Peak muscle perfusion and oxygen uptake in humans: importance of precise estimates of muscle mass.

The knee extensor exercise model was specifically developed to enable in vivo estimates of peak muscle blood flow and O(2) uptake in humans. The original finding, using thermodilution measurements to measure blood flow in relation to muscle mass [P. Andersen and B. Saltin. J. Physiol. (Lond.) 366: 233-249, 1985], was questioned, however, as the measurements were two- to threefold higher than those previously obtained with the (133)Xe clearance and the plethysmography technique. As thermodilution measurements have now been confirmed by other methods and independent research groups, we aimed to address the impact of muscle mass estimates on the peak values of muscle perfusion and O(2) uptake. In the present study, knee extensor volume was determined from multiple measurements with computer tomography along the full length of the muscle. In nine healthy humans, quadriceps muscle volume was 2.36 +/- 0.17 (range 1. 31-3.27) liters, corresponding to 2.48 +/- 0.18 (range 1.37-3.43) kg. Anthropometry overestimated the muscle volume by approximately 21-46%, depending on whether quadriceps muscle length was estimated from the patella to either the pubic bone, inguinal ligament, or spina iliaca anterior superior. One-legged, dynamic knee extensor exercise up to peak effort of 67 +/- 7 (range 55-100) W rendered peak values for leg blood flow (thermodilution) of 5.99 +/- 0.66 (range 4.15-9.52) l/min and leg O(2) uptake of 856 +/- 109 (range 590-1,521) ml/min. Muscle perfusion and O(2) uptake reached peak values of 246 +/- 24 (range 149-373) and 35.2 +/- 3.7 (range 22.6-59. 6) ml. min(-1). 100 g muscle(-1), respectively. These peak values are approximately 19-33% larger than those attained by applying anthropometric muscle mass estimates. In conclusion, the present findings emphasize that peak perfusion and O(2) uptake in human skeletal muscle may be up to approximately 30% higher than previous anthropometric-based estimates that use equivalent techniques for blood flow measurements.     

Hemodynamics and O2 uptake during maximal knee extensor exercise in untrained and trained human quadriceps muscle: effects of hyperoxia.

To elucidate the potential limitations on maximal human quadriceps O2 capacity, six subjects trained (T) one quadriceps on the single-legged knee extensor ergometer (1 h/day at 70% maximum workload for 5 days/wk), while their contralateral quadriceps remained untrained (UT). Following 5 wk of training, subjects underwent incremental knee extensor tests under normoxic (inspired O2 fraction = 21%) and hyperoxic (inspired O2 fraction = 60%) conditions with the T and UT quadriceps. Training increased quadriceps muscle mass (2.9 +/- 0.2 to 3.1 +/- 0.2 kg), but did not change fiber-type composition or capillary density. The T quadriceps performed at a greater peak power output than UT, under both normoxia (101 +/- 10 vs. 80 +/- 7 W; P < 0.05) and hyperoxia (97 +/- 11 vs. 81 +/- 7 W; P < 0.05) without further increases with hyperoxia. Similarly, thigh peak O2 consumption, blood flow, vascular conductance, and O2 delivery were greater in the T vs. the UT thigh (1.4 +/- 0.2 vs. 1.1 +/- 0.1 l/min, 8.4 +/- 0.8 vs. 7.2 +/- 0.8 l/min, 42 +/- 6 vs. 35 +/- 4 ml x min(-1) x mmHg(-1), 1.71 +/- 0.18 vs. 1.51 +/- 0.15 l/min, respectively) but were not enhanced with hyperoxia. Oxygen extraction was elevated in the T vs. the UT thigh, whereas arteriovenous O2 difference tended to be higher (78 +/- 2 vs. 72 +/- 4%, P < 0.05; 160 +/- 8 vs. 154 +/- 11 ml/l, respectively; P = 0.098) but again were unaltered with hyperoxia. In conclusion, the present results demonstrate that the increase in quadriceps muscle O2 uptake with training is largely associated with increases in blood flow and O2 delivery, with smaller contribution from increases in O2 extraction. Furthermore, the elevation in peak muscle blood flow and vascular conductance with endurance training seems to be related to an enhanced vasodilatory capacity of the vasculature perfusing the quadriceps muscle that is unaltered by moderate hyperoxia.     

Glutamate availability is important in intramuscular amino acid metabolism and TCA cycle intermediates but does not affect peak oxidative metabolism.

