Pulmonary VO2 dynamics during treadmill and arm exercise in peripheral arterial disease.

Slowed pulmonary O(2) uptake (Vo(2)) kinetics in peripheral arterial disease (PAD) have been attributed to impaired limb blood flow and/or peripheral muscle metabolic abnormalities. Although PAD results from atherosclerotic occlusive disease in the arteries to the lower extremities, systemic abnormalities affecting whole body O(2) delivery or vascular function in PAD could also partially explain the exercise impairment. To date, the effects of these systemic abnormalities have not been evaluated. To test the hypothesis that the slowed pulmonary Vo(2) kinetics in PAD reflects local and not systemic abnormalities, Vo(2) kinetics were evaluated after the onset of constant-load exercise of the upper and lower limbs in PAD patients and healthy controls (Con). Ten PAD patients and 10 Con without significant cardiopulmonary dysfunction performed multiple transitions from rest to moderate-intensity arm ergometry and treadmill exercise to assess their Vo(2) kinetic responses. Reactive hyperemic (RH) blood flow was assessed in the arms and legs as a measure of endothelial function. Compared with Con, PAD Vo(2) kinetic phase 2 time constants were prolonged during treadmill exercise (PAD 34.3 +/- 9.2 s vs. Con 19.6 +/- 3.5 s; P < 0.01) but not arm exercise (PAD 38.5 +/- 7.5 s vs. Con 32.5 +/- 9.0 s; P > 0.05). RH blood flow was significantly reduced in the legs (PAD 20.7 +/- 8.3 vs. Con 46.1 +/- 17.1 ml.100 ml(-1).min(-1); P < 0.01) and arms of PAD subjects (PAD 34.0 +/- 8.6 vs. Con 50.8 +/- 12.2 ml.100 ml(-1).min(-1); P < 0.01) compared with Con, but RH limb flow was not correlated with arm or treadmill Vo(2) kinetic responses in either group. In summary, slowed pulmonary Vo(2) kinetics in PAD patients occur only with exercise of the lower limbs affected by the arterial occlusive disease process and are not slowed with exercise of the unaffected upper extremities compared with controls. Furthermore, the slowed pulmonary Vo(2) kinetics of the lower extremity could not be explained by any abnormalities in resting cardiac or pulmonary function and were not related to the magnitude of reduction in limb vascular reactivity.     

Ventilatory and gas exchange kinetics during exercise in chronic airways obstruction

The influence of chronic obstructive pulmonary disease (COPD) on exercise ventilatory and gas exchange kinetics was assessed in nine patients with stable airway obstruction (forced expired volume at 1 s = 1.1 +/- 0.33 liters) and compared with that in six normal men. Minute ventilation (VE), CO2 output (VCO2), and O2 uptake (VO2) were determined breath-by-breath at rest and after the onset of constant-load subanaerobic threshold exercise. The initial increase in VE, VCO2, and VO2 from rest (phase I), the subsequent slow exponential rise (phase II), and the steady-state (phase III) responses were analyzed. The COPD group had a significantly smaller phase I increase in VE (3.4 +/- 0.89 vs. 6.8 +/- 1.05 liters/min), VCO2 (0.10 +/- 0.03 vs. 0.22 +/- 0.03 liters/min), VO2 (0.10 +/- 0.03 vs. 0.24 +/- 0.04 liters/min), heart rate (HR) (6 +/- 0.9 vs. 16 +/- 1.4 beats/min), and O2 pulse (0.93 +/- 0.21 vs. 2.2 +/- 0.45 ml/beat) than the controls. Phase I increase in VE was significantly correlated with phase I increase in VO2 (r = 0.88) and HR (r = 0.78) in the COPD group. Most patients also had markedly slower phase II kinetics, i.e., longer time constants (tau) for VE (87 +/- 7 vs. 65 +/- 2 s), VCO2 (79 +/- 6 vs. 63 +/- 3 s), and VO2 (56 +/- 5 vs. 39 +/- 2 s) and longer half times for HR (68 +/- 9 vs. 32 +/- 2 s) and O2 pulse (42 +/- 3 vs. 31 +/- 2 s) compared with controls. However, tau VO2/tau VE and tau VCO2/tau VE were similar in both groups. The significant correlations of the phase I VE increase with HR and VO2 are consistent with the concept that the immediate exercise hyperpnea has a cardiodynamic basis. The slow ventilatory kinetics during phase II in the COPD group appeared to be more closely related to a slowed cardiovascular response rather than to any index of respiratory function. O2 breathing did not affect the phase I increase in VE but did slow phase II kinetics in most subjects. This confirms that the role attributed to the carotid bodies in ventilatory control during exercise in normal subjects also operates in patients with COPD.     

