Proctor, David N.

Purpose: Supervised walking exercise is a critical component of rehabilitation for patients with peripheral artery disease (PAD); however, various barriers could limit participation in such programs, highlighting the need for accessible exercise strategies that may facilitate a gradual transition to more intensive physical activity while improving vascular function and walking performance in this population. We examined the hypothesis that static muscular stretching would improve microvascular function and walking ability in patients with PAD. Methods: Thirty-six PAD patients, classified as Fontaine Stage II or III, were randomized into stretching or non-stretching groups. The stretching group performed daily calf stretching using an ankle dorsiflexion splint for 30 minutes, 5 days a week, for 4 weeks. The six-minute walk test (6MWT) and a vascular occlusion test were used to assess changes in walking ability and calf microvascular function before and after the intervention. Results: Microvascular hyperemic reperfusion significantly increased in the treatment group (4958±1111 to 5749±1459 %*s, p=0.034), with no change observed in the control group (5502±1231 to 5022±1160 %*s, p=0.155). 6MWT total walking distance increased in all participants (260±88 to 285±85 m, p=0.004). A moderate but non-significant correlation was observed between the changes in 6MWT and total walking distance and reperfusion index in the treatment group (r=0.45, p=0.26). Conclusions: Static muscular stretching improves microvascular perfusion in the calf muscles, which may contribute to improvement in walking ability in patients with PAD. This low-cost and time-saving intervention may serve as a gradual transition to traditional supervised walking exercise rehabilitation, especially in patients with severely impaired walking ability.

Introduction: Peripheral artery disease (PAD), an atherosclerotic disease of the peripheral arteries, also results in microvascular dysfunction. PAD patients are recommended to undergo supervised walking and medical management; however, compliance with supervised walking programs is limited due to inconvenience and pain, necessitating alternative non-pharmacological interventions. We have shown that daily muscle stretching improved microvascular function in aged rats. This prompted us to study the effect of daily muscle stretching on microvascular function of the calf muscles in PAD patients. Methods: A randomized, single-blinded study was conducted on 24 PAD patients. Patients were assigned to either stretching or placebo stretching using a dorsiflexion splint (Image 1) for 30 min/day, 5 days/wk for 4 wks. Calf muscle oxygen saturation (smO 2 ) was recorded using near-infrared spectroscopy during the six-minute walking test (6MWT) before (Visit 1) and after (Visit 2) stretching or placebo stretching. The percentage decrease in smO 2 (from baseline) at minute 1 (Δ1) and minute 2 (Δ2) of the 6MWT was determined. Two-way ANOVA was used to compare Δ1 and Δ2 between the stretching and placebo stretching groups. Results: The mean age of the patients was 74.1±11.4 yrs with 52% (13/23) males. There was no significant difference in the changes in smO 2 during the 6MWT at either minute 1 (Δ1: 44.1±7.3% vs 27.1±7.0%, p=0.12) or minute 2 (Δ2: 78.7±8.2% vs 58.1±7.9%, p=0.08) between the stretching group and placebo stretching group at Visit 1. In contrast, at Visit 2, there was a significantly greater change in smO 2 at minute 2 (D2: 83.1±8.2% vs 51.3±7.9%, p=0.008) in the stretching group compared to the placebo stretching group with a trend towards a statistically greater change in smO 2 at minute 1 (Δ1: 39.0±7.3% vs 20.4±7.0%, p=0.06) (Image 2). Conclusion: Daily stretching of the calf muscles for 4 weeks is associated with increased oxygen extraction by the calf muscles during walking.

Whole body and mixed muscle protein synthesis rate declines with age in healthy people. In response to a 4‐month aerobic exercise program we showed that mixed muscle protein synthesis rate increased 22%. Several gene transcripts that encode mitochondrial (mito) proteins increased in response to exercise but it remains to be determined whether these are translated to protein synthesis. In this study we tested the hypothesis that mito protein synthesis also increased in response to aerobic exercise training. Healthy men and women (N = 42) from 30–74 y were studied before and after a 4‐month program of stationary bicycle training (3d/wk, up to 40min/d at 80% HRmax) or control activity. Muscle protein synthesis rate was measured using [ 15 N] phenylalanine as a tracer. Mito and sarcoplasmic (sarco) proteins were separated from muscle biopsies for analysis. At baseline there was a decline with age (p<0.05) in both mito (6%/decade, r= −0.32) and sarco (5.5%/decade, r= −0.42) protein synthesis rate. Muscle protein synthesis rates did not change in control subjects, but in the exercise group mito synthesis increased 27% (0.046 ± 0.003 %/h pre vs. 0.058 ± 0.005 post, p=0.017, N=25) and there was a trend for 10% higher sarco protein synthesis (0.036 ± 0.002 %/h pre vs. 0.040 ± 0.003 post, p=0.066, N=33). These effects of exercise did not vary with age. We conclude that despite a decline in mito protein synthesis and function with advancing age, the potential for mito biogenesis in response to aerobic exercise remains robust in older muscle, as demonstrated by enhanced mito protein synthesis, gene expression, and enzyme action. Support: NIH RO1DK41973, MO1RR00585.