Muscle glutamate is central to reactions producing 2-oxoglutarate, a tricarboxylic acid (TCA) cycle intermediate that essentially expands the TCA cycle intermediate pool during exercise. Paradoxically, muscle glutamate drops approximately 40-80% with the onset of exercise and 2-oxoglutarate declines in early exercise. To investigate the physiological relationship between glutamate, oxidative metabolism, and TCA cycle intermediates (i.e., fumarate, malate, 2-oxoglutarate), healthy subjects trained (T) the quadriceps of one thigh on the single-legged knee extensor ergometer (1 h/day at 70% maximum workload for 5 days/wk), while their contralateral quadriceps remained untrained (UT). After 5 wk of training, peak oxygen consumption (VO2peak) in the T thigh was greater than that in the UT thigh (P<0.05); VO2peak was not different between the T and UT thighs with glutamate infusion. Peak exercise under control conditions revealed a greater glutamate uptake in the T thigh compared with rest (7.3+/-3.7 vs. 1.0+/-0.1 micromol.min(-1).kg wet wt(-1), P<0.05) without increase in TCA cycle intermediates. In the UT thigh, peak exercise (vs. rest) induced an increase in fumarate (0.33+/-0.07 vs. 0.02+/-0.01 mmol/kg dry wt (dw), P<0.05) and malate (2.2+/-0.4 vs. 0.5+/-0.03 mmol/kg dw, P<0.05) and a decrease in 2-oxoglutarate (12.2+/-1.6 vs. 32.4+/-6.8 micromol/kg dw, P<0.05). Overall, glutamate infusion increased arterial glutamate (P<0.05) and maintained this increase. Glutamate infusion coincided with elevated fumarate and malate (P<0.05) and decreased 2-oxoglutarate (P<0.05) at peak exercise relative to rest in the T thigh; there were no further changes in the UT thigh. Although glutamate may have a role in the expansion of the TCA cycle, glutamate and TCA cycle intermediates do not directly affect VO2peak in either trained or untrained muscle.     

Effect of exercise-induced arterial hypoxemia on quadriceps muscle fatigue in healthy humans

The effect of exercise-induced arterial hypoxemia (EIAH) on quadriceps muscle fatigue was assessed in 11 male endurance-trained subjects [peak O2 uptake (VO2 peak) = 56.4 +/- 2.8 ml x kg(-1) x min(-1); mean +/- SE]. Subjects exercised on a cycle ergometer at >or=90% VO2 peak) to exhaustion (13.2 +/- 0.8 min), during which time arterial O2 saturation (Sa(O2)) fell from 97.7 +/- 0.1% at rest to 91.9 +/- 0.9% (range 84-94%) at end exercise, primarily because of changes in blood pH (7.183 +/- 0.017) and body temperature (38.9 +/- 0.2 degrees C). On a separate occasion, subjects repeated the exercise, for the same duration and at the same power output as before, but breathed gas mixtures [inspired O2 fraction (Fi(O2)) = 0.25-0.31] that prevented EIAH (Sa(O2) = 97-99%). Quadriceps muscle fatigue was assessed via supramaximal paired magnetic stimuli of the femoral nerve (1-100 Hz). Immediately after exercise at Fi(O2) 0.21, the mean force response across 1-100 Hz decreased 33 +/- 5% compared with only 15 +/- 5% when EIAH was prevented (P < 0.05). In a subgroup of four less fit subjects, who showed minimal EIAH at Fi(O2) 0.21 (Sa(O2) = 95.3 +/- 0.7%), the decrease in evoked force was exacerbated by 35% (P < 0.05) in response to further desaturation induced via Fi(O2) 0.17 (Sa(O2) = 87.8 +/- 0.5%) for the same duration and intensity of exercise. We conclude that the arterial O2 desaturation that occurs in fit subjects during high-intensity exercise in normoxia (-6 +/- 1% DeltaSa(O2) from rest) contributes significantly toward quadriceps muscle fatigue via a peripheral mechanism.     