Fitness as a determinant of oxygen uptake response to constant-load exercise

Exercise performed above the lactate threshold (OLa) produces a slowly-developing phase of oxygen uptake (VO2) kinetics which elevates VO2 above that predicted from the sub-OLa VO2-work rate relationship. This phenomenon has only been demonstrated, to date, in subjects who were relatively homogeneous with respect to fitness. This investigation therefore examined whether this behaviour occurred at a given absolute VO2 or whether it was a characteristic of supra-OLa exercise in a group of subjects with over a threefold range of OLa (990-3000 ml O2.min-1) and peak VO2 (1600-5260 ml O2.min-1). Twelve healthy subjects performed: 1) exhausting incremental cycle ergometer exercise for estimation of OLa (OLa) and peak VO2, and 11) a series of constant-load tests above and below OLa for determination of the VO2 profile and efficiency of work. During all tests expired ventilation, VO2 and carbon dioxide production were monitored breath-by-breath. The efficiency of work determined during incremental exercise (28.1 +/- 0.7%, means +/- SE, n = 12) did not differ from that determined during sub-OLa constant-load exercise (27.4 +/- 0.5%, p greater than 0.05). For constant-load exercise, VO2 rose above that predicted, from the sub-OLa VO2-work rate relationship, for all supra-OLa work rates. This was evident above 990 ml O2.min-1 in the least fit subject but only above 3000 ml O2.min-1 in the fittest subject. As a consequence the efficiency of work was reduced from 27.4 +/- 0.5% for sub-OLa exercise to 22.6 +/- 0.4% (p less than 0.05) at the lowest supra-OLa work rate (i.e. OLa + 20 W, on average).(ABSTRACT TRUNCATED AT 250 WORDS)     

Oxygen uptake kinetics for moderate exercise are speeded in older humans by prior heavy exercise.

This study examined the effect of heavy-intensity warm-up exercise on O(2) uptake (VO(2)) kinetics at the onset of moderate-intensity (80% ventilation threshold), constant-work rate exercise in eight older (65 +/- 2 yr) and seven younger adults (26 +/- 1 yr). Step increases in work rate from loadless cycling to moderate exercise (Mod(1)), heavy exercise, and moderate exercise (Mod(2)) were performed. Each exercise bout was 6 min in duration and separated by 6 min of loadless cycling. VO(2) kinetics were modeled from the onset of exercise by use of a two-component exponential model. Heart rate (HR) kinetics were modeled from the onset of exercise using a single exponential model. During Mod(1), the time constant (tau) for the predominant rise in VO(2) (tau VO(2)) was slower (P < 0.05) in the older adults (50 +/- 10 s) than in young adults (19 +/- 5 s). The older adults demonstrated a speeding (P < 0.05) of VO(2) kinetics when moderate-intensity exercise (Mod(2)) was preceded by high-intensity warm-up exercise (tau VO(2), 27 +/- 3 s), whereas young adults showed no speeding of VO(2) kinetics (tau VO(2), 17 +/- 3 s). In the older and younger adults, baseline HR preceding Mod(2) was elevated compared with Mod(1), but the tau for HR kinetics was slowed (P < 0.05) in Mod(2) only for the older adults. Prior heavy-intensity exercise in old, but not young, adults speeded VO(2) kinetics during Mod(2). Despite slowed HR kinetics in Mod(2) in the older adults, an elevated baseline HR before the onset of Mod(2) may have led to sufficient muscle perfusion and O(2) delivery. These results suggest that, when muscle blood flow and O(2) delivery are adequate, muscle O(2) consumption in both old and young adults is limited by intracellular processes within the exercising muscle.     