Maximum velocity of the actomyosin ATPase reaction ( VmaxATPase) and ATP consumption rate during maximum isometric activation (ATPiso) were determined in human vastus lateralis (VL) muscle fibers expressing different myosin heavy chain (MHC) isoforms. We hypothesized that the reserve capacity for ATP consumption [1 − (ratio of ATPisoto VmaxATPase)] varies across VL muscle fibers expressing different MHC isoforms. Biopsies were obtained from 12 subjects (10 men and 2 women; age 21–66 yr). A quantitative histochemical procedure was used to measure VmaxATPase. In permeabilized fibers, ATPisowas measured using an NADH-linked fluorometric procedure. The reserve capacity for ATP consumption was lower for fibers coexpressing MHC2Xand MHC2Acompared with fibers singularly expressing MHC2Aand MHCslow(39 vs. 52 and 56%, respectively). Tension cost (ratio of ATPisoto generated force) also varied with fiber type, being highest in fibers coexpressing MHC2Xand MHC2A. We conclude that fiber-type differences in the reserve capacity for ATP consumption and tension cost reflect functional differences such as susceptibility to fatigue.

An open-circuit (OpCirc) acetylene uptake cardiac output (Q˙t) method was modified for use during exercise. Two computational techniques were used. OpCirc1 was based on the integrated uptake vs. end-tidal change in acetylene, and OpCirc2 was based on an iterative finite difference modeling method. Six subjects [28–44 yr, peak oxygen consumption (V˙o2) = 120% predicted] performed cycle ergometry exercise to compareQ˙t using OpCirc and direct Fick methods. An incremental protocol was repeated twice, separated by a 10-min rest, and subsequently subjects exercised at 85–90% of their peak work rate. Coefficient of variation of the OpCirc methods and Fick were highest at rest (OpCirc1, 7%, OpCirc2, 12%, Fick, 10%) but were lower at moderate to high exercise intensities (OpCirc1, 3%, OpCirc2, 3%, Fick, 5%). OpCirc1 and OpCirc2 Q˙t correlated highly with Fick Q˙t( R2= 0.90 and 0.89, respectively). There were minimal differences between OpCirc1 and OpCirc2 compared with Fick up to moderate-intensity exercise (<70% peakV˙o2); however, both techniques tended to underestimate Fick at >70% peakV˙o2. These differences became significant for OpCirc1 only. Part of the differences between Fick and OpCirc methods at the higher exercise intensities are likely related to inhomogeneities in ventilation and perfusion matching ( R2= 0.36 for Fick − OpCirc1 vs. alveolar-to-arterial oxygen tension difference). In conclusion, both OpCirc methods provided reproducible, reliable measurements ofQ˙t during mild to moderate exercise. However, only OpCirc2 appeared to approximate FickQ˙t at the higher work intensities.

It is currently unclear whether aging alters the perfusion of active muscles during large-muscle dynamic exercise in humans. To study this issue, direct measurements of leg blood flow (femoral vein thermodilution) and systemic arterial pressure during submaximal cycle ergometry (70, 140, and 210 W) were compared between six younger (Y; 22–30 yr) and six older (O; 55–68 yr) chronically endurance-trained men. Whole body O2uptake, ventilation, and arterial and femoral venous samples for blood-gas, catecholamine, and lactate determinations were also obtained. Training duration (min/day), estimated leg muscle mass (dual-energy X-ray absorptiometry; Y, 21.5 ± 1.2 vs. O, 19.9 ± 0.9 kg), and blood hemoglobin concentration (Y, 14.9 ± 0.4 vs. O, 14.7 ± 0.2 g/dl) did not significantly differ ( P > 0.05) between groups. Leg blood flow, leg vascular conductance, and femoral venous O2 saturation were ∼20–30% lower in the older men at each work rate (all P < 0.05), despite similar levels of whole body O2 uptake. At 210 W, leg norepinephrine spillover rates and femoral venous lactate concentrations were more than twofold higher in the older men. Pulmonary ventilation was also higher in the older men at 140 (+24%) and 210 (+39%) W. These results indicate that leg blood flow and vascular conductance during cycle ergometer exercise are significantly lower in older endurance-trained men in comparison to their younger counterparts. The mechanisms responsible for this phenomenon and the extent to which they operate in other groups of older subjects deserve further attention.

