A multimodality intervention to improve musculoskeletal health, function, metabolism, and well-being in spinal cord injury: study protocol for the FIT-SCI randomized controlled trial.

BACKGROUND: A spinal cord injury (SCI) is a devastating, life-changing event that has profoundly deleterious effects on an individual's health and well-being. Dysregulation of neuromuscular, cardiometabolic, and endocrine organ systems following an SCI contribute to excess morbidity, mortality and a poor quality of life. As no effective treatments currently exist for SCI, the development of novel strategies to improve the functional and health status of individuals living with SCI are much needed. To address this knowledge gap, the current study will determine whether a Home-Based Multimodality Functional Recovery and Metabolic Health Enhancement Program that consists of functional electrical stimulation of the lower extremity during leg cycling (FES-LC) plus arm ergometry (AE) administered using behavioral motivational strategies, and testosterone therapy, is more efficacious than FES-LC plus AE and placebo in improving aerobic capacity, musculoskeletal health, function, metabolism, and wellbeing in SCI. METHODS: This single-site, randomized, placebo-controlled, parallel group trial will enroll 88 community-dwelling men and women, 19 to 70 years of age, with cervical and thoracic level of SCI, ASIA Impairment Scale grade: A, B, C, or D, 6 months or later after an SCI. Participants randomized to the multimodality intervention will undergo 16 weeks of home-based FES-LC and AE training plus testosterone undecanoate. Testosterone undecanoate injections will be administered by study staff in clinic or by a visiting nurse in the participant's home. The control group will receive 16 weeks of home-based FES-LC and AE exercise plus placebo injections. The primary outcome of this trial is peak aerobic capacity, measured during an incremental exercise testing protocol. Secondary outcomes include whole body and regional lean and adipose tissue mass; muscle strength and power; insulin sensitivity, lipids, and inflammatory markers; SCI functional index and wellbeing (mood, anxiety, pain, life satisfaction and depressive symptoms); and safety. DISCUSSION: We anticipate that a multimodality intervention that simultaneously addresses multiple physiological impairments in SCI will result in increased aerobic capacity and greater improvements in other musculoskeletal, metabolic, functional and patient-reported outcomes compared to the control intervention. The findings of this study will have important implications for improving the care of people living with an SCI. TRIAL REGISTRATION: ClinicalTrials.gov :  ( NCT03576001 ). Prospectively registered: July 3, 2018.

Anabolic applications of androgens for functional limitations associated with aging and chronic illness.

Total and free testosterone concentrations decline progressively with advancing age because of defects at all levels of the hypothalamic-pituitary-testicular axis. Low total and bioavailable testosterone levels have been associated with decreased skeletal muscle mass, muscle strength, physical function, bone mineral density, and fracture risk, although these associations are weak. The risks and health benefits of long-term testosterone remain poorly understood. Physiologic testosterone replacement of young, androgen-deficient men and older men with low testosterone levels is associated with an increase in fat-free mass, grip strength, and fractional muscle protein synthesis, but we do not know whether testosterone replacement improves quadriceps strength, power, muscle fatigability, and physical function in older men, and whether it can reduce the risk of disability and falls. Testosterone replacement increases vertebral bone mineral density in young hypogonadal men and older men with low testosterone levels, but we do not know whether testosterone reduces fracture risk. Concerns about the potential adverse effects of testosterone on the prostate have encouraged the development of selective androgen receptor modulators that increase muscle mass while sparing the prostate.

Testosterone does not affect agrin cleavage in mobility-limited older men despite improvement in physical function.