Relationships between muscle mitochondrial DNA content, mitochondrial enzyme activity and oxidative capacity in man: alterations with disease

Muscle mitochondrial content is tightly regulated, and requires the expression of both nuclear and mitochondrial genes. In addition, muscle mitochondrial content is a major determinant of aerobic exercise capacity in healthy subjects. The current study was designed to test the hypothesis that in healthy humans, muscle mitochondrial DNA (mtDNA) content is correlated with citrate synthase activity (a representative nuclear-encoded mitochondrial enzyme) and aerobic exercise capacity as defined by whole-body peak oxygen consumption (VO2). Furthermore, it was postulated that these relationships might be altered with disease. Twelve healthy and five paraplegic subjects underwent exercise testing and vastus lateralis muscle biopsy sampling. An additional ten healthy subjects and eight patients with unilateral peripheral arterial disease (PAD) underwent exercise testing and gastrocnemius muscle biopsy sampling. Citrate synthase activity and mtDNA content were positively correlated in the vastus lateralis muscles from the healthy subjects. This relationship was similar in muscle from paraplegic subjects. mtDNA content was positively correlated with peak VO2 in the healthy subjects and in the paraplegic subjects in whom peak VO2 had been elicited by functional electrical stimulation of the muscle. In contrast, the PAD subjects demonstrated higher mtDNA contents than would have been predicted based on their claudication-limited peak VO2. Thus, in healthy humans there are strong relationships between muscle mtDNA content and both muscle citrate synthase activity and peak VO2. These relationships are consistent with coordinant nuclear DNA and mtDNA expression, and with mitochondrial content being a determinant of aerobic exercise capacity. The relationships seen in healthy humans are quantitatively similar in paraplegic patients, but not in patients with PAD, a disease which is associated with a metabolic myopathy. The relationships between mtDNA content, mitochondrial enzyme activities and exercise capacity provide insight into the physiologic and pathophysiologic regulation of muscle mitochondrial expression.     

Comparison of oxygen uptake kinetics during concentric and eccentric cycle exercise.

O2 uptake (VO2) kinetics and electromyographic (EMG) activity from the vastus medialis, rectus femoris, biceps femoris, and medial gastrocnemius muscles were studied during constant-load concentric and eccentric cycling. Six healthy men performed transitions from baseline to high-intensity eccentric (HE) exercise and to high-intensity (HC), moderate-intensity (MC), and low-intensity (LC) concentric exercise. For HE and HC exercise, absolute work rate was equivalent. For HE and LC exercise, VO2 was equivalent. VO2 data were fit by a two- or three-component exponential model. Surface EMG was recorded during the last 12 s of each minute of exercise to obtain integrated EMG and mean power frequency. Only in the HC exercise did VO2 increase progressively with evidence of a slow component (phase 3), and only in HC exercise was there evidence of a coincident increase with time in integrated EMG of the vastus medialis and rectus femoris muscles (P < 0.05) with no change in mean power frequency. The phase 2 time constant was slower in HC [24.0 +/- 1.7 (SE) s] than in HE (14.7 +/- 2.8 s) and LC (16.7 +/- 2.2 s) exercise, while it was not different from MC exercise (20.6 +/- 2.1 s). These results show that the rate of increase in VO2 at the onset of exercise was not different between HE and LC exercise, where the metabolic demand was similar, but both had significantly faster kinetics for VO2 than HC exercise. The VO2 slow component might be related to increased muscle activation, which is a function of metabolic demand and not absolute work rate.     

Kinetics of muscle deoxygenation are accelerated at the onset of heavy-intensity exercise in patients with COPD: relationship to central cardiovascular dynamics.