Gradual increase in leg oxygen uptake during repeated submaximal contractions in humans

We examine whether muscle oxygen consumption (VO2) increases gradually during repeated submaximal isometric contractions. Six subjects made two-legged isometric quadriceps contractions at 30% maximal voluntary contraction for 6 s with 4 s of rest between until exhaustion (58 +/- 8 min). Blood samples were taken from the femoral vein and artery, and blood velocity was recorded by ultrasound-Doppler technique in the femoral artery. Blood flow was calculated from velocity and artery diameter values. Leg VO2 increased sixfold within the 1st min of exercise. A further doubling of the VO2 was seen during the remainder of the exercise, reaching 307 +/- 22 ml/min at exhaustion. This latter increase was due to a 54% increase in blood flow and a 34% increase in oxygen extraction. After 20 min of recovery VO2 was still 75% higher than preexercise values. The results show a twofold increase in energy demand of the working muscle during repeated constant-force isometric contractions. The increased energy cost of contraction is probably localized at the cellular level, and it parallels fatigue determined as decreased force-generating capacity.     

Muscle oxygen kinetics at onset of intense dynamic exercise in humans

The present study examined the onset and the rate of rise of muscle oxidation during intense exercise in humans and whether oxygen availability limits muscle oxygen uptake in the initial phase of intense exercise. Six subjects performed 3 min of intense one-legged knee-extensor exercise [65.3 +/- 3.7 (means +/- SE) W]. The femoral arteriovenous blood mean transit time (MTT) and time from femoral artery to muscle microcirculation was determined to allow for an examination of the oxygen uptake at capillary level. MTT was 15.3 +/- 1.8 s immediately before exercise, 10.4 +/- 0.7 s after 6 s of exercise, and 4.7 +/- 0.5 s at the end of exercise. Arterial venous O(2) difference (a-v(diff) O(2)) of 18 +/- 5 ml/l before the exercise was unchanged after 2 s, but it increased (P < 0.05) after 6 s of exercise to 43 +/- 10 ml/l and reached 146 +/- 4 ml/l at the end of exercise. Thigh oxygen uptake increased (P < 0.05) from 32 +/- 8 to 102 +/- 28 ml/min after 6 s of exercise and to 789 +/- 88 ml/min at the end of exercise. The time to reach half-peak a-v(diff) O(2) and thigh oxygen uptake was 13 +/- 2 and 25 +/- 3 s, respectively. The difference between thigh oxygen delivery (blood flow x arterial oxygen content) and thigh oxygen uptake increased (P < 0.05) after 6 s and returned to preexercise level after 14 s. The present data suggest that, at the onset of exercise, oxygen uptake of the exercising muscles increases after a delay of only a few seconds, and oxygen extraction peaks after approximately 50 s of exercise. The limited oxygen utilization in the initial phase of intense exercise is not caused by insufficient oxygen availability.     

Vascular and metabolic response to isolated small muscle mass exercise: effect of age

To determine the effect of age on quadriceps muscle blood flow (QMBF), leg vascular resistance (LVR), and maximum oxygen uptake (QVO2 max), a thermal dilution technique was used in conjunction with arterial and venous femoral blood sampling in six sedentary young (19.8 +/- 1.3 yr) and six sedentary old (66.5 +/- 2.1 yr) males during incremental knee extensor exercise (KE). Young and old attained a similar maximal KE work rate (WRmax) (young: 25.2 +/- 2.1 and old: 24.1 +/- 4 W) and QVO2 max (young: 0.52 +/- 0.03 and old: 0.42 +/- 0.05 l/min). QMBF during KE was lower in old subjects by approximately 500 ml/min across all work rates, with old subjects demonstrating a significantly lower QMBF/W (old: 174 +/- 20 and young: 239 +/- 46 ml. min-1. W-1). Although the vasodilatory response to incremental KE was approximately 142% greater in the old (young: 0.0019 and old: 0.0046 mmHg. min. ml-1. W-1), consistently elevated leg vascular resistance (LVR) in the old, approximately 80% higher LVR in the old at 50% WR and approximately 40% higher LVR in the old at WRmax (young: 44.1 +/- 3.6 and old: 31.0 +/- 1.7 mmHg. min. ml-1), dictated that during incremental KE the LVR of the old subjects was never less than that of the young subjects. Pulse pressures, indicative of arterial vessel compliance, were approximately 36% higher in the old subjects across all work rates. In conclusion, well-matched sedentary young and old subjects with similar quadriceps muscle mass achieved a similar WRmax and QVO2 max during incremental KE. The old subjects, despite a reduced QMBF, had a greater vasodilatory response to incremental KE. Given that small muscle mass exercise, such as KE, utilizes only a fraction of maximal cardiac output, peripheral mechanisms such as consistently elevated leg vascular resistance and greater pulse pressures appear to be responsible for reduced blood flow persisting throughout graded KE in the old subjects.     