In a subset of men, sarcopenia and physical dysfunction occur due to destabilization of the neuromuscular junction (NMJ), which is manifested by elevated serum concentrations of C-terminal agrin fragment (CAF). Testosterone administration improves physical function in some studies; however, its effects on serum circulating CAF concentrations remain unknown. Here we evaluate the effects of testosterone administration on circulating CAF levels in mobility-limited men with low testosterone aged 65 or older participating in the Testosterone in Older Men with Mobility Limitations (TOM) Trial. We analyzed the difference in change in serum CAF levels between testosterone and placebo groups, as well as its association with muscle strength and physical function. Association of change in serum CAF levels with serum total (TT) and free testosterone (FT) was also evaluated. Men randomized to testosterone experienced significant improvement in muscle strength and physical function (assessed by loaded stair-climbing power). However; testosterone administration was not associated with a reduction in serum CAF levels (effect size = -50.3 pm; 95% CI = -162.1 to 61.5 pm; p = 0.374); there was no association between changes in CAF levels with changes in TT (p = 0.670) or FT (p = 0.747). There was no association between changes in serum CAF levels with improvement in either muscle strength or stair-climbing power. In conclusion, testosterone treatment in mobility-limited older men with low to low-normal testosterone levels did not reduce serum CAF levels. Additionally, testosterone-induced improvements in muscle strength and physical function were not associated with changes in serum CAF concentrations. These findings suggest that improvement in physical function with testosterone replacement in older men with mobility limitations and elevated CAF levels is mediated by mechanisms other than stabilization of the NMJ.

Muscles of the trunk and pelvis are responsive to testosterone administration: data from testosterone dose-response study in young healthy men.

Testosterone dose-dependently increases appendicular muscle mass. However, the effects of testosterone administration on the core muscles of the trunk and the pelvis have not been evaluated. The present study evaluated the effects of testosterone administration on truncal and pelvic muscles in a dose-response trial. Participants were young healthy men aged 18-50 years participating in the 5α-Reductase (5aR) Trial. All participants received monthly injections of 7.5 mg leuprolide acetate to suppress endogenous testosterone production and weekly injections of 50, 125, 300, or 600 mg of testosterone enanthate and were randomized to receive either 2.5 mg dutasteride (5aR inhibitor) or placebo daily for 20 weeks. Muscles of the trunk and the pelvis were measured at baseline and the end of treatment using 1.5-Tesla magnetic resonance imaging. The dose effect of testosterone on changes in the psoas major muscle area was the primary outcome; secondary outcomes included changes in paraspinal, abdominal, pelvic floor, ischiocavernosus, and obturator internus muscles. The association between changes in testosterone levels and muscle area was also assessed. Testosterone dose-dependently increased areas of all truncal and pelvic muscles. The estimated change (95% confidence interval) of muscle area increase per 100 mg of testosterone enanthate dosage increase was 0.622 cm2 (0.394, 0.850) for psoas; 1.789 cm2 (1.317, 2.261) for paraspinal muscles, 2.530 cm2 (1.627, 3.434) for total abdominal muscles, 0.455 cm2 (0.233, 0.678) for obturator internus, and 0.082 cm2 (0.003, 0.045) for ischiocavernosus; the increase in these volumes was significantly associated with the changes in on-treatment total and free serum testosterone concentrations. In conclusion, core muscles of the trunk and pelvis are responsive to testosterone administration. Future trials should evaluate the potential role of testosterone administration in frail men who are predisposed to falls and men with pelvic floor dysfunction.

Effects of testosterone administration (and its 5-alpha-reduction) on parenchymal organ volumes in healthy young men: findings from a dose-response trial.

Animal data shows that testosterone administration increases the volume of some parenchymal organs. However, the effects of exogenous testosterone on solid abdominal organs in humans remain unknown. The present study evaluated the effects of testosterone administration on the volume of liver, spleen and kidneys in a dose-response trial. Young healthy men aged 18-50 years participating in the 5α-Reductase (5aR) Trial. All participants received monthly injections of 7.5 mg leuprolide acetate to suppress endogenous testosterone secretion and weekly injections of 50, 125, 300 or 600 mg of testosterone enanthate, and were randomized to receive either 2.5 mg dutasteride (5 α-reductase inhibitor) or placebo daily for 20 weeks. Liver, spleen and kidney volumes were measured at baseline and the end of treatment using 1.5-Tesla magnetic resonance imaging. The dose-effect of testosterone on changes in the volume of parenchymal organs was evaluated by linear regression model. The association between changes in total testosterone (TT) levels and changes in organ volumes were assessed. Testosterone administration increased liver volume dose-dependently (17.4 cm3 per 100 mg of weekly testosterone enanthate; p = 0.031); the increase in liver volume was positively associated with changes in TT levels (R2  = 0.08, p = 0.024). A dose-dependent, but non-significant, increase in kidney volumes was also seen. Inclusion of dutasteride use into the models showed an independent association of randomization to dutasteride group with liver volume increase. In conclusion, Testosterone administration increased the liver volume in a dose-dependent manner. The potential changes in parenchymal organs should be considered when interpreting apparent changes in lean mass in response to anabolic interventions.

