Open Access
Ridout, Samuel James
Graduate Program:
Doctor of Philosophy
Document Type:
Date of Defense:
June 14, 2011
Committee Members:
  • David Nathan Proctor, Dissertation Advisor
  • David Nathan Proctor, Committee Chair
  • James Anthony Pawelczyk, Committee Member
  • Mosuk Chow, Committee Member
  • Urs Andreas Leuenberger, Committee Member
  • cardiac output
  • aging
  • women
  • plasma volume expansion
  • exercise
The impact of aging on skeletal muscle and systemic capacities for blood flow are incompletely understood and could differ between the sexes. This dissertation consists of 3 cross-sectional studies designed to better understand age- and sex-associated differences in this balance. The first two studies characterize age and sex differences in maximal leg vascular conductance responses to local ischemia (study 1) and maximal isolated quadriceps exercise (study 2), as well as the maximal cardiac output response to whole body exercise (study 2). The third study examined age differences in systemic and leg exercise hemodynamics and cardiac function in response to acute plasma volume (PV) expansion. In study 1, peak calf vasodilator capacity evoked by 10 min of arterial occlusion was examined as a function of age (20 to 79 yrs) in healthy women (197). These women exhibited a 5-7% per decade decline in peak calf blood flow and vascular conductance with increasing age, nearly twice the rate of decline observed in a similarly aged male cohort tested in an identical manner (182). This study suggested that maximal vasodilator capacity in the legs is better preserved with age in men than women. This sex difference was not explained by differences in aerobic fitness (peak cycle oxygen uptake), which declined similarly in men and women (i.e., 7-8% per decade). Matching of a subgroup of young and older subjects for fitness abolished the decline in vasodilator capacity in men but not in women, suggesting a sex-specific and fitness-independent effect of aging on the leg vasculature of women. Study 2 examined maximal cardiac output (graded treadmill exercise to maximal exertion) and peak contraction-induced leg blood flow (single knee extensor exercise to maximal exertion) in younger (20-30 yrs) and older (60-75 yrs) men and women. These findings indicated that systemic oxygen delivery capacity (maximal cardiac output and VO2peak) was positively correlated with active muscle vasodilator capacity, as measured by peak blood flow and conducting capacity of the contracting knee extensor muscles, in men but not women . This relationship was most pronounced in older men, regardless of how peripheral vasodilatory capacity was expressed or normalized. The disparate balance between maximal cardiac output and peripheral vascular reserve suggest different cardiovascular limitations to aerobic capacity in men and women particularly with aging. Study 3 attempted to further assess age and sex differences in the balance between central and peripheral blood flow during exercise. Phase 1 experiments showed that PV expansion via 5% albumin acutely raised cardiac stroke volume and output at rest and during exercise in young women and men. The effects of PV expansion on leg exercise hemodynamics were difficult to detect in older subjects and could not be dissociated from concurrent effects of hemodilution. Phase 2 (follow-up) studies incorporated high resolution echocardiographic methods to assess the effects of PV expansion and posture during resting conditions on cardiac filling parameters, indexes of filling pressure, and cardiac stroke volume and output. Additionally, these same echocardiographic metrics, along with C2H2 measurement of cardiac output, were acquired during upright cycling exercise up to near maximal exertion (80% of VO2peak). At rest, in both the supine and seated postures young and older women had approximately the same ventricular filling pressure (indexed as the ratio of early filling velocity to mitral annular velocity, E/E’). At this consistent filling pressure the young women were able to augment early filling and increase end-diastolic volume (and therefore stroke volume) to a greater extent than older in both the supine and seated postures. Cardiac output was more labile in the young women, rising significantly in the supine compared to seated posture during normovolemia, a response only seen during hypervolemia in older women, when filling pressure was the highest. Additionally, mitral valve deceleration slope was steeper and mitral annular velocity higher in the young women during both normovolemia and hypervolemia. These results collectively suggest a more compliant ventricle in young women and a lack of sufficient reserve capacity in the older heart to normalize filling parameters or diastolic function to values observed in the young at rest. Throughout exercise in the plasma volume expanded state the young had a more significant absolute increase in cardiac output than the older, mediated by a greater increase in stroke volume. This did not translate into an increase in whole body oxygen consumption and therefore appears only to have corrected the hemodilution attendant to the PV expansion in both groups. Collectively these studies demonstrate an aging female cardiovascular system that has both peripheral structural limits to vasodilation and a reduced ability to augment cardiac output via the Frank-Starling mechanism which could limit older women’s ability to support the blood flow demands of working muscles compared with young women. Further, the balance between peripheral dilatory capacity and cardiac function is sex-specific in aged humans. Collectively these results suggest different mechanisms for optimizing the perfusion of active muscle in older men and women and that further investigations into the function of the aging cardiovascular system should analyze each sex individually as both peripheral arterial function, cardiac function and the interplay between these two demonstrates sex-specificity.