Gramm, Courtney

Background Neurophysiological coupling between ventilation and locomotor muscle group III/IV muscle afferent fibers during exercise is an important relationship that favorably influences ventilation in young healthy adults. In contrast, we have shown that group III/IV locomotor muscle afferents provoke aberrant ventilation in aging heart failure patients, which is suggested to be a primary effect of heart failure. However, there remains a limited understanding of the effect of aging in the absence of cardiovascular disease on the group III/IV muscle afferent pathway. Subsystolic circulatory occlusion to elicit venous distension has been suggested to stimulate locomotor muscle afferent neurologic feedback. The purpose of this study was to compare ventilatory responses in young vs aging healthy adults during submaximal constant‐load exercise with intermittent bilateral subsystolic occlusion of locomotor muscles. Methods Healthy adults completed 2 visits (10 young [YNG] vs 9 OLD; age 22±1 vs 66±3 yrs, BSA 1.8±0.1 vs 1.9±0.1 m 2 ; % predicted peak VO 2 99±7 vs 115±7 %; peak workload 188±16 vs 144±9 W, respectively; age and workload P <0.05). Visit 1: peak exercise ergometry test. Visit 2: constant‐load cycle ergometry at 30% peak workload (YNG=56±5 vs OLD=43±3 W, P <0.05) with the first 3 min without cuffing (0 mm Hg) and intermittent subsystolic bilateral thigh cuff inflations to 20, 40, 60, 80, or 100 mm Hg for 2 min (randomized), with 2 min deflation between occlusions thereafter. Minute ventilation (V E ), respiratory rate (RR), tidal volume (V T ), oxygen uptake (VO 2 ) indexed to weight, carbon dioxide output (VCO 2 ), respiratory exchange ratio (RER), V E /VCO 2 , and end tidal partial pressure CO 2 (P ET CO 2 ) were measured continuously via breath by breath system. Results At rest, V E , RR, V T , or RER did not differ in YNG vs OLD ( P >0.05); whereas VO 2 (6.3±0.3 vs 3.9±0.2 mL/kg/min) and VCO 2 (0.3±0.0 vs 0.2± 0.0 L/min) were higher in YNG vs OLD (respectively, P <0.05). During all exercise occlusions, V E was higher in YNG vs OLD, with the largest difference at 100 mm Hg (36.7±1.7 vs 30.2±1.6 L/min, respectively, P <0.05). However, the % change from rest to 0 mm Hg or each cuff occlusion resulted in no differences in YNG vs OLD for V E ( P >0.05). In contrast, in YNG vs OLD, the largest % change from 0 mm Hg to the cuff occlusion resulting in between group differences included V E (3.3±3.0 vs 17.3±3.6 at 80 mm Hg, P <0.05), VCO 2 (2.3±2.3 vs 20.8±3.4 at 100 mm Hg, P <0.05) and V E /VCO 2 (7.0±2.6 vs 0.5±1.8 at 100 mm Hg, P <0.05). In addition, there was a trend for significant differences between YNG and OLD for V T (−1.2±4.4 vs 5.9±4.1 % at 80 mm Hg, P =0.15), VO 2 (−2.1±1.5 vs 3.3±1.8 %, at 100 mm Hg, P =0.09) and P ET CO 2 (−6.4±1.9 vs −2.3±1.4 % at 100 mm Hg, P =0.11). Conclusions These data suggest that aging is associated with altered ventilatory responses to venous occlusion of locomotor muscles during constant load submaximal exercise. These changes may be a result of an increased contribution of locomotor muscle afferents on ventilatory control with aging. Support or Funding Information none