Glucose ingestion blunts hormone-sensitive lipase activity in contracting human skeletal muscle

To examine the effect of attenuated epinephrine and elevated insulin on intramuscular hormone sensitivity lipase activity (HSLa) during exercise, seven men performed 120 min of semirecumbent cycling (60% peak pulmonary oxygen uptake) on two occasions while ingesting either 250 ml of a 6.4% carbohydrate (GLU) or sweet placebo (CON) beverage at the onset of, and at 15 min intervals throughout, exercise. Muscle biopsies obtained before and immediately after exercise were analyzed for HSLa. Blood samples were simultaneously obtained from a brachial artery and a femoral vein before and during exercise, and leg blood flow was measured by thermodilution in the femoral vein. Net leg glycerol and lactate release and net leg glucose and free fatty acid (FFA) uptake were calculated from these measures. Insulin and epinephrine were also measured in arterial blood before and throughout exercise. During GLU, insulin was elevated (120 min: CON, 11.4 +/- 2.4, GLU, 35.3 +/- 6.9 pM, P < 0.05) and epinephrine suppressed (120 min: CON, 6.1 +/- 2.5, GLU, 2.1 +/- 0.9 nM; P < 0.05) compared with CON. Carbohydrate feeding also resulted in suppressed (P < 0.05) HSLa relative to CON (120 min: CON, 1.71 +/- 0.18, GLU, 1.27 +/- 0.16 mmol.min-1.kg dry mass-1). There were no differences in leg lactate or glycerol release when trials were compared, but leg FFA uptake was lower (120 min: CON, 0.29 +/- 0.06, GLU, 0.82 +/- 0.09 mmol/min) and leg glucose uptake higher (120 min: CON, 3.16 +/- 0.59, GLU, 1.37 +/- 0.37 mmol/min) in GLU compared with CON. These results demonstrate that circulating insulin and epinephrine play a role in HSLa in contracting skeletal muscle.     

Effect of lowered muscle temperature on the physiological response to exercise in men

The effect of low muscle temperature on the response to dynamic exercise was studied in six healthy men who performed 42 min of exercise on a cycle ergometer at an intensity of 70% of their maximal O2 uptake. Experiments were performed under control conditions, i.e. from rest at room temperature, and following 45 min standing with legs immersed in a water bath at 12 degrees C. The water bath reduced quadriceps muscle temperature (at 3 cm depth) from 36.4 (SD 0.5) degrees C to 30.5 (SD 1.7) degrees C. Following cooling, exercise heart rate was initially lower, the mean difference ranged from 13 (SD 4) beats.min-1 after 6 min of exercise, to 4 (SD 2) beats.min-1 after 24 min of exercise. Steady-state oxygen uptake was consistently higher (0.2 l.min-1). However, no difference could be discerned in the kinetics of oxygen uptake at the onset of exercise. During exercise after cooling a significantly higher peak value was found for the blood lactate concentration compared to that under control conditions. The peak values were both reached after approximately 9 min of exercise. After 42 min of exercise the blood lactate concentrations did not differ significantly, indicating a faster rate of removal during exercise after cooling. We interpreted these observations as reflecting a relatively higher level of muscle hypoxia at the onset of exercise as a consequence of a cold-induced vasoconstriction. The elevated steady-state oxygen uptake may in part have been accounted for by the energetic costs of removal of the extra lactate released into the blood consequent upon initial tissue hypoxia.     

Sex differences in leg vasodilation during graded knee extensor exercise in young adults.

Limb vascular conductance responses to pharmacological and nonexercise vasodilator stimuli are generally augmented in women compared with men. In the present investigation, we tested the hypothesis that exercise-induced vasodilator responses are also greater in women than men. Sixteen women and 15 men (20-30 yr) with similar fitness and activity levels performed graded quadriceps exercise (supine, single-leg knee extensions, 40 contractions/min) to maximal exertion. Active limb hemodynamics (left common femoral artery diameter and volumetric blood flow), heart rate (ECG), and beat-to-beat mean arterial blood pressure (MAP; radial artery tonometry) were measured during each 3-min workload (4.8 and 8 W/stage for women and men, respectively). The hyperemic response to exercise (slope of femoral blood flow vs. workload) was greater (P < 0.01) in women as was femoral blood flow at workloads >15 W. The leg vasodilatory response to exercise (slope of calculated femoral vascular conductance vs. absolute workload) was also greater in women than in men (P < 0.01) because of the sex difference in hyperemia and the women's lower MAP ( approximately 10-15 mmHg) at all workloads (P < 0.05). The femoral artery dilated to a significantly greater extent in the women ( approximately 0.5 mm) than in the men ( approximately 0.1 mm) across all submaximal workloads. At maximal exertion, femoral vascular conductance was lower in the men (men, 18.0 +/- 0.6 ml.min(-1)xmmHg(-1); women, 22.6 +/- 1.4 mlxmin(-1)xmmHg(-1); P < 0.01). Collectively, these findings suggest that the vasodilatory response to dynamic leg exercise is greater in young women vs. men.     

