Health-Promoting Effects of Serial vs. Integrated Combined Strength and Aerobic Training.

Combined strength and aerobic training programs are widely used for improving markers of physical fitness and health. We compared the efficiency of a serial and an integrated combined training program on health and overall fitness in middle-aged females. 54 females (46.7±4.5yrs) were assigned to a serial (SCG) or an integrated (ICG) combined training group or to a control group (CG). The SCG and ICG performed a 3-month training combining aerobic dance and calisthenics. The 2 training programs differ in the sequence of aerobic and strength exercises. SCG performed the strength exercises prior to aerobic; in ICG, the aerobic and strength exercises were altered in a predetermined order. Body composition/circumferences, blood pressure, respiratory function, flexibility, balance, muscle strength/endurance, power and aerobic capacity were measured before and after training. SCG and ICG significantly increased muscle strength and endurance, power, aerobic capacity, flexibility, balance, fat-free mass and respiratory function (p<0.001-0.05), while significant reductions were observed for blood pressure, heart rate and body fat/circumferences (p<0.001-0.05). However, there were no significant differences between SCG and ICG after training. Serial and integrated combined training programs confer analogous adaptations and can be used interchangeably for counteracting the detrimental effects of sedentary lifestyle on indices of physical fitness and health.

Oxygen Delivery and Muscle Deoxygenation during Continuous, Long- and Short-Interval Exercise.

This study compared the O2 delivery (a central determinant of VO2) and muscle deoxygenation (reflecting a peripheral determinant of VO2) during intense continuous, long-interval, and short-interval exercise protocols. Twelve young men completed the 3 protocols with equal overall effort. Simultaneous and continuous recordings of central hemodynamics, muscle oxygenation/deoxygenation and VO2 were performed. Peak responses for stroke volume and peripheral resistance did not differ among protocols, whereas peak cardiac output and VO2 were higher in long-interval vs. continuous and short-interval protocols with inactive rest phases (p<0.05). The average responses for all central parameters were higher in continuous and long-interval vs. short-interval exercise (p<0.05); average VO2 and exercise-time above 80% VO2max were also higher in continuous and long-interval vs. short-interval protocol (p<0.05). Muscle de-oxygenation (↑Δdeoxyhemoglobin,↓Δoxyhemoglobin, ↓muscle O2-saturation), as well as the mismatch of O2 delivery and utilization (Δdeoxyhemoglobin/VO2) were remarkably alike among protocols. In conclusion, all 3 protocols resulted in a great activation of central and peripheral determinants of VO2. When performed with equal overall effort, the intense continuous and interval modalities reveal similarities in muscle O2-utilization response, but differences in central hemodynamic and VO2 responses. Intense continuous and long-interval protocols exert a more commanding role on the cardiovascular system and VO2 response compared to short-interval exercise with inactive rest phases.

Reliability of concentric and eccentric strength of hip abductor and adductor muscles in young soccer players.

The concentric and eccentric strength profile and muscular balance of the hip joint are important parameters for success in soccer. This study evaluated the reliability for the assessment of hip abduction and adduction isokinetic strength over a range of angular velocities (30 and 90°/s) and types of muscular actions (concentric and eccentric) in young soccer players. The reliability for the assessment of reciprocal (conventional and functional) and bilateral torque ratios was also examined. Fifteen male soccer players (15±1 years) performed two sessions, separated by three days. The testing protocol consisted of five maximal concentric and eccentric hip abductions and adductions of both legs at angular velocities of 30°/s and 90°/s. The peak torque was evaluated in young soccer players using an isokinetic dynamometer (Cybex Norm), and the reciprocal strength ratios (conventional and functional) and bilateral ratios (non-preferred to preferred leg ratios) were calculated. The test-retest reliability for the assessment of peak torque (ICC = 0.71-0.92) and of reciprocal muscle group ratios (ICC = 0.44-0.87) was found to be moderate to high. Bilateral torque ratios exhibited low to moderate reliability (ICC = 0.11-0.64). In conclusion, isokinetic strength of hip abductor and adductor muscles and the conventional and functional strength ratios can be reliably assessed in young soccer players, especially at low angular velocities. The assessment, however, of bilateral strength ratios for hip abductor/adductor muscles should be interpreted with more caution.

Differences in cerebral oxygenation during exercise in patients with idiopathic pulmonary fibrosis with and without exertional hypoxemia: does exercise intensity matter?