Patients with chronic obstructive pulmonary disease (COPD) have slowed pulmonary O(2) uptake (Vo(2)(p)) kinetics during exercise, which may stem from inadequate muscle O(2) delivery. However, it is currently unknown how COPD impacts the dynamic relationship between systemic and microvascular O(2) delivery to uptake during exercise. We tested the hypothesis that, along with slowed Vo(2)(p) kinetics, COPD patients have faster dynamics of muscle deoxygenation, but slower kinetics of cardiac output (Qt) following the onset of heavy-intensity exercise. We measured Vo(2)(p), Qt (impedance cardiography), and muscle deoxygenation (near-infrared spectroscopy) during heavy-intensity exercise performed to the limit of tolerance by 10 patients with moderate-to-severe COPD and 11 age-matched sedentary controls. Variables were analyzed by standard nonlinear regression equations. Time to exercise intolerance was significantly (P < 0.05) lower in patients and related to the kinetics of Vo(2)(p) (r = -0.70; P < 0.05). Compared with controls, COPD patients displayed slower kinetics of Vo(2)(p) (42 +/- 13 vs. 73 +/- 24 s) and Qt (67 +/- 11 vs. 96 +/- 32 s), and faster overall kinetics of muscle deoxy-Hb (19.9 +/- 2.4 vs. 16.5 +/- 3.4 s). Consequently, the time constant ratio of O(2) uptake to mean response time of deoxy-Hb concentration was significantly greater in patients, suggesting a slower kinetics of microvascular O(2) delivery. In conclusion, our data show that patients with moderate-to-severe COPD have impaired central and peripheral cardiovascular adjustments following the onset of heavy-intensity exercise. These cardiocirculatory disturbances negatively impact the dynamic matching of O(2) delivery and utilization and may contribute to the slower Vo(2)(p) kinetics compared with age-matched controls.     

Skeletal muscle carnitine metabolism in patients with unilateral peripheral arterial disease.

Patients with peripheral arterial disease (PAD) have abnormalities of carnitine metabolism that may contribute to their functional impairment. To test the hypothesis that muscle acylcarnitine generation (intermediates in oxidative metabolism) in patients with PAD provides a marker of the muscle dysfunction, 10 patients with unilateral PAD and 6 age-matched control subjects were studied at rest, and the patients were studied during exercise. At rest, biopsies of the gastrocnemius muscle in the patients' nonsymptomatic leg revealed a normal carnitine pool and lactate content compared with control subjects. In contrast, the patients' diseased leg had higher contents of lactate and long-chain acylcarnitines than controls. The muscle short-chain acylcarnitine content in the patients' diseased leg at rest was inversely correlated with peak exercise performance (r = -0.75, P less than 0.05). With graded treadmill exercise, only patients who exceeded their individual lactate threshold had an increase in muscle short-chain acylcarnitine content in the nonsymptomatic leg, which was identical to the muscle carnitine response in normal subjects. In the patients' diseased leg, muscle short-chain acylcarnitine content increased with exercise from 440 +/- 130 to 900 +/- 200 (SE) nmol/g (P less than 0.05). In contrast to the nonsymptomatic leg, there was no increase in muscle lactate content in the diseased leg with exercise, and the change in muscle carnitine metabolism was correlated with exercise duration (r = 0.82, P less than 0.01) and not with the lactate threshold. We conclude that energy metabolism in ischemic muscle of patients with PAD is characterized by the accumulation of acylcarnitines.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of inspiratory threshold loading on ventilatory kinetics during constant-load exercise