Introduction Healthy aging in adults is associated with attenuated cardiac output (Q) for a given exercise workload compared to younger healthy adults. This is important because skeletal muscle perfusion pressure during exercise is dependent on coordinated adjustments between cardiac and vascular hemodynamics. Cardiac power (CP) quantifies the flow and peripheral pressure generating capacity of the heart, and may be the strongest measure of cardiac function during exercise. Group III/IV muscle afferents are suggested to favorably influence Q and arterial pressure during exercise in young healthy adults. However, the influence of group III/IV afferents on cardiac hemodynamic and arterial pressure coupling during exercise remains unclear across the aging spectrum. Venous distension via subsystolic circulatory occlusion of locomotor muscles is suggested to increase group III/IV afferent outflow. The aim of this study was to assess the influence of subsystolic circulatory occlusion of locomotor muscles on CP in young vs aging healthy adults. Methods Healthy adults completed 2 visits (10 young [YNG] vs 9 OLD; age 22±1 vs 66±3 yrs, BSA 1.8±0.1 vs 1.9±0.1 m 2 ; % predicted peak VO 2 99±7 vs 115±7 %; peak workload 188±16 vs 144±9 W, respectively; age and workload P <0.05). Visit 1: peak exercise test. Visit 2: constant load cycle ergometry at 30% peak workload (YNG=56±5 vs OLD=43±3 W, P <0.05) with the first 3 min without cuffing (0 mm Hg), but thereafter included intermittent subsystolic bilateral thigh cuff inflations to 20, 40, 60, 80, or 100 mm Hg for 2 min (randomized), with 2 min deflation between inflations. Non‐invasive Q and mean arterial (MAP) pressure were measured using continuous hemodynamic photoplethysmography. We calculated CP=Q*MAP. Q and CP were indexed to BSA. Results At rest, MAP did not differ in YNG vs OLD, but Q and CP were higher in YNG vs OLD (P<0.05), which persisted throughout each exercise cuff occlusion. In YNG, the greatest increase in CP from 0 mm Hg occurred at 100 mm Hg (754±48 vs 899±48 L/min/m 2 · mm Hg, P <0.05) due to increased MAP (19±4%, P <0.05) but not Q (1±2%, P >0.05). In OLD, Q, MAP, and CP did not differ between 0 mm Hg and any occlusion ( P >0.05). The % increase in Q from rest to 0, 20, 60, 80, and 100 mm Hg was higher in YNG vs OLD ( P <0.05). The % increase in MAP from rest to any occlusion did not differ in YNG vs OLD ( P >0.05). The % increase in CP from rest to occlusions of 60 (130±9 vs 98±11%), 80 (142±9 vs 108±20%), and 100 (158±11 vs 114±14%) were higher in YNG vs OLD (all P <0.05). Within YNG, the % increase in CP from rest to 100 mm Hg was higher than the % increase from rest to 0, 20, 40, or 60 mm Hg ( P <0.05), driven by increased MAP ( P <0.05). Within OLD, these differences for % increase in CP did not occur despite MAP that was similar to YNG ( P >0.05). Conclusions These data suggest that CP is attenuated in OLD vs YNG healthy adults during subsystolic circulatory occlusion of locomotor muscles during submaximal constant load exercise. The reduced CP generation in older adults is related to a blunted increase in Q mediated by attenuated influence of group III/IV muscle afferents on cardiac function during exercise.

Although pathophysiological links between postmenopause and healthy aging remain unclear, both factors are associated with increased blood pressure and sympathetic nerve activity (SNA) in women. Activation of polymodal musculoskeletal neural afferents originating within adventia of venules modulates SNA and blood pressure control during exercise in healthy adults. We hypothesized transient subsystolic regional circulatory occlusion (RCO) during exercise sensitizes these afferents leading to augmented systemic vascular resistance (SVR)-mediated increased mean arterial pressure (MAP) in postmenopause vs. premenopause. Normotensive women in premenopause or postmenopause ( n = 14 and 14; ages: 30 ± 9 and 55 ± 7 yr, respectively; P < 0.01) performed: 1) peak exercise testing and 2) fixed-load cycling at 30% peak workload (48 ± 11 and 38 ± 6 W, respectively; P < 0.01), whereby the initial 3 min were control exercise without RCO (CTL), thereafter including 2 min of bilateral-thigh RCO to 20, 40, 60, 80, or 100 mmHg (randomized), with 2 min deflation between RCO. Both MAP (17 ± 4 vs. 4 ± 4%, P = 0.02) and SVR (16 ± 8 vs. −3 ± 8%, P = 0.04) increased at 80 mmHg from CTL in postmenopause vs. premenopause, respectively. However, cardiac index was similar in postmenopause vs. premenopause at 80 mmHg from CTL (1 ± 6 vs. 7 ± 6%, respectively; P = 0.15). There was no continuous effect of aging in MAP ( P = 0.12), SVR ( P = 0.07), or cardiac index ( P = 0.18) models. These data suggest transient locomotor subsystolic RCO sensitizes musculoskeletal afferents, which provoke increased SVR to generate augmented MAP during exercise in postmenopause. These observations provide a novel approach for understanding the age-independent variability in exercise blood pressure control across the normotensive adult pre- to postmenopause spectrum.