INTRODUCTION AND OBJECTIVES: Patients with idiopathic pulmonary fibrosis (IPF) present respiratory derangements at rest and during exercise, accompanied by exercise intolerance. Some patients may develop profound exertional desaturation even without resting hypoxemia. Evidence suggests the involvement of reduced cerebral-oxygenation in exercise intolerance. We aimed to examine (i) differences in cerebral-oxygenation during exercise between IPF patients with and without isolated exertional desaturation, (ii) whether the impairments in cerebral-oxygenation are detected at similar exercise intensity, and (iii) correlations between cerebral-oxygenation indices, disease severity, and 6-min walk test (6MWT). MATERIALS AND METHODS: Patients with IPF (n = 24; 62.1 ± 9.3 years) without resting hypoxemia underwent cardiopulmonary exercise testing (CPET) with cerebral-oxygenation monitoring via near-infrared-spectroscopy (NIRS). Βased on their pulse-oxymetry saturation (SpO2) during CPET, patients were divided into the "exertional-desaturators" group (SpO2nadir≤89% and ≥6% drop in SpO2) and the "non-exertional-desaturators" group (SpO2nadir≥90% and ≤5% drop). RESULTS: During CPET, the "exertional-desaturators" group exhibited lower oxygenated-hemoglobin (-0.67 ± 1.48 vs. 0.69 ± 1.75 µmol/l; p < 0.05) and higher deoxygenated-hemoglobin (1.67 ± 1.13 vs. 0.17 ± 0.62 µmol/l; p < 0.001) than the "non-exertional-desaturators" group. A different pattern (p < 0.01) in cerebral-oxygenation responses was observed in the two groups. In exertional-desaturators oxygenated-hemoglobin declined below baseline even at low/moderate-intensity exercise (p < 0.05), whereas, in non-exertional-desaturators cerebral-oxygenation declined (p < 0.05) at high-intensity exercise. Cerebral-NIRS indices correlated (p < 0.05) with CPET-duration, dyspnea, diffusion capacity, and 6MWT. CONCLUSIONS: During incremental exercise, patients with IPF and exertional desaturation present a significant decline in cerebral-oxygenation even during low-intensity exercise. Our findings support the implementation of longer-duration rehabilitation programs in IPF so that lower intensity exercise can be applied at the initial stages. (NCT03683082).

Muscle perfusion of posterior trunk and lower-limb muscles at rest and during upper-limb exercise in spinal cord-injured and able-bodied individuals.

STUDY DESIGN: Nonrandomized-controlled trial. OBJECTIVES: To assess muscle perfusion at rest and during arm-cranking exercise (ACE) in upper and lower posterior trunk and vastus lateralis (VL) muscles in individuals with spinal cord injury (SCI) and controls (C). SETTING: Exercise Physiology-Biochemistry Laboratory. METHODS: Eight SCI with thoracic lesion and eight C received injections of radioactive tracer to trapezius (TRAP), latissimus dorsi (LAT) and VL. Radioactive counts were recorded with a γ-camera for 10 min at rest and during ACE (60% VO(2max) for 20 min). Time-count curves were generated and the isotope clearance rate, expressed as half-life time (T(1/2),min), was calculated to assess muscle perfusion. RESULTS: Resting T(1/2) was lower in TRAP and LAT vs VL (P<0.05) in SCI, however, there were no differences among muscles in C. Arm-cranking increased (P<0.001) the isotope clearance in TRAP and LAT in SCI and C, whereas no effect was found on T(1/2) in VL in both groups. T(1/2) was longer (P<0.05) in SCI vs C in VL at rest and during ACE, whereas there were no differences between groups in posterior trunk muscles. CONCLUSIONS: Resting muscle perfusion was reduced in the paralyzed limbs of SCI compared with C, whereas there was no evidence of impaired microcirculation in upper and lower back muscles in SCI. Although ACE did not induce a hyperemic response in VL, it increased hyperemia in upper and lower posterior trunk muscles in SCI, suggesting beneficial effects of this type of activity on muscle microvasculature in this region.

Altered hemodynamic regulation and reflex control during exercise and recovery in obese boys.