Effects of testosterone replacement in human immunodeficiency virus-infected women with weight loss.

The objective of this study was to determine whether physiological testosterone replacement increases fat-free mass (FFM) and muscle strength and contributes to weight maintenance in HIV-infected women with relative androgen deficiency and weight loss. Fifty-two HIV-infected, medically stable women, 18-50 yr of age, with more than 5% weight loss over 6 months and testosterone levels below 33 ng/dl were randomized into this double-blind, placebo-controlled trial of 24-wk duration. Subjects in the testosterone group applied testosterone patches twice weekly to achieve a nominal delivery of 300 mug testosterone over 24 h. Data were evaluable for 44 women. Serum average total and peak testosterone levels increased significantly in the testosterone group, but did not change in the placebo group. However, there were no significant changes in FFM (testosterone, 0.7 +/- 0.4 kg; placebo, 0.3 +/- 0.4 kg), fat mass (testosterone, 0.3 +/- 0.7 kg; placebo, 0.6 +/- 0.7 kg), or body weight (testosterone, 1.0 +/- 0.9 kg; placebo, 0.9 +/- 0.8 kg) between the two treatment groups. There were no significant changes in leg press strength, leg power, or muscle fatigability in either group. Changes in quality of life, sexual function, cognitive function, and Karnofsky performance scores did not differ significantly between the two groups. High-density lipoprotein cholesterol levels decreased significantly in the testosterone group. The patches were well tolerated. We conclude that physiological testosterone replacement was safe and effective in raising testosterone levels into the mid to high normal range, but did not significantly increase FFM, body weight, or muscle performance in HIV-infected women with low testosterone levels and mild weight loss. Additional studies are needed to fully explore the role of androgens in the regulation of body composition in women.

The effects of supraphysiological doses of testosterone on angry behavior in healthy eugonadal men--a clinical research center study.

UNLABELLED: Anecdotal reports of "roid rage" and violent crimes by androgenic steroid users have brought attention to the relationship between anabolic steroid use and angry outbursts. However, testosterone effects on human aggression remain controversial. Previous studies have been criticized because of the low androgen doses, lack of placebo control or blinding, and inclusion of competitive athletes and those with preexisting psychopathology. To overcome these pitfalls, we used a double-blind, placebo-controlled design, excluded competitive athletes and those with psychiatric disorders, and used 600 mg testosterone enanthate (TE)/week. Forty-three eugonadal men, 19-40 yr, were randomized to 1 of 4 groups: Group I, placebo, no exercise; Group II, TE, no exercise; Group III, placebo, exercise; Group IV, TE plus exercise. Exercise consisted of thrice weekly strength training sessions. The Multi-Dimensional Anger Inventory (MAI), which includes 5 different dimensions of anger (inward anger, outward anger, anger arousal, hostile outlook, and anger eliciting situations), and a Mood Inventory (MI), which includes items related to mood and behavior, were administered to subjects before, during, and after the 10 week intervention. The subject's significant other (spouse, live-in partner, or parent) also answered the same questions about the subject's mood and behavior (Observer Mood Inventory, OMI). No differences were observed between exercising and nonexercising and between placebo and TE treated subjects for any of the 5 subdomains of MAI. Overall there were no significant changes in MI or OMI during the treatment period in any group. CONCLUSION: Supraphysiological doses of testosterone, when administered to normal men in a controlled setting, do not increase angry behavior. These data do not exclude the possibility that still higher doses of multiple steroids might provoke angry behavior in men with preexisting psychopathology.

Testosterone replacement increases fat-free mass and muscle size in hypogonadal men.