Humoral factors play an important role in the control of exercise hyperpnea. The role of neuromechanical ventilatory factors, however, is still being investigated. We tested the hypothesis that the afferents of the thoracopulmonary system, and consequently of the neuromechanical ventilatory loop, have an influence on the kinetics of oxygen consumption (VO2), carbon dioxide output (VCO2), and ventilation (VE) during moderate intensity exercise. We did this by comparing the ventilatory time constants (tau) of exercise with and without an inspiratory load. Fourteen healthy, trained men (age 22.6 +/- 3.2 yr) performed a continuous incremental cycle exercise test to determine maximal oxygen uptake (VO2max = 55.2 +/- 5.8 ml x min(-1) x kg(-1)). On another day, after unloaded warm-up they performed randomized constant-load tests at 40% of their VO2max for 8 min, one with and the other without an inspiratory threshold load of 15 cmH2O. Ventilatory variables were obtained breath by breath. Phase 2 ventilatory kinetics (VO2, VCO2, and VE) could be described in all cases by a monoexponential function. The bootstrap method revealed small coefficients of variation for the model parameters, indicating an accurate determination for all parameters. Paired Student's t-tests showed that the addition of the inspiratory resistance significantly increased the tau during phase 2 of VO2 (43.1 +/- 8.6 vs. 60.9 +/- 14.1 s; P < 0.001), VCO2 (60.3 +/- 17.6 vs. 84.5 +/- 18.1 s; P < 0.001) and VE (59.4 +/- 16.1 vs. 85.9 +/- 17.1 s; P < 0.001). The average rise in tau was 41.3% for VO2, 40.1% for VCO2, and 44.6% for VE. The tau changes indicated that neuromechanical ventilatory factors play a role in the ventilatory response to moderate exercise.     

Slow upward drift of VO2 during constant-load cycling in untrained subjects

The oxygen uptake kinetics during constant-load exercise when sitting on a bicycle ergometer were determined in 7 untrained subjects by measuring breath-by-breath VO2 during continuous exercise to volitional exhaustion (mean endurance time = 1160 +/- 172 s) at a pedal frequency of 70 revolutions.min-1. The power output, averaging 189.5 W, was set at 82.5% of that eliciting the individual VO2max during a 5 min incremental exercise test. Throughout the exercise period, the VO2 kinetics could be appropriately described by a two-component exponential equation of the form: VO2(t) = Ya[1 - exp(-kat)] + Yb[1 - exp(-kbt)] where VO2 is net oxygen consumption and t the time from work onset. VO2 measured at the end of exercise was close to VO2max (98% VO2max) and the mean values of Ya, ka, Yb and kb amounted to 1195 ml O2.min-1, 0.034 s-1, 1562 ml O2.min-1, and 0.005 s-1 respectively. The initial rate of increase in VO2 predicted from the above equation is slower than that calculated, for the same work intensity, on the basis of the data obtained by Morton (1985) in trained subjects. For t greater than 480 s, however, the two models yield substantially equal results.     

VO(2) kinetics reveal a central limitation at the onset of subthreshold exercise in heart transplant recipients.

Because the cardiocirculatory response of heart transplant recipients (HTR) to exercise is delayed, we hypothesized that their O(2) uptake (VO(2)) kinetics at the onset of subthreshold exercise are slowed because of an impaired early "cardiodynamic" phase 1, rather than an abnormal subsequent "metabolic" phase 2. Thus we compared the VO(2) kinetics in 10 HTR submitted to six identical 10-min square-wave exercises set at 75% (36 +/- 5 W) of the load at their ventilatory threshold (VT) to those of 10 controls (C) similarly exercising at the same absolute (40 W; C40W group) and relative load (67 +/- 14 W; C67W group). Time-averaged heart rate, breath-by-breath VO(2), and O(2) pulse (O(2)p) data yielded monoexponential time constants of the VO(2) (s) and O(2)p increase. Separating phase 1 and 2 data permitted assessment of the phase 1 duration and phase 2 VO(2) time constant (). The VO(2) time constant was higher in HTR (38.4 +/- 7.5) than in C40W (22.9 +/- 9.6; P < or = 0. 002) or C67W (30.8 +/- 8.2; P < or = 0.05), as was the O(2)p time constant, resulting from a lower phase 1 VO(2) increase (287 +/- 59 vs. 349 +/- 66 ml/min; P < or = 0.05), O(2)p increase (2.8 +/- 0.6 vs. 3.6 +/- 1.0 ml/beat; P < or = 0.0001), and a longer phase 1 duration (36.7 +/- 12.3 vs. 26.8 +/- 6.0 s; P < or = 0.05), whereas the was similar in HTR and C (31.4 +/- 9.6 vs. 29.9 +/- 5.6 s; P = 0.85). Thus the HTR have slower subthreshold VO(2) kinetics due to an abnormal phase 1, suggesting that the heart is unable to increase its output abruptly when exercise begins. We expected a faster in HTR because of their prolonged phase 1 duration. Because this was not the case, their muscular metabolism may also be impaired at the onset of subthreshold exercise.     