The aims of the present study were to assess in obese and lean boys 1) the hemodynamic responses and baroreflex sensitivity (BRS) to isometric handgrip exercise (HG) and recovery and 2) the muscle metaboreflex-induced blood pressure response and the variables that determine this response. Twenty-seven boys (14 obese and 13 lean boys, body mass index: 29.2 ± 0.9 vs. 18.9 ± 0.3 kg/m(2), respectively) participated. The testing protocol involved 3 min of baseline, 3 min of HG (30% maximum voluntary contraction), 3 min of circulatory occlusion, and 3 min of recovery. The same protocol was repeated without occlusion. At baseline, no differences were detected between groups in beat-to-beat arterial pressure (AP), heart rate (HR), and BRS; however, obese boys had higher stroke volume and lower total peripheral resistance than lean boys (P < 0.05). During HG, lean boys exhibited higher HR and lower BRS compared with their obese counterparts. In lean boys, BRS decreased during HG compared with baseline, whereas in obese boys, it was not significantly modified. In lean boys, TPR was elevated during HG and declined after exercise, whereas in obese boys, TPR did not significantly decrease after exercise cessation. In the postexercise period, BRS in lean boys returned to baseline, whereas an overshoot was observed in obese boys. Postexercise BRS was correlated with body mass index (R = 0.56, P < 0.05). Although the metaboreflex-induced increase in AP was similar between obese and lean children, it was achieved via different mechanisms: in lean children, total peripheral resistance was the main contributor to AP maintenance during the metaboreflex, whereas in obese children, stroke volume significantly contributed to AP maintenance during the metaboreflex. In conclusion, obese normotensive children demonstrated altered cardiovascular hemodynamics and reflex control during exercise and recovery.

Adaptations to endurance training depend on exercise-induced oxidative stress: exploiting redox interindividual variability.

AIM: The aim of this study was to reveal the role of reactive oxygen and nitrogen species (RONS) in exercise adaptations under physiological in vivo conditions and without the interference from other exogenous redox agents (e.g. a pro-oxidant or antioxidant). METHODS: We invented a novel methodological set-up that exploited the large redox interindividual variability in exercise responses. More specifically, we used exercise-induced oxidative stress as the 'classifier' measure (i.e. low, moderate and high) and investigated the physiological and redox adaptations after a 6-week endurance training protocol. RESULTS: We demonstrated that the group with the low exercise-induced oxidative stress exhibited the lowest improvements in a battery of classic adaptations to endurance training (VO2 max, time trial and Wingate test) as well as in a set of redox biomarkers (oxidative stress biomarkers and antioxidants), compared to the high and moderate oxidative stress groups. CONCLUSION: The findings of this study substantiate, for the first time in a human in vivo physiological context, and in the absence of any exogenous redox manipulation, the vital role of RONS produced during exercise in adaptations. The stratification approach, based on a redox phenotype, implemented in this study could be a useful experimental strategy to reveal the role of RONS and antioxidants in other biological manifestations as well.

The effects of resisted sled-pulling sprint training on acceleration and maximum speed performance.

AIM: The purpose of the present study was to examine the effects of resisted (RS) and un-resisted (US) sprint training programs on acceleration and maximum speed performance. METHODS: Twenty-two male students (age 20.1+/-1.9 y, height 1.78+/-7 cm, and weight 73+/-2 kg) completed RS (n=11) or US (n=11) sprint training programs. The RS group followed a sprint-training program with 5 kg sled pulling and the US group followed a similar sprint-training program without sled pulling. The training program consisted of 4x20 m and 4x50 m maximal runs, and was applied 3 times/week for 8 weeks. Before and after the training programs the subjects performed a 50 m run and the running velocity of 0(-1)0 m, 10(-2)0 m, 20-40 m and 40-50 m was measured. In addition, stride length and stride frequency were evaluated at the 3(rd) stride in acceleration phase and between 42-47 m in maximum speed phase. RESULTS: The RS improved running velocity in the run sections 0(-1)0 m and 0(-2)0 m, while in US group the running velocity in all run sections in acceleration phase remained unchanged (p>0.05). In contrast, RS training had no effect on running velocity in maximum speed phase, whereas US improved running velocity in 20-40 m, 40-50 m, and 20-50 m run sections (p<0.05). Stride rate increased only after RS in acceleration phase (+7.1+/-2.9%; p<0.05), whereas stride length increased only after US in maximum speed phase (+5.5+/-2.5%; p<0.05). CONCLUSION: Sprint training with 5 kg sled pulling for 8 weeks improves acceleration performance (0(-2)0), while un-resisted sprint training improves performance in maximum speed phase (20-40) in non-elite athletes. It appears that each phase of sprint run demands a specific training approach.