Testosterone-induced nitrogen retention in castrated male animals and sex-related differences in the size of the muscles in male and female animals have been cited as evidence that testosterone has anabolic effects. However, the effects of testosterone on body composition and muscle size have not been rigorously studied. The objective of this study was to determine the effects of replacement doses of testosterone on fat-free mass and muscle size in healthy hypogonadal men in the setting of controlled nutritional intake and exercise level. Seven hypogonadal men, 19-47 yr of age, after at least a 12-week washout from previous androgen therapy, were treated for 10 weeks with testosterone enanthate (100 mg/week) by im injections. Body weight, fat-free mass measured by underwater weighing and deuterated water dilution, and muscle size measured by magnetic resonance imaging were assessed before and after treatment. Energy and protein intake were standardized at 35 Cal/kg.day and 1.5 g/kg.day, respectively. Body weight increased significantly from 79.2 +/- 5.6 to 83.7 +/- 5.7 kg after 10 weeks of testosterone replacement therapy (weight gain, 4.5 +/- 0.6 kg; P = 0.0064). Fat-free mass, measured by underwater weighing, increased from 56.0 +/- 2.5 to 60.9 +/- 2.2 kg (change, +5.0 +/- 0.7 kg; P = 0.0004), but percent fat did not significantly change. Similar increases in fat-free mass were observed with the deuterated water method. The cross-sectional area of the triceps arm muscle increased from 2421 +/- 317 to 2721 +/- 239 mm2 (P = 0.045), and that of the quadriceps leg muscle increased from 7173 +/- 464 to 7720 +/- 454 mm2 (P = 0.0427), measured by magnetic resonance imaging. Muscle strength, assessed by one repetition maximum of weight-lifting exercises increased significantly after testosterone treatment. L-[1-13C]Leucine turnover, leucine oxidation, and nonoxidative disappearance of leucine did not significantly change after 10 weeks of treatment. There was no significant change in hemoglobin, hematocrit, creatinine, and transaminase levels. Replacement doses of testosterone increase fat-free mass and muscle size and strength in hypogonadal men. Whether androgen replacement in wasting states characterized by low testosterone levels will have similar anabolic effects remains to be studied.

Effects of testosterone replacement with a nongenital, transdermal system, Androderm, in human immunodeficiency virus-infected men with low testosterone levels.

Although weight loss associated with human immunodeficiency virus (HIV) infection is multifactorial in its pathogenesis, it has been speculated that hypogonadism, a common occurrence in HIV disease, contributes to depletion of lean tissue and muscle dysfunction. We, therefore, examined the effects of testosterone replacement by means of Androderm, a permeation-enhanced, nongenital transdermal system, on lean body mass, body weight, muscle strength, health-related quality of life, and HIV-disease markers. We randomly assigned 41 HIV-infected, ambulatory men, 18-60 yr of age, with serum testosterone levels below 400 ng/dL, to 1 of 2 treatment groups: group I, two placebo patches (n = 21); or group II, two testosterone patches designed to release 5 mg testosterone over 24 h. Eighteen men in the placebo group and 14 men in the testosterone group completed the 12-week treatment. Serum total and free testosterone and dihydrotestosterone levels increased, and LH and FSH levels decreased in the testosterone-treated, but not in the placebo-treated, men. Lean body mass and fat-free mass, measured by dual energy x-ray absorptiometry, increased significantly in men receiving testosterone patches [change in lean body mass, +1.345 +/- 0.533 kg (P = 0.02 compared to no change); change in fat-free mass, +1.364 +/- 0.525 kg (P = 0.02 compared to no change)], but did not change in the placebo group [change in lean body mass, 0.189 +/- 0.470 kg (P = NS compared to no change); change in fat-free mass, 0.186 +/- 0.470 kg (P = NS compared to no change)]. However, there was no significant difference between the 2 treatment groups in the change in lean body mass. The change in lean body mass during treatment was moderately correlated with the increment in serum testosterone levels (r = 0.41; P = 0.02). The testosterone-treated men experienced a greater decrease in fat mass than those receiving placebo patches (P = 0.04). There was no significant change in body weight in either treatment group. Changes in overall quality of life scores did not correlate with testosterone treatment; however, in the subcategory of role limitation due to emotional problems, the men in the testosterone group improved an average of 43 points of a 0-100 possible score, whereas those in the placebo group did not change. Red cell count increased in the testosterone group (change in red cell count, +0.1 +/- 0.1 10(12)/L) but decreased in the placebo group (change in red cell count, -0.2 +/- 0.1 10(12)/L). CD4+ and CD8+ T cell counts and plasma HIV copy number did not significantly change during treatment. Serum prostate-specific antigen and plasma lipid levels did not change in either treatment group. Testosterone replacement in HIV-infected men with low testosterone levels is safe and is associated with a 1.35-kg gain in lean body mass, a significantly greater reduction in fat mass than that achieved with placebo treatment, an increased red cell count, and an improvement in role limitation due to emotional problems. Further studies are needed to assess whether testosterone supplementation can produce clinically meaningful changes in muscle function and disease outcome in HIV-infected men.

