Michael A. Welsch

Neuroendocrine Activation in Heart Failure Is Modified by Endurance Exercise Training

Abstract OBJECTIVES The purpose of this study was to determine whether endurance exercise training could buffer neuroendocrine activity in chronic heart failure patients. BACKGROUND Neuroendocrine activation is associated with poor long-term prognosis in heart failure. There is growing consensus that exercise may be beneficial by altering the clinical course of heart failure, but the mechanisms responsible for exercise-induced benefits are unclear. METHODS Nineteen heart failure patients (ischemic disease; New York Heart Association [NYHA] class II or III) were randomly assigned to either a training group or to a control group. Exercise training consisted of supervised walking three times a week for 16 weeks at 40% to 70% of peak oxygen uptake. Medications were unchanged. Neurohormones were measured at study entry and after 16 weeks. RESULTS The training group (n = 10; age = 61 ± 6 years; EF = 30 ± 6%) and control group (n = 9; age = 62 ± 7 years; EF = 29 ± 7%) did not differ in clinical findings at study entry. Resting levels of angiotensin II, aldosterone, vasopressin and atrial natriuretic peptide in the training and control groups did not differ at study entry (5.6 ± 1.3 pg/ml; 158 ± 38 pg/ml; 6.1 ± 2.0 pg/ml; 37 ± 8 pg/ml training group vs. 4.8 ± 1.2; 146 ± 23; 4.9 ± 1.1; 35 ± 10 control group). Peak exercise levels of angiotensin II, aldosterone, vasopressin and atrial natriuretic peptide in the exercise and control groups did not differ at study entry. After 16 weeks, rest and peak exercise hormone levels were unchanged in control patients. Peak exercise neurohormone levels were unchanged in the training group, but resting levels were significantly (p CONCLUSIONS Our data indicate that 16 weeks of endurance exercise training modified resting neuroendocrine hyperactivity in heart failure patients. Reduction in circulating neurohormones may have a beneficial impact on long-term prognosis.

Concurrent cardiovascular and resistance training in healthy older adults.

PURPOSE The recommendations for exercise training and physical activity for older adults include cardiovascular and resistance training components (CVT and RT, respectively). The purpose of the present investigation was to compare the fitness benefits of concurrent CVT and RT with those attained through an equivalent duration of CVT or RT alone. METHODS Thirty-six participants (ages 60-84) were assigned to a control group or to one of three exercise treatment groups. The treatment groups exercised three times per week for 12 wk using RT (N = 11), CVT (N = 10), or CVT and RT (BOTH, N = 9). Pre- and post-training, participants performed a submaximal exercise test (GXT), five repetition-maximum strength tests (5RM), and the AAHPERD functional fitness test for older adults. RESULTS All exercise treatment groups revealed lower resting heart rate and rate-pressure product; lower exercise diastolic blood pressure and rating of perceived exertion; increased GXT duration; increased leg, back, and shoulder 5RM scores; and improved AAHPERD flexibility, coordination, and cardiovascular endurance scores. The exercise treatment groups responded differently on the following: RT and BOTH enhanced arm and chest strength more than CVT; and BOTH enhanced AAHPERD strength and agility scores more than CVT or RT. CONCLUSIONS Concurrent CVT and RT is as effective in eliciting improvements in cardiovascular fitness and 5RM performance as CVT or RT, respectively. Moreover, incorporating both CVT and RT in exercise programs for older adults may be more effective in optimizing aspects of functional fitness than programs that involve only one component.

Effect of resistance training volume on strength and muscle thickness

The purpose of this study was to determine the effects of different volumes of high-intensity resistance training on isometric torque and muscle thickness. Training was conducted three times per week using one set (low volume, EX-1, N = 18) or three sets (high volume, EX-3, N = 20) of dynamic variable resistance exercise. Ten subjects acted as nontraining controls (CONT). Bilateral knee extension (KEXT) and flexion (KFLEX) exercise was performed to fatigue within 8-12 repetitions for 14 wk. Maximal isometric KEXT and KFLEX torque was tested at 6 degrees, 24 degrees, 42 degrees, 60 degrees, 78 degrees, 96 degrees, and 108 degrees of KFLEX using a MedX (Ocala, FL) KEXT/KFLEX ergometer. The anterior (ANT), lateral (LAT), and posterior (POST) right thigh, the medialis muscle (MED), and the lateralis muscle (LATER) were assessed for thickness by B-mode ultrasound (ULTRA). Both training groups improved torque output at most angles, but there was no difference between EX-1 and EX-3 (P > or = 0.05). ULTRA detected increases in muscle thickness for EX-1 at 60% LAT and 40% and 60% POST. EX-3 increased muscle thickness at the MED, and 40% and 60% POST. In conclusion, one set of high intensity resistance training was as effective as three sets for increasing KEXT and KFLEX isometric torque and muscle thickness in previously untrained adults.