Proctor, David N., Kenneth C. Beck, Peter H. Shen, Tamara J. Eickhoff, John R. Halliwill, and Michael J. Joyner. Influence of age and gender on cardiac output-V˙o2relationships during submaximal cycle ergometry. J. Appl. Physiol. 84(2): 599–605, 1998.—It is presently unclear how gender, aging, and physical activity status interact to determine the magnitude of the rise in cardiac output (Q˙c) during dynamic exercise. To clarify this issue, the present study examined theQ˙c-O2uptake (V˙o2) relationship during graded leg cycle ergometry in 30 chronically endurance-trained subjects from four groups ( n = 6–8/group): younger men (20–30 yr), older men (56–72 yr), younger women (24–31 yr), and older women (51–72 yr). Q˙c (acetylene rebreathing), stroke volume (Q˙c/heart rate), and whole bodyV˙o2were measured at rest and during submaximal exercise intensities (40, 70, and ∼90% of peakV˙o2). Baseline resting levels of Q˙c were 0.6–1.2 l/min less in the older groups. However, the slopes of theQ˙c-V˙o2relationship across submaximal levels of cycling were similar among all four groups (5.4–5.9 l/l). The absolute Q˙c associated with a given V˙o2(1.0–2.0 l/min) was also similar among groups. Resting and exercise stroke volumes (ml/beat) were lower in women than in men but did not differ among age groups. However, older men and women showed a reduced ability, relative to their younger counterparts, to maintain stroke volume at exercise intensities above 70% of peakV˙o2. This latter effect was most prominent in the oldest women. These findings suggest that neither age nor gender has a significant impact on theQ˙c-V˙o2relationships during submaximal cycle ergometry among chronically endurance-trained individuals.

This study evaluated the hypothesis that active muscle blood flow is lower during exercise at a given submaximal power output after aerobic conditioning as a result of unchanged cardiac output and blunted splanchnic vasoconstriction. Eight untrained subjects (4 men, 4 women, 23–31 yr) performed high-intensity aerobic training for 9–12 wk. Leg blood flow (femoral vein thermodilution), splanchnic blood flow (indocyanine green clearance), cardiac output (acetylene rebreathing), whole body O2 uptake (V˙o 2), and arterial-venous blood gases were measured before and after training at identical submaximal power outputs (70 and 140 W; upright 2-leg cycling). Training increased ( P < 0.05) peak V˙o 2(12–36%) but did not significantly change submaximalV˙o 2 or cardiac output. Leg blood flow during both submaximal power outputs averaged 18% lower after training ( P = 0.001; n = 7), but these reductions were not correlated with changes in splanchnic vasoconstriction. Submaximal leg V˙o 2 was also lower after training. These findings support the hypothesis that aerobic training reduces active muscle blood flow at a given submaximal power output. However, changes in leg and splanchnic blood flow resulting from high-intensity training may not be causally linked.

Proctor, David N., and Kenneth C. Beck. Delay time adjustments to minimize errors in breath-by-breath measurement ofV˙o2during exercise. J. Appl. Physiol. 81(6): 2495–2499, 1996.—If the delay time between gas concentration and flow signals is not adequately corrected during breath-by-breath analysis of expired gas, an error in calculation of oxygen consumption (V˙o2) will result. To examine the frequency and delay time dependences of errors inV˙o2measurement, six healthy men exercised at 100, 200, and 250 W on a cycle ergometer while breath-by-breath assessment ofV˙o2was made simultaneously with collection of expired air. Subjects breathed first at normal rates (15–30 breaths/min) and then at 70 breaths/min. Each subject performed each level of exercise twice by using erroneous values for the delay time between gas concentration and flow signals. At normal breathing frequencies, errors inV˙o2measurement were ±10% over the full range of delay times used, and the errors were not tightly correlated with variations in delay times from optimum. However, at 70 breaths/min, errors approached ±30% as the variations in delay times deviated ±0.1 s from the optimal, and the errors were highly correlated with the variations in delay times. We conclude that there is greater potential for errors inV˙o2measurement with incorrect delay time at higher breathing frequencies. These findings suggest that the optimal delay time for breath-by-breath systems should be adjusted by using high breathing frequencies.

We previously reported that epinephrine stimulates leg free fatty acid (FFA) release in men but not in women. The present studies were conducted to determine whether the same is true during exercise. Six men and six women bicycled for 90 min at 45% of peak O2 consumption, during which time systemic and leg FFA kinetics ([9,10-3H]palmitate) were measured. The catecholamine and hormonal responses to exercise were not different in men and women. The baseline systemic and leg palmitate release was 94 ± 15 vs. 114 ± 5 μmol/min and 16 ± 2 and 20 ± 3 μmol/min, respectively, in men and women [ P = nonsignificant (NS)]. Systemic and leg palmitate release increased (both P < 0.001) to 251 ± 18 vs. 212 ± 16 μmol/min and 73 ± 19 vs. 80 ± 12 μmol/min in men and women, respectively, during the last 30 min of exercise ( P = NS, men vs. women). We conclude that the systemic and leg adipose tissue lipolytic response to exercise is not different in nonobese men and women.