Abstract 1599: Decreased Intrinsic Heart Rate and β-adrenergic Responsiveness Contribute to the Decline in Maximal Heart Rate with Human Aging
Background- Maximal aerobic exercise capacity decreases with aging and is closely linked with reductions in functional capacity, independence and quality of life in older adults. A reduction in maximal heart rate (HR) is the most consistent and physiologically important contributor to reductions in maximal exercise capacity with aging. Despite its importance, however, the mechanism(s) involved in age-associated reductions in maximal HR are unknown.
Methods and Results- To test the hypothesis that intrinsic HR (HR during acute ganglionic blockade [GB] with intravenous trimethaphan) and chronotropic β-adrenergic receptor responsiveness (β-ARR, increase in HR with incremental intravenous infusion of isoproterenol during GB; slope of change in HR/[isoproterenol]) partially explain age-related differences in maximal HR (Balke treadmill exercise protocol to exhaustion) 15 older (65±1 yr) and 15 young (25±1 yr) healthy men were studied. Maximal HR was lower in the older compared with the young men (162±2 vs. 191±3 beats/min, P<0.0001). In the entire group, maximal HR was positively related to intrinsic HR (r=0.87, P<0.0001) and chronotropic β-ARR (r=0.61, P<0.0001). After partialling out the effects of intrinsic HR and chronotropic β-ARR, the age-related difference in maximal HR (29 beats/min) was reduced by 83% (to 5 beats/min) and was no longer significant (P<0.2). Intrinsic HR explained uniquely 37% of the variance in maximal HR (P<0.0005), independent of age and chronotropic β-ARR. Chronotropic β-ARR explained uniquely 14% of the variance in maximal HR (P<0.03), independent of age and intrinsic HR. Accounting for the influence of intrinsic HR, chronotropic β-ARR and age collectively accounted for 79% of the variance in maximal HR in the entire group (P<0.0001).
Conclusions- Together, reduced intrinsic HR and chronotropic β-ARR explain most of the age-related decline in maximal HR in healthy humans, with decreased intrinsic HR playing the greater role. Our findings provide the first direct experimental evidence that intrinsic HR and chronotropic β-ARR are key determinants of maximal HR in healthy humans and may play a major role in mediating the age-associated reductions in maximal aerobic capacity.