Resistance exercise training restores bone mineral density in heart transplant recipients

OBJECTIVES This was a prospective, randomized, controlled study designed to determine the effect of resistance exercise training on bone metabolism in heart transplant recipients. BACKGROUND Osteoporosis frequently complicates heart transplantation. No preventative strategy is generally accepted for glucocorticoid-induced bone loss. METHODS Sixteen male heart transplant recipients were randomly assigned to a resistance exercise group that trained for 6 months (mean [+/- SD] age 56 +/- 6 years) or a control group (mean age 52 +/- 10 years) that did not perform resistance exercise. Bone mineral density (BMD) of the total body, femur neck and lumbar spine (L2 to L3) was measured by dual-energy X-ray absorptiometry before and 2 months after transplantation and after 3 and 6 months of resistance exercise or a control period. The exercise regimen consisted of lumbar extension exercise (MedX) performed 1 day/week and variable resistance exercises (Nautilus) performed 2 days/week. Each exercise consisted of one set of 10 to 15 repetitions performed to volitional fatigue. RESULTS Pretransplantation baseline values for regional BMD did not differ in the control and training groups. Bone mineral density of the total body, femur neck and lumbar vertebra (L2 to L3) were significantly decreased below baseline at 2 months after transplantation in both the control (-3.3 +/- 1.3%, -4.5 +/- 2.8%, -12.7 +/- 3.2%, -14.8 +/- 3.1%, respectively). Six months of resistance exercise restored BMD of the whole body, femur neck and lumbar vertebra to within 1%, 1.9% and 3.6% of pretransplantation levels, respectively. Bone mineral density of the control group remained unchanged from the 2-month posttransplantation levels. CONCLUSIONS Within 2 months after heart transplantation, approximately 3% of whole-body BMD is lost, mostly due to decreases in trabecular bone (-12% to -15% of lumbar vertebra). Six months of resistance exercise, consisting of low back exercise that isolates the lumbar spine and a regimen of variable resistance exercises, restores BMD toward pretransplantation levels. Our results suggest that resistance exercise is osteogenic and should be initiated early after heart transplantation.

Resistance exercise prevents glucocorticoid-induced myopathy in heart transplant recipients.

PURPOSE To determine the effect of resistance exercise training (ET) on glucocorticoid-induced myopathy in heart transplant recipients (HTR), 14 male HTR were randomly assigned to a ET group that trained for 6 months (54 +/- 3 yr old; mean +/- SD) or a control group (51 +/- 8 yr old; mean +/- SD). METHODS Fat mass, fat-free mass, and total body mass were measured by dual-energy x-ray absorptiometry before and 2 months after transplantation (Tx), and after 3 and 6 months of ET or control period. The exercise regimen consisted of lumbar extension (MedX) performed 1 d.wk-1 and variable resistance exercises (Nautilus) performed 2 d.wk-1. PreTx body composition did not differ between groups. RESULTS At 2 months after Tx, fat-free mass was significantly decreased below baseline in both control (-3.4 +/- 2.1%) and ET groups (-4.3 +/- 2.4%). Fat mass was significantly increased at 2 months after Tx in both the control (+8.3 +/- 2.8%) and ET groups (+7.3 +/- 4.0%). Six months of ET restored fat-free mass to levels 3.9 +/- 2.1% greater (P < or = 0.05) than before Tx. Fat-free mass of the control group decreased progressively to levels that were 7 +/- 4.4% lower than preTx values (P < or = 0.05). Both groups increased knee extension, chest press, and lumbar extensor strength, but improvements in the ET group were four- to six-fold greater (P < or = 0.05). CONCLUSION Our results demonstrate that glucocorticoid-induced changes in body composition in HTR occur early after Tx. However, 6 months of specific ET restores fat-free mass to levels greater than before Tx and dramatically increases skeletal muscle strength. Resistance exercise, as part of a strategy to prevent steroid-induced myopathy, appears to be safe and should be initiated early after heart Tx.