Serum leptin responses after acute resistance exercise protocols.

This study examined the acute effects of maximum strength (MS), muscular hypertrophy (MH), and strength endurance (SE) resistance exercise protocols on serum leptin. Ten young lean men (age = 23 +/- 4 yr; body weight = 79.6 +/- 5.2 kg; body fat = 10.2 +/- 3.9%) participated in MS [4 sets x 5 repetitions (reps) at 88% of 1 repetition maximum (1 RM) with 3 min of rest between sets], MH (4 sets x 10 reps at 75% of 1 RM with 2 min of rest between sets), SE (4 sets x 15 reps at 60% of 1 RM with 1 min of rest between sets), and control (C) sessions. Blood samples were collected before and immediately after exercise and after 30 min of recovery. Serum leptin at 30 min of recovery exhibited similar reductions from baseline after the MS (-20 +/- 5%), MH (-20 +/- 4%), and SE (-15 +/- 6%) protocols that were comparable to fasting-induced reduction in the C session (-12 +/- 3%) (P < 0.05). Furthermore, no differences were found in serum leptin among the MS, MH, SE, and C sessions immediately after exercise and at 30 min of recovery (P > 0.05). Cortisol was higher (P < 0.05) after the MH and SE protocols than after the MS and C sessions. Glucose and growth hormone were higher (P < 0.05) after exercise in the MS, MH, and SE protocols than after the C session. In conclusion, typical resistance exercise protocols designed for development of MS, MH, and SE did not result in serum leptin changes when sampled immediately or 30 min postexercise.

Clinical pharmacology of rapacuronium bromide, a new short-acting neuromuscular blocking agent.

Rapacuronium is a new steroidal, nondepolarizing, neuromuscular blocking agent. It appears to be the least potent of all available nondepolarizing muscle relaxants. Its onset of action resembles that of succinylcholine, and its recovery times are shorter than those of other nondepolarizing agents. The clinical duration of rapacuronium can be shortened significantly with early (2 min) administration of neostigmine, which may be beneficial in patients with difficult airway or failed intubation. Rapacuronium appears to be free of significant cardiovascular complications.

The effects of chronic exercise on anesthesia induced hepatotoxicity.

UNLABELLED: A hypoxic rat model of halothane-induced hepatotoxicity, which is known to produce liver damage, was used to determine the effects of chronic exercise on halothane-induced hepatotoxicity and on reduced hepatic glutathione (GSH) levels. Metabolism of volatile anesthetics may generate metabolites that can cause mild and transient hepatotoxicity. METHODS: Six male Sprague-Dawley rats completed a 10-wk (5 d x wk(-1)) treadmill running protocol. Twelve age-matched animals were used as sedentary controls. After the completion of exercise training, rats were exposed for 2 h to 1% halothane in 14% O2. Twenty-four hours later, animals were anesthetized with sodium pentobarbital and sacrificed. Livers were excised, stained, and evaluated for hepatotoxicity using a histopathological 0 (normal) to 5 (severe damage) point categorical scale and for the determination of GSH levels. RESULTS: Median histopathologic scores revealed significantly lower indications of hepatotoxicity in exercise animals as compared with control animals (score = 0.25 vs 1.50; P < 0.05). Liver damages scores between 1 and 5 were observed in 75% (9 of 12) of the control animals, whereas only 1 of 6 exercise animals had a score greater than 1 (P < 0.05). No significant difference was observed in reduced GSH levels. CONCLUSIONS: Chronic exercise improves the detoxicant ability of the liver for halothane anesthesia as noted by the ameliorated liver damage and reduced incidence of halothane-induced hepatotoxicity in the exercise animals.

Isokinetic peak torque and hamstring/quadriceps ratios in young basketball players. Effects of age, velocity, and contraction mode.