Proof of the effect of testosterone on skeletal muscle.

In spite of the widespread abuse of androgenic steroids by athletes and recreational body-builders, the effects of these agents on athletic performance and physical function remain poorly understood. Experimentally induced androgen deficiency is associated with a loss of fat-free mass; conversely, physiologic testosterone replacement of healthy, androgen-deficient men increases fat-free mass and muscle protein synthesis. Testosterone supplementation of HIV-infected men with low testosterone levels and of older men with normally low testosterone concentrations also increases muscle mass. However, we do not know whether physiologic testosterone replacement can improve physical function and health-related quality of life, and reduce the risk of falls and disability in older men or those with chronic illness. Testosterone increases maximal voluntary strength in a dose-dependent manner and thus might improve performance in power-lifting events. However, testosterone has not been shown to improve performance in endurance events. The mechanisms by which testosterone increases muscle mass are not known, but probably involve alterations in the expression of multiple muscle growth regulators.

12-year-old male with Elejalde syndrome (neuroectodermal melanolysosomal disease).

Neuroectodermal melanolysosomal disease, also known as Elejalde syndrome, is a rare syndrome characterized by silvery hair, pigment abnormalities, and profound central nervous system dysfunction. It is similar to the Chediak-Higashi and Griscelli syndromes, although these syndromes are associated with severe immunologic dysfunction. We report on a 12-year-old male with Elejalde syndrome and compare the Elejalde, Chediak-Higashi, and Griscelli syndromes.

Mediation of reduced ventilatory response to exercise after endurance training.

To investigate the mechanism by which ventilatory (VE) demand is modulated by endurance training, 10 normal subjects performed cycle ergometer exercise of 15 min duration at each of four constant work rates. These work rates represented 90% of the anaerobic threshold (AT) work rate and 25, 50, and 75% of the difference between maximum O2 consumption and AT work rates for that subject (as determined from previous incremental exercise tests). Subjects then underwent 8 wk of strenuous cycle ergometer exercise for 45 min/day. They then repeated the four constant work rate tests at work rates identical to those used before training. During tests before and after training, VE and gas exchange were measured breath by breath and rectal temperature (Tre) was measured continuously. A venous blood sample was drawn at the end of each test and assayed for lactate (La), epinephrine (EPI), and norepinephrine (NE). We found that the VE for below AT work was reduced minimally by training (averaging 3 l/min). For the above AT tests, however, training reduced VE markedly, by an average of 7, 23, and 37 l/min for progressively higher work rates. End-exercise La, NE, EPI, and Tre were all lower for identical work rates after training. Importantly, the magnitude of the reduction in VE was well correlated with the reduction in end-exercise La (r = 0.69) with an average decrease of 5.8 l/min of VE per milliequivalent per liter decrease in La. Correlations of VE with NE, EPI, and Tre were much less strong (r = 0.49, 0.43, and 0.15, respectively).

Effect of endurance training on possible determinants of VO2 during heavy exercise.

When moderate exercise begins, O2 uptake (VO2) reaches a steady state within 3 min. However, with heavy exercise, VO2 continues to rise beyond 3 min (VO2 drift). We sought to identify factors contributing to VO2 drift. Ten young subjects performed cycle ergometer tests of 15 min duration for each of four constant work rates, corresponding to 90% of the anaerobic threshold (AT) and 25, 50, and 75% of the difference between maximum VO2 (VO2 max) and AT for that subject. Time courses of VO2, minute ventilation (VE), and rectal temperature were recorded. Blood lactate, norepinephrine, and epinephrine were measured at the end of exercise. Eight weeks of cycle ergometer endurance training improved average VO2 max by 15%. Subjects then performed four tests identical to pretraining studies. For the above AT tests, training reduced VO2 drift substantially; reduction in each of the possible mediators we measured was also demonstrated. The training-induced decrease in VO2 drift was well correlated with decreases in end exercise lactate and less well correlated with the drift in VE seen at above AT work rates. The training-induced reduction in VO2 drift was not significantly correlated with attenuation of rectal temperature rise or decrease in end-exercise level of the catecholamines. Thus the slow rise in VO2 during heavy exercise seems linked to lactate, though a component dictated by the work of breathing cannot be ruled out.