Contracted plasma and blood volume in chronic heart failure

OBJECTIVES The purpose of this study was to determine if long-term pharmacotherapy mediated changes in intravascular plasma and blood volumes in patients with chronic heart failure (CHF). BACKGROUND Intravascular fluid volume expansion is an acute compensatory adaptation to ventricular dysfunction in patients with CHF. To our knowledge there are no reports on plasma and blood volume measures in clinically stable patients with CHF receiving standard pharmacotherapy. Such information may provide a better understanding of the clinical hallmarks of heart failure. METHODS Plasma volume (PV) and blood volume (BV) were measured in 12 patients (62.8 +/- 8.2 years old, 175.2 +/- 6.8 cm, 96.2 +/- 18.2 kg, peak oxygen consumption (VO2max) 15.2 +/- 3.3 ml/kg per min) with CHF secondary to coronary artery disease (left ventricular ejection fraction 31.2 +/- 9.7, New York Heart Association functional class 2.5 +/- 0.5) and seven healthy subjects (71.7 +/- 5.3 years old, 177.1 +/- 10.8 cm, 84.4 +/- 11.7 kg, VO2max 26.0 +/- 6.5 ml/kg per min) 3 to 4 h after eating and after supine rest using the Evans blue dye dilution technique. Venous blood samples were collected before blue dye infusion and analyzed for hematocrit (corrected 4% for trapped plasma and venous to whole body hematocrit ratio) and hemoglobin. RESULTS Hematocrit was 36.6 +/- 3.5% and 37.4 +/- 1.1%, and hemoglobin was 15.4 +/- 1.9 and 16.2 +/- 1.4 g/dl for patients with CHF and control subjects, respectively. Absolute PV was 3489.3 +/- 655.0 and 3728.7 +/- 813.2 ml, and absolute BV was 5,496.8 +/- 1,025.4 and 5,942.4 +/- 1,182.2 ml in patients with CHF and control subjects, respectively. Relative PV was 34.1 +/- 12.9 versus 44.5 +/- 9.0 ml/kg (p < or = 0.05), and relative BV was 58.5 +/- 12.3 versus 70.8 +/- 12.6 ml/kg (p < or = 0.05) in patients with CHF and control subjects, respectively. CONCLUSIONS Our data indicate significantly lower intravascular volumes in patients with CHF than in control subjects, indicating a deconditioned state or excessive diuresis, or both. The contracted PV and BV may contribute to exercise intolerance, shortness of breath and chronic fatigue, secondary to reduced cardiac output or regional blood flow, or both.

Stability and reproducibility of brachial artery flow-mediated dilation

PURPOSE Brachial artery flow-mediated dilation (BAFMD) is a noninvasive technique, which has been suggested as a potential means of identifying patients with early atherosclerosis and therefore has enormous clinical appeal. Despite this, the stability and reproducibility of this technique are not yet clear. Therefore, the purpose of this study was to establish the stability and reproducibility of BAFMD after 5 min of forearm occlusion and to produce power calculations to aid in clinical trial design. METHODS Twenty-six healthy volunteers underwent high-resolution ultrasonographic brachial artery assessments before, during, and after 5 min of forearm occlusion. The study design involved three scans on 2 d, performed by two ultrasonographers and analyzed by two readers. All subjects were tested between 7 and 11 a.m. after refraining from food and exercise. The nondominant arms were scanned, in longitudinal view, approximately 4 cm proximal to the olecranon process, in the anterior/medial plane. Blood draws were performed on each visit. The SAS MIXED restricted maximum likelihood (REML) procedure for an unbalanced design was used to calculate variance components and provide power calculations. RESULTS Average baseline artery diameter for all studies was 3.48 +/- 0.53 mm. This increased to 3.71 +/- 0.57 mm (6.58 +/- 4.15%) at peak dilation. Intraclass correlation coefficients (ICCC) for days, testers, and readers were 0.92, 0.94, and 0.90, respectively. To detect a difference in vasoreactivity of 60% (two-tailed), e.g., 5% vasodilation versus 8% vasodilation, at 90% power, 23 and 10 subjects would be required for cross-sectional and pre-post designs, respectively. CONCLUSIONS These data indicate adequate stability and reproducibility of the BAFMD technique under controlled conditions. Additionally, BAFMD appears useful to differentiate between groups, although its prognostic value for the examination of individuals is unclear.