AIM: The purpose of this study was to provide an extensive isokinetic profile, including peak torque and "functional" and "conventional" muscle group ratios, of basketball players throughout the developmental years 12-17. Furthermore, we investigated the effects of age and angular velocity on peak torque and reciprocal muscle group ratios, and observed the force-velocity pattern. METHODS: Basketball players (n=180) 12 to 17 years. were divided according to their age in 6 equal (n=30) groups aged 12, 13, 14, 15, 16, 17 years. All subjects performed maximum knee extension and flexion efforts at 60 inverted exclamation mark /s and 180 inverted exclamation mark /s angular velocities under eccentric and concentric conditions. The absolute (Nm) peak torque was measured, and the relative peak torque (PT/BW) and "functional" and "conventional" reciprocal muscle group ratio (%) were calculated. RESULTS: PT/BW values of knee flexors ranged from 0.98 to 2.29 Nm/kg and of extensors from 1.53 to 3.69 Nm/kg, across all age, velocity, and muscle action levels. PT/BW was higher at slow speed and during eccentric contraction irrespective of age and angular velocity/muscle action. The results indicated a significant (p<0.05) age-related increase in peak torque independent of changes in BW. The force-velocity patterns were similar across ages. The "functional" and "conventional" ratios were not affected by age, but increased with increase in angular velocity, except the CON(KF)/ECC(KE) ratio that was higher (p<0.05) at slow speed. CONCLUSION: The present study provides an extensive isokinetic profile of a knee joint in basketball players throughout developmental years 12-17. Coaches and physical therapist may use these information when evaluating and planning exercise programs during training and rehabilitation.

Reductive stress after exercise: The issue of redox individuality.

Exercise has been consistently used as an oxidant stimulus in redox biology studies. However, previous studies have focused on group differences and did not examine individual differences. As a result, it remains untested whether all individuals experience oxidative stress after acute exercise. Therefore, the main aim of the present study was to investigate whether some individuals exhibit unexpected responses after an acute eccentric (i.e., muscle-damaging) exercise session. Ninety eight (N = 98) young men performed an isokinetic eccentric exercise bout with the knee extensors. Plasma, erythrocytes and urine samples were collected immediately before and 2 days post-exercise. Three commonly used redox biomarkers (F2-isoprostanes, protein carbonyls and glutathione) were assayed. As expected, the two oxidant biomarkers (F2-isoprostanes and protein carbonyls) significantly increased 2 days after exercise (46% and 61%, respectively); whereas a significant decrease in glutathione levels (by -21%) was observed after exercise. A considerable number of the participants exhibited changes in the levels of biomarkers in the opposite, unexpected direction than the group average. More specifically, 13% of the participants exhibited a decrease in F2-isoprostanes and protein carbonyls and 10% of the participants exhibited an increase in glutathione levels. Furthermore, more than 1 out of 3 individuals exhibited either unexpected or negligible (from 0% to ± 5%) responses to exercise in at least one redox biomarker. It was also observed that the initial values of redox biomarkers are important predictors of the responses to exercise. In conclusion, although exercise induces oxidative stress in the majority of individuals, it can induce reductive stress or negligible stress in a considerable number of people. The data presented herein emphasize that the mean response to a redox stimulus can be very misleading. We believe that the wide variability (including the cases of reductive stress) described is not limited to the oxidant stimulus used and the biomarkers selected.

Reduced metaboreflex control of blood pressure during exercise in individuals with intellectual disability: a possible contributor to exercise intolerance.

The aim was to investigate the hemodynamic responses to isometric handgrip exercise (HG) and examine the role of the muscle metaboreflex in the exercise pressor response in individuals with intellectual disability (IID) and non-disabled control subjects. Eleven males with mild-moderate intellectual disabilities and eleven non-disabled males performed a testing protocol involving 3-min periods of baseline, HG exercise (at 30% MVC), circulatory occlusion, and recovery. The same protocol was repeated without occlusion. At baseline, no differences were detected between groups in beat-to-beat mean arterial pressure (MAP), heart rate (HR), stroke volume, and peripheral resistance. IID were able to sustain an exercise MAP response at comparable levels to the control group exerting similar peripheral resistance; however, IID exhibited a blunted chronotropic response to HG and a diminished exercise vagal withdrawal compared to controls. During occlusion, IID exhibited a lower pressor response than their control peers, associated with a lower increase in peripheral resistance during this task. In conclusion, although intellectual disabilities can be the consequence of many different genes, IID share common deficits in the chronotropic response to exercise and a blunted metaboreflex-induced pressor response.

Regression of cellular hypertrophy after left ventricular assist device support.