Effect of contraction frequency on leg blood flow during knee extension exercise in humans.

Previous studies in isolated muscle preparations have shown that muscle blood flow becomes compromised at higher contraction frequencies. The purpose of this study was to examine the effect of increases in contraction frequency and muscle tension on mean blood flow (MBF) during voluntary exercise in humans. Nine male subjects [23.6 +/- 3.7 (SD) yr] performed incremental knee extension exercise to exhaustion in the supine position at three contraction frequencies [40, 60, and 80 contractions/min (cpm)]. Mean blood velocity of the femoral artery was determined beat by beat using Doppler ultrasound. MBF was calculated by using the diameter of the femoral artery determined at rest using echo Doppler ultrasound. The work rate (WR) achieved at exhaustion was decreased (P < 0.05) as contraction frequency increased (40 cpm, 16.2 +/- 1.4 W; 60 cpm, 14.8 +/- 1.4 W; 80 cpm, 13.2 +/- 1.3 W). MBF was similar across the contraction frequencies at rest and during the first WR stage but was higher (P < 0.05) at 40 than 80 cpm at exercise intensities >5 W. MBF was similar among contraction frequencies at exhaustion. In humans performing knee extension exercise in the supine position, muscle contraction frequency and/or muscle tension development may appreciably affect both the MBF and the amplitude of the contraction-to-contraction oscillations in muscle blood flow.     

Enhanced leg exercise endurance with a high-carbohydrate diet and dihydroxyacetone and pyruvate

The effects of dietary supplementation of dihydroxyacetone and pyruvate (DHAP) on metabolic responses and endurance capacity during leg exercise were determined in eight untrained males (20-30 yr). During the 7 days before exercise, a high-carbohydrate diet was consumed (70% carbohydrate, 18% protein, 12% fat; 35 kcal/kg body weight). One hundred grams of either Polycose (placebo) or dihydroxyacetone and pyruvate (treatment, 3:1) were substituted for a portion of carbohydrate. Dietary conditions were randomized, and subjects consumed each diet separated by 7-14 days. After each diet, cycle ergometer exercise (70% of peak oxygen consumption) was performed to exhaustion. Biopsy of the vastus lateralis muscle was obtained before and after exercise. Blood samples were drawn through radial artery and femoral vein catheters at rest, after 30 min of exercise, and at exercise termination. Leg endurance was 66 +/- 4 and 79 +/- 2 min after placebo and DHAP, respectively (P less than 0.01). Muscle glycogen at rest and exhaustion did not differ between diets. Whole leg arteriovenous glucose difference was greater (P less than 0.05) for DHAP than for placebo at rest (0.36 +/- 0.05 vs. 0.19 +/- 0.07 mM) and after 30 min of exercise (1.06 +/- 0.14 vs. 0.65 +/- 0.10 mM) but did not differ at exhaustion. Plasma free fatty acids, glycerol, and beta-hydroxybutyrate were similar during rest and exercise for both diets. Estimated total glucose oxidation during exercise was 165 +/- 17 and 203 +/- 15 g after placebo and DHAP, respectively (P less than 0.05). It is concluded that feeding of DHAP for 7 days in conjunction with a high carbohydrate diet enhances leg exercise endurance capacity by increasing glucose extraction by muscle.     

Hyperthermia and central fatigue during prolonged exercise in humans.