Time course of improved flow-mediated dilation after short-term exercise training.

PURPOSE The purpose was to determine the influence of a unilateral localized short-term handgrip training protocol on brachial artery flow-mediated dilation (BAFMD) and to examine the time course of such changes. METHODS Fourteen healthy males (age: 26 +/- 5.7 yr) underwent high-resolution ultrasonographic brachial artery assessments before (V1), during (V2-V7), and at the end of 4 wk (V8) of 60% maximal voluntary contraction handgrip training (20 min.d-1, 5 d.wk-1) of the nondominant arm. RESULTS Before training resting diameters were similar between the trained (nondominant) and untrained (dominant) arms. A 2 (trained and untrained arms) x 2 (V1 and V8) repeated measure ANOVA revealed a significant main (P = 0.02 and P = 0.03) and interaction effect (P = 0.05 and P = 0.01) for the percent and absolute change in BAFMD. BAFMD improved 62% and 70%, respectively from V1 to V8, for the percent and absolute change. Subsequent linear orthogonal polynomial contrasts indicate both the percent and absolute change in BAFMD were statistically different at V2 (end of week 1 and 4 training days) from V1. These unilateral changes were not accompanied by changes in resting artery diameter, hemodynamic measures, hematological markers, and indices of heart rate variability suggesting the change may be locally mediated. CONCLUSIONS This study shows a localized short-term exercise-training program resulted in significant improvements in BAFMD in the trained arm compared with the untrained arm and suggests this occurred after only 4 d of training.

Ginseng Supplementation Does Not Enhance Healthy Young Adults’ Peak Aerobic Exercise Performance

OBJECTIVE To determine the short term effects (21 days) of 200 mg (7% standardized) Panax ginseng supplementation vs. placebo on peak aerobic exercise performance in healthy young adults, with unrestricted diets. METHODS Twenty men and eight women (age = 23.2 +/- 3.2 years, height = 175.8 +/- 8.6 cm; weight = 75.2 +/- 15.3 kg) were randomly assigned to either a Panax ginseng or placebo group for a period of 3 weeks in a double blind design. Prior to and following treatment the subjects performed a symptom limited graded exercise test on a Schwinn Airdyne ergometer. The data were analyzed using an analysis of variance. RESULTS No significant treatment effect was observed for the dependent variables of VO2, exercise time, workload, plasma lactate and hematocrit at peak levels, or for heart rate and rate of perceived exertion at 150 watts, 200 watts and peak. CONCLUSIONS The results of this study do not support an ergogenic effect on peak aerobic exercise performance following a 3-week supplementation period of 200 mg 7% Panax ginseng in healthy young adults with moderate exercise capacities and unrestricted diets.

Influence of short-term endurance exercise training on heart rate variability.

PURPOSE To examine the influence of 2 wk (eight sessions) of endurance training on cardiac autonomic modulation, as measured by heart rate variability (HRV). METHODS Twenty-four males (mean age: 23.1 yr) were randomized to an exercise (EX; N = 12) or control group (CT; N = 12). EX trained for eight sessions (4x wk-1, 40 min, 80-85% HRreserve) on a cycle ergometer. ECG tracings were collected during 5 min of paced breathing (12 breaths x min-1 (PB)), 5 min of spontaneous breathing (SB1), 5 min of 70 degrees head-up tilt (TILT), and a second 5-min period of spontaneous breathing (SB2). Data were collected before (test 1), during (tests 2-4), and 48 h after (test 5) the 2-wk period. HRV was reported as the standard deviation of RR intervals, and as natural logarithm of the normalized units (NU) of high- and low-frequency power (lnHF and lnLF). RESULTS EX exhibited a significant increase in peak oxygen consumption (8%). During PB and TILT conditions, ANOVA revealed a group x time interaction such that EX exhibited lower lnLFNU and lnLF/lnHF during test 5 compared with test 1. CONCLUSION These data suggest that eight endurance exercise-training sessions performed over 2 wk enhance the relative vagal modulation of the heart during PB and TILT, but not during SB.