BACKGROUND: Although multiple studies have shown that the left ventricular assist device (LVAD) improves distorted cardiac geometry, the pathological mechanisms of the "reverse remodeling" of the heart are unknown. Our goal was to determine the effects of LVAD support on cardiac myocyte size and shape. METHODS AND RESULTS: Isolated myocytes were obtained at cardiac transplantation from 30 failing hearts (12 ischemic, 18 nonischemic) without LVAD support, 10 failing hearts that received LVAD support for 75+/-15 days, and 6 nonfailing hearts. Cardiac myocyte volume, length, width, and thickness were determined by use of previously validated techniques. Isolated myocytes from myopathic hearts exhibited increased volume, length, width, and length-to-thickness ratio compared with normal myocytes (P<0.05). However, there were no differences in any parameter between myocytes from ischemic and nonischemic cardiomyopathic hearts. Long-term LVAD support resulted in a 28% reduction in myocyte volume, 20% reduction in cell length, 20% reduction in cell width, and 32% reduction in cell length-to-thickness ratio (P<0.05). In contrast, LVAD support was associated with no change in cell thickness. These cellular changes were associated with reductions in left ventricular dilation and left ventricular mass measured echocardiographically in 6 of 10 LVAD-supported patients. CONCLUSIONS: These studies suggest that the regression of cellular hypertrophy is a major contributor to the "reverse remodeling" of the heart after LVAD implantation. The favorable alterations in geometry that occur in parallel fashion at both the organ and cellular levels may contribute to reduced wall stress and improved mechanical performance after LVAD support.

Serum leptin during recovery following maximal incremental and prolonged exercise.

This study investigated the delayed circulating leptin response to maximal and prolonged treadmill exercise. Six healthy untrained males performed three sessions after an overnight fast: control, maximal exercise, and prolonged exercise at 50% of maximal oxygen consumption. Blood samples were collected prior to exercise, at the end of exercise, and at 60, 120, 180, and 240 min following exercise and control sessions. Blood samples were analyzed for serum leptin, insulin, glucose, free fatty acids, and glycerol. Hemoglobin and hematocrit were measured to correct for plasma volume changes. Resting energy expenditure (REE) and body fat (BF) were also assessed. Immediately at the end of maximal and prolonged exercise, and during the 4 hours of recovery, serum leptin levels did not change significantly compared to their respective baseline values. At 240 min of recovery serum leptin decreased 7% and 9% (p>0.05) from the baseline in the maximal and prolonged sessions, respectively. In the control experiment serum leptin decreased 27% from the baseline at 240 min of the recovery (p < 0.05). No significant differences were found in leptin values between the control and exercise sessions. Control serum leptin was positively correlated (p < 0.05) to BF (r = 0.88) and glucose (r=0.96), and negatively correlated to REE (r= -0.81). In conclusion, maximal or prolonged exercise do not appear to have an influence on circulating serum leptin in the delayed (4 hr) post exercise recovery period.

Dose of compound A, not sevoflurane, determines changes in the biochemical markers of renal injury in healthy volunteers.

UNLABELLED: Administration of sevoflurane in a circle absorption system generates Compound A, a nephrotoxin in rats. Reports examining the potential of Compound A to produce renal injury in humans have provided conflicting results. We tested the possibility that there is a threshold to Compound A-induced renal injury in humans and that, above this threshold, renal injury increases with increasing doses of Compound A. Eleven volunteers received 3% sevoflurane for 8 h at 2 L/min, and three volunteers received 3% sevoflurane for 8 h at 4-6 L/min. We measured inspired and expired concentrations of Compound A and urinary excretion of albumin, alpha-glutathione-S-transferase (GST), and glucose. The median urinary excretion of albumin, glucose, and alpha-GST for the first 3 days after anesthesia increased significantly from preanesthetic values in the 2-L/min group. Compound A doses < 240 ppm-h resulted in normal urinary excretion of albumin, glucose, and alpha-GST. Five of seven subjects who received doses > 240 ppm-h had abnormal excretion of albumin, and six of seven had abnormal alpha-GST urinary excretion (P < 0.05). Urinary excretion of albumin, alpha-GST, and glucose was normal by 14 days after exposure. We conclude that sevoflurane administration for 8 h at 2 L/min results in albuminuria and enzymuria when the dose of Compound A exceeds 240 ppm-h. That is, a Compound A concentration of 30 ppm breathed for > or = 8 h may produce transient renal injury. IMPLICATIONS: We examined the dose-response relationship of sevoflurane/Compound A and urinary excretion of albumin, glucose, and alpha-GST. Sevoflurane exposure for 8 h at a 2-L/min inflow rate produces transient albuminuria and enzymuria in healthy volunteers when the dose of Compound A exceeds 240 ppm-h (30 ppm for 8 h).