Treadmill exercise duration and dyspnea recovery time in chronic obstructive pulmonary disease: effects of oxygen breathing and repeated testing.

Oxygen supplementation is known to improve exercise capacity in patients with chronic obstructive pulmonary disease (COPD). Although some COPD patients use oxygen after exercise to relieve dyspnea, the effect of oxygen during recovery from exercise is not clearly understood. Exercise duration and dyspnea recovery time were studied in 18 patients with stable COPD. Patients exercised at a constant submaximal work rate on a treadmill ergometer until they no longer wished to continue. Oxygen, room air and compressed air were randomly administered in three consecutive post-exercise recovery periods. Dyspnea was scored on a 100 mm visual analog scale at 30 s intervals until return to baseline. An additional 20 minute post-recovery resting period was allowed between each test. No significant differences were found in dyspnea recovery time breathing oxygen (271 s), room air (290 s) or compressed air (311 s) When the groups were sorted by sequence of testing, there was a highly significant increase in recovery time (208 s, 307 s and 358 s for the first, second and third tests; P < 0.005) and a non-statistically significant decrease in exercise duration (89 s, 79 s and 76 s). Post-exercise oxygen supplementation had no effect on dyspnea recovery time in these COPD patients. Repeated bouts of exercise increased dyspnea recovery time and tended to decrease exercise duration. These findings suggest that, despite recovery of symptoms, physiological recovery from prior exercise is incomplete.

Exercise in chronic pulmonary disease: resistance exercise prescription.

Resistance exercise training has received relatively little attention as a means to reduce the muscle dysfunction and ensuing exercise intolerance seen in chronic pulmonary diseases. To date, only a few studies have examined the characteristics of skeletal muscle function or its responsiveness to strength training in patients with chronic respiratory diseases. It is clear from these studies, however, that peripheral muscle, particularly muscles of ambulation, are weak in patients with lung disease, exhibiting effort-dependent strength scores that are 70--80% of these measures in age-matched healthy subjects. The degree to which this dysfunction is accounted for by deconditioning, disease-related myopathy, or other causes is unclear. It is evident, however, that patients with chronic respiratory diseases can acquire and maintain substantial improvements in skeletal muscle function, physical function, and quality of life through participation in a well-structured program of resistance exercise training. Despite the positive, albeit limited, evidence that skeletal muscle dysfunction may be improved with resistance training, no clear guidelines are available for this purpose. This review discusses the skeletal muscle dysfunction that accompanies chronic respiratory disease and presents strategies for resistance exercise training that may be considered as part of pulmonary rehabilitation. These strategies are derived from the successful outcomes noted in studies using resistance training in patients with COPD as well as on extrapolations from extant guidelines used to develop strength, power, and endurance in healthy individuals.

Accurate prediction of VO2max in cycle ergometry.

Numerous equations exist for predicting VO2max from the duration (an analog of maximal work rate, Wmax) of a treadmill graded exercise test (GXT). Since a similar equation for cycle ergometry (CE) was not available, we saw the need to develop such an equation, hypothesizing that CE VO2max could be accurately predicted due to its more direct relationship with W. Thus, healthy, sedentary males (N = 115) and females (N = 116), aged 20-70 yr, were given a 15 W.min-1 CE GXT. The following multiple linear regression equations which predict VO2max (ml.min-1) from the independent variables of Wmax (W), body weight (kg), and age (yr) were derived from our subjects: Males: Y = 10.51 (W) + 6.35 (kg) - 10.49 (yr) + 519.3 ml.min-1; R = 0.939, SEE = 212 ml.min-1. Females: Y = 9.39 (W) + 7.7 (kg) - 5.88 (yr) + 136.7 ml.min-1; R = 0.932, SEE = 147 ml.min-1 Using the 95% confidence limits as examples of worst case errors, our equations predict VO2max to within 10% of its true value. Internal (double cross-validation) and external cross-validation analyses yielded r values ranging between 0.920 and 0.950 for the male and female regression equations. These results indicate that use of the equations generated in this study for a 15 W.min-1 CE GXT provides accurate estimates of VO2max.