The present study investigated the effects of hyperthermia on the contributions of central and peripheral factors to the development of neuromuscular fatigue. Fourteen men exercised at 60% maximal oxygen consumption on a cycle ergometer in hot (40 degrees C; hyperthermia) and thermoneutral (18 degrees C; control) environments. In hyperthermia, the core temperature increased throughout the exercise period and reached a peak value of 40.0 +/- 0.1 degrees C (mean +/- SE) at exhaustion after 50 +/- 3 min of exercise. In control, core temperature stabilized at approximately 38.0 +/- 0.1 degrees C, and exercise was maintained for 1 h without exhausting the subjects. Immediately after the cycle trials, subjects performed 2 min of sustained maximal voluntary contraction (MVC) either with the exercised legs (knee extension) or with a "nonexercised" muscle group (handgrip). The degree of voluntary activation during sustained maximal knee extensions was assessed by superimposing electrical stimulation (EL) to nervus femoralis. Voluntary knee extensor force was similar during the first 5 s of contraction in hyperthermia and control. Thereafter, force declined in both trials, but the reduction in maximal voluntary force was more pronounced in the hyperthermic trial, and, from 30 to 120 s, the force was significantly lower in hyperthermia compared with control. Calculation of the voluntary activation percentage (MVC/MVC + EL) revealed that the degree of central activation was significantly lower in hyperthermia (54 +/- 7%) compared with control (82 +/- 6%). In contrast, total force of the knee extensors (MVC + force from EL) was not different in the two trials. Force development during handgrip contraction followed the same pattern of response as was observed for the knee extensors. In conclusion, these data demonstrate that the ability to generate force during a prolonged MVC is attenuated with hyperthermia, and the impaired performance is associated with a reduction in the voluntary activation percentage.     

Effects of exercise on GLUT-4 and glycogenin gene expression in human skeletal muscle.

To investigate the effect of exercise on GLUT-4, hexokinase, and glycogenin gene expression in human skeletal muscle, 10 untrained subjects (6 women and 4 men, 21.4 +/- 1.2 yr, 66.3 +/- 5.0 kg, peak oxygen consumption = 2.30 +/- 0.19 l/min) exercised for 60 min on a cycle ergometer at a power output requiring 73 +/- 4% peak oxygen consumption. Muscle samples were obtained by needle biopsy before, immediately after, and 3 h after exercise. Gene expression was quantified, relative to 29S ribosomal protein cDNA, by RT-PCR. GLUT-4 gene expression was increased immediately after exercise (1.7 +/- 0.4 vs. 0.9 +/- 0.3 arbitrary units; P < 0.05) and remained significantly higher than baseline 3 h after the end of exercise (2. 2 +/- 0.4 vs. 0.9 +/- 0.3 arbitrary units; P < 0.05). Hexokinase II gene expression was significantly higher than the resting value 3 h after the end of exercise (2.9 +/- 0.4 vs. 1.3 +/- 0.3 arbitrary units; P < 0.05). Exercise increased glycogenin mRNA more than twofold (2.8 +/- 0.6 vs. 1.2 +/- 0.2 arbitrary units; P < 0.05) 3 h after the end of exercise. For the first time, we report that a single bout of exercise is sufficient to cause upregulation of GLUT-4 and glycogenin gene expression in human skeletal muscle. Whether these increases, together with the associated increase in hexokinase II gene expression, lead to increased expression of these key proteins in skeletal muscle and contribute to the enhanced skeletal muscle glucose uptake, glycogen synthesis, and insulin action observed following exercise remains to be determined.     

Exercise hyperventilation, dyspnea sensation, and ergoreflex activation in lone atrial fibrillation

Lone atrial fibrillation may be associated with daily life disability and exercise limitation. The extracardiac pathophysiology of these effects is poorly explored. In 35 subjects with lone atrial fibrillation (mean age 67 +/- 7 yr), we investigated pulmonary function, symptom-limited cardiopulmonary exercise performance, muscle ergoreflex (handgrip exercise) contribution to ventilation, and brachial artery flow-mediated dilation (as a measure of endothelial function) before and after (average interval 20 +/- 5 days) restoring sinus rhythm with external cardioversion. Respiratory volumes and lung diffusing capacity at rest were within normal limits during both atrial fibrillation and after restoring sinus rhythm. Cardioversion was associated with the following changes: a decrease of the slope of exercise ventilation vs. CO2 production (from 35 +/- 5 to 29 +/- 3; P <0.01) and of dyspnea sensation (Borg score from 4 to 2) and an increase of peak oxygen uptake (Vo2; from 16 +/- 4 to 20 +/- 5 ml.min(-1).kg(-1); P <0.01), Vo2 at anaerobic threshold (from 11 +/- 2 to 13 +/- 2 ml.min(-1).kg(-1); P <0.05), and O2 pulse (from 8 +/- 3 to 11 +/- 3 ml/beat; P <0.01). After cardioversion, the observed improvement in ventilatory efficiency was accompanied by a significant peak end-tidal CO2 increase (from 33 +/- 2 to 37 +/- 2 mmHg; P <0.01) and no changes in dead space-to-tidal volume ratio (from 0.23 +/- 0.03 to 0.23 +/- 0.02; P=not significant). In addition, the ergoreflex contribution to ventilation was remarkably attenuated, and the brachial artery flow-mediated dilatation was significantly augmented (from 0.32 +/- 0.07 to 0.42 +/- 0.08 mm; P <0.01). Ten patients had atrial fibrillation relapse and, compared with values after restoration of regular sinus rhythm, invariably showed worsening of endothelial function, exercise ventilatory efficiency, and muscle ergoreflex contribution to ventilation. In subjects with lone atrial fibrillation, an impairment in ventilatory efficiency appears to be involved in the pathophysiology of exercise limitation, and to be primarily related with a demodulated peripheral control of ventilation.     

