortening (but not when expressed as mu m change in length) or contraction and relaxation velocities. This decline was con tinued into senescence, and ANOVA showed a significant difference betw een the three groups for contraction amplitude (percentage shortening, 12.2+/-0.9%, young, n=31; 9.5+/-0.6%, n=28 aged; 6.7+/-0.8%, n=6, sen escent; P=0.005), and contraction or relaxation velocities (P<0.001). There was a more pronounced decline in maximum response to isoproteren ol with age, ANOVA for the maximum isoproterenol response for the thre e divisions showed significant differences for percentage shortening ( 11.8+/-0.7%, n=30, young; 7.9+/-0.5%, n-28, aged and 5.5+/-1.l%, n=6, senescent; P<0.001), velocities of contraction (P<0.001) and relaxatio n (P<0.001), and normalized velocities of contraction (P<0.001) and re laxation (P<0.01) at maximum isoproterenol, as well as in ISO EC(50) ( P<0.001) and isoproterenol/Ca2+ Ca2+ ratio (P<0.02). A general decreas e in contractility of the myocyte occurs as the animal ages, with maxi mum contraction amplitude being reduced and velocity of contraction an d relaxation slowed. The effect was more pronounced for beta-adrenocep tor stimulation than for high Ca2+, suggesting a specific lesion in th e adenylate cyclase related pathway. Much of the change occurred betwe en the young adult (less than or equal to 4 weeks) and the aged adult (greater than or equal to 8 weeks), although the trend was continued i n senescent animals (>52 weeks).