Evaluation of blood lactate elevation as an intensity criterion for exercise training.

We sought to determine whether exercise intensities not elevating blood lactate produce alterations in physiological responses to exercise associated with training. Twenty-seven sedentary young men performed five cycle ergometer training sessions.wk-1 for 5 wk. Training power outputs were randomized to power outputs corresponding to either 80% of the lactic acidosis threshold (LAT), 25% delta or 50% delta (where delta is the difference between LAT and peak VO2 power outputs estimated from incremental exercise tests). Exercise sessions were 30 min for the 50% delta group and were proportionately longer for other groups, so that total work did not vary among groups. Before and after training, subjects exercised for 15 min (or to tolerance) at pretraining 80% LAT, 25% delta, 50% delta, and 75% delta power outputs. Continuous O2 uptake, CO2 output, ventilation and heart rate, and end-exercise blood lactate, norepinephrine, and epinephrine were measured. For the 80% LAT group, posttraining end-exercise values for the 75% delta test were significantly lower for each of these variables. There were similar reductions in each variable in all three training groups; no significant differences among groups were seen. Thus, in healthy subjects exercise which does not elevate blood lactate alters constant power output responses as effectively as exercise which elevates lactate, provided that total training work is the same.

On issues of confidence in determining the time constant for oxygen uptake kinetics.

BACKGROUND: TauVO(2 )at the onset of constant work rate (CWR) exercise is a variable of aerobic fitness that shortens with physical training and lengthens with cardiopulmonary disease. Determination of tauVO(2) with sufficiently high confidence has typically required multiple exercise transitions limiting its clinical application. OBJECTIVES: To design a protocol to determine tauVO(2) reliably but simply. METHODS: On each of three days, five healthy men performed two CWR tests on a cycle ergometer below the metabolic threshold (VO(2)theta) for blood lactate accumulation as determined by gas exchange measurements followed by an incremental work rate (IWR) test. TauVO(2) was determined (a) from the on-transit (on-tauVO(2)) and off-transit (off-tauVO(2)) of six CWR tests both individually and superimposed, using non-linear regression with a monoexponential model, and (b) by geometric analysis of the IWR tests (ramp-tauVO(2)). RESULTS: Group means (SD) were: VO(2)max 3.84 (0.44) litres/min, VO(2)theta 1.88 (0.23) litres/min, steady state exercise VO(2) 1.67 (0.07) litres/min, on-tauVO(2) 38.0 (5.3) seconds, off-tauVO(2) 39.0 (4.3) seconds, and ramp-tauVO(2) 60.8 (15.4) seconds. On-tauVO(2) correlated with off-tauVO(2) (r = 0.87), VO(2)max (r = -0.73), and VO(2)theta (r = 0.89). The pooled mean tauVO(2) from six superimposed tests agreed with the arithmetic grand mean of the six tests. CONCLUSIONS: The average of on-tauVO(2) and off-tauVO(2) fell within the 95% confidence interval of the pooled mean by the second test. Ramp-tauVO(2) was longer and less reproducible. These findings support the use of both on- and off-transit data for the determination of tauVO(2), an approach that reduces the number of transitions necessary for accurate determination of tauVO(2), potentially enhancing its clinical application.

Essential Hypertension and Exercise.

In brief: Responses to a questionnaire given to physicians and clinic directors in the Salt Lake City area indicated the current practices in treating essential hypertension. The most common treatment was step-care drug therapy, although some used exercise as a treatment modality. The authors concluded that: (1) the value of exercise in treating hypertension is not completely understood; (2) the undesirable side effects of drug therapy suggest a closer examination of nonpharmacological treatment; (3) borderline or labile hypertensives are often not treated without specific indications; and (4) exercise physiologists might be helpful to physicians who want to use exercise therapy for their hypertensive patients.