Low-intensity training produces muscle adaptations in rats with femoral artery stenosis.

The effectiveness of a mild-intensity exercise program to induce adaptations within skeletal muscle of animals with peripheral arterial insufficiency was evaluated using an isolated perfused hindlimb preparation at a muscle blood flow similar to the peak found in vivo. Adult rats were subjected to bilateral femoral artery stenosis sufficient to limit peak blood flow during exercise but not alter resting blood flow. Stenosed-trained (Sten-Trained) rats walked on a treadmill at an easily achieved speed (20 m/min with a 15% grade) 5 days wk. Exercise tolerance improved from 10 min initially to 2 h/day. Non-stenosed-sedentary (Non-Sten-Sed) and stenosed-sedentary (Sten-Sed) animals were limited to cage activity. Oxygen delivery to the contracting muscles was similar among groups (7.0 +/- 0.4, 7.3 +/- 0.6, and 6.6 +/- 0.6 mumol.min-1.g-1 in Non-Sten-Sed, Sten-Sed, and Sten-Trained, respectively; n = 13 each). Force development was better maintained by Sten-Trained muscle (P less than 0.001) during a sequence of tetanic contraction conditions. Peak oxygen consumption was greater (P less than 0.05) in the Sten-Trained (5.23 +/- 0.34 mumol.min-1.g-1) than in Non-Sten-Sed (4.08 +/- 0.35) and Sten-Sed (4.34 +/- 0.37) rats. The increased peak oxygen extraction (P less than 0.05) by the muscle of the Sten-Trained rats (82.5 +/- 7.1% of oxygen inflow vs. 58.7 +/- 4.7 and 57.4 +/- 5.0%, respectively) was probably related to the increased muscle capillarity and mitochondrial enzyme activity.(ABSTRACT TRUNCATED AT 250 WORDS)     

Near-maximal fractional oxygen extraction by active skeletal muscle in patients with chronic heart failure.

Systemic oxygen uptake and deep femoral vein oxygen content were determined at peak exercise in 53 patients with chronic heart failure with impaired systolic function (mean left ventricular ejection fraction 0.18; n = 41) or preserved systolic function (mean left ventricular ejection fraction 0.70; n = 12) and in 6 age-matched sedentary normal subjects. At peak exercise, deep femoral vein oxygen content in heart failure patients with impaired systolic function and preserved systolic function were similar, both significantly lower than that of normal subjects (2.5 +/- 0.1, 2.9 +/- 0.2, and 5.0 +/- 0.1 ml/100 ml, respectively; P < 0.05). Deep femoral venous oxygen content was lower in patients with the greater impairment of aerobic capacity, regardless of the underlying systolic function (r = 0.72, P < 0.01). Fractional oxygen extraction in the skeletal muscle at peak exercise is enhanced in patients with chronic heart failure when compared with normal subjects, in proportion to the degree of aerobic impairment.     

Work capacity during 30 days of bed rest with isotonic and isokinetic exercise training

The purpose was to test the hypothesis that twice daily, short-term, variable intensity isotonic and intermittent high-intensity isokinetic leg exercise would maintain peak O2 uptake (VO2) and muscular strength and endurance, respectively, at or near ambulatory control levels during 30 days of -6 degrees head-down bed rest (BR) deconditioning. Nineteen men (aged 32-42 yr) were divided into no exercise control (peak VO2 once/wk, n = 5), isokinetic (Lido ergometer, n = 7), and isotonic (Quinton ergometer, n = 7) groups. Exercise training was conducted in the supine position for two 30-min periods/day for 5 days/wk. Isotonic training was at 60-90% of peak VO2, and isokinetic training (knee flexion-extension) was at 100 degrees/s. Mean (+/- SE) changes (P less than 0.05) in peak VO2 (ml.m-1.kg-1) from ambulatory control to BR day 28 were 44 +/- 4 to 36 +/- 3, -18.2% (3.27-2.60 l/m) for no exercise, 39 +/- 4 to 40 +/- 3, +2.6% (3.13-3.14 l/min) for isotonic, and 44 +/- 3 to 40 +/- 2, -9.1% (3.24-2.90 l/min) for isokinetic. There were no significant changes in any groups in leg peak torque (right knee flexion or extension), leg mean total work, arm total peak torque, or arm mean total work. Mean energy costs for the isotonic and isokinetic exercise training were 446 kcal/h (18.8 +/- 1.6 ml.min-1.kg-1) and 214 kcal/h (8.9 +/- 0.5 ml.m-1.kg-1), respectively. Thus near-peak, variable intensity, isotonic leg exercise maintains peak VO2 during 30 days of BR, while this peak, intermittent, isokinetic leg exercise protocol does not.     

Aerobic metabolism of human quadriceps muscle: in vivo data parallel measurements on isolated mitochondria

The aim of the present study was to examine whether parameters of isolated mitochondria could account for the in vivo maximum oxygen uptake (VO2max) of human skeletal muscle. VO2max and work performance of the quadriceps muscle of six volunteers were measured in the knee extensor model (range 10-18 mmol O2 x min(-1) x kg(-1) at work rates of 22-32 W/kg). Mitochondria were isolated from the same muscle at rest. Strong correlations were obtained between VO2max and a number of mitochondrial parameters (mitochondrial protein, cytochrome aa3, citrate synthase, and respiratory activities). The activities of citrate synthase, succinate dehydrogenase, and pyruvate dehydrogenase, measured in isolated mitochondria, corresponded to, respectively, 15, 3, and 1.1 times the rates calculated from VO2max. The respiratory chain activity also appeared sufficient. Fully coupled in vitro respiration, which is limited by the rate of ATP synthesis, could account for, at most, 60% of the VO2max. This might be due to systematic errors or to loose coupling of the mitochondrial respiration under intense exercise.     

Substantial working muscle glycerol turnover during two-legged cycle ergometry

We combined tracer and arteriovenous (a-v) balance techniques to evaluate the effects of exercise and endurance training on leg triacylglyceride turnover as assessed by glycerol exchange. Measurements on an exercising leg were taken to be a surrogate for working skeletal muscle. Eight men completed 9 wk of endurance training [5 days/wk, 1 h/day, 75% peak oxygen consumption (Vo(2peak))], with leg glycerol turnover determined during two pretraining trials [45 and 65% Vo(2peak) (45% Pre and 65% Pre, respectively)] and two posttraining trials [65% of pretraining Vo(2peak) (ABT) and 65% of posttraining Vo(2peak) (RLT)] using [(2)H(5)]glycerol infusion, femoral a-v sampling, and measurement of leg blood flow. Endurance training increased Vo(2peak) by 15% (45.2 +/- 1.2 to 52.0 +/- 1.8 mlxkg(-1)xmin(-1), P < 0.05). At rest, there was tracer-measured leg glycerol uptake (41 +/- 8 and 52 +/- 15 micromol/min for pre- and posttraining, respectively) even in the presence of small, but significant, net leg glycerol release (-68 +/- 19 and -50 +/- 13 micromol/min, respectively; P < 0.05 vs. zero). Furthermore, while there was no significant net leg glycerol exchange during any of the exercise bouts, there was substantial tracer-measured leg glycerol turnover during exercise (i.e., simultaneous leg muscle uptake and leg release) (uptake, release: 45% Pre, 194 +/- 41, 214 +/- 33; 65% Pre, 217 +/- 79, 201 +/- 84; ABT, 275 +/- 76, 312 +/- 87; RLT, 282 +/- 83, 424 +/- 75 micromol/min; all P < 0.05 vs. corresponding rest). Leg glycerol turnover was unaffected by exercise intensity or endurance training. In summary, simultaneous leg glycerol uptake and release (indicative of leg triacylglyceride turnover) occurs despite small or negligible net leg glycerol exchange, and furthermore, leg glycerol turnover can be substantially augmented during exercise.