Iron deficiency anemia and steady-state work performance at high altitude

Thirty-seven young adult male highland residents at 3,600-4,100 m in La Paz, Bolivia, performed short-duration cycle ergometry at 60, 80, and 100% of maximal voluntary O2 consumption (VO2max). Three groups of subjects representing the high-altitude population mean hemoglobin (Hb), the 10th percentile Hb, and below the 1st percentile were examined to test the hypothesis that the relationship of exercise performance to Hb concentration is similar to those relationships established at low altitude. Anemic individuals (n = 8) had 23% lower voluntary VO2max and 28% lower maximal work loads compared with controls (n = 17) or marginally anemic subjects (n = 12) although the relationship of VO2 to work load was similar. Anemic individuals maintained significantly higher arterial O2 partial pressures and Hb saturations during heavy exercise (90 +/- 0.5 vs. 85 +/- 0.6%) in conjunction with a greater heart rate up to maximal effort. A significantly decreased erythrocyte 2,3-diphosphoglycerate (2,3-DPG)-to-Hb molar ratio (0.70 +/- 0.04 vs. 1.12 +/- 0.06), suggestive of a left-shifted dissociation curve in anemics, is in contrast to the expected right-shifted curve. Moderate anemics were similar to controls. Anemic individuals did not differ in arterial lactate concentration from controls at absolute work loads; anemics had significantly lower arterial lactate concentrations at maximal effort than controls with no differences in the work load-to-lactate relationship. In conclusion, O2 transport during exercise at high altitude seems unaffected by the Hb concentrations as low as the 10th percentile of the population mean.(ABSTRACT TRUNCATED AT 250 WORDS)     

Place of muscular exercise test in screening in asymptomatic smokers

The diagnosis of smoking-related chronic obstructive pulmonary disease (COPD) is often made too late. Could the study of breathing pattern during exercise testing help in earlier detection. In order to test this hypothesis, we studied 34 asymptomatic smokers (S) compared to 55 nonsmoking controls (NS). The subjects, divided into 3 age groups (30-60 yr), were comparable in terms of anthropometric and spirometric characteristics. The smokers from 30-50 yr had a lower VO2max than the controls (p less than 0.01) whereas the older smokers (50-60 yr) had a VO2max comparable to that of the controls. The study of breathing pattern indicated rapid, shallow breathing by all smokers. Thus exercise testing, and the abnormalities observed in breathing pattern, would seem to help in early detection of COPD in asymptomatic smokers.     

Maximum oxygen uptake and arterial blood oxygenation during hypoxic exercise in rats.

The objectives of these experiments were 1) to describe the effect of maximum treadmill exercise on gas exchange, arterial blood gases, and arterial blood oxygenation in rats acclimated for 3 wk to simulated altitude (SA, barometric pressure 370-380 Torr) and 2) to determine the contribution of acid-base changes to the changes in arterial blood oxygenation of hypoxic exercise. Maximum O2 uptake (VO2max) was measured in four groups of rats: 1) normoxic controls run in normoxia (Nx), 2) normoxic controls run in acute hypoxia [AHx inspiratory PO2 (PIO2) approximately 70 Torr], 3) SA rats run in hypoxia (3WHx, PIO2 approximately 70 Torr), and 4) SA rats run in normoxia (ANx). VO2max (ml STPD.min-1.kg-1) was 70.8 +/- 0.9 in Nx, 46.4 +/- 1.9 in AHx, 52.6 +/- 1.1 in 3WHx, and 70.0 +/- 2.4 in ANx. Exercise resulted in acidosis, hypocapnia, and elevated blood lactate in all groups. Although blood lactate increased less in 3WHx and ANx, pH was the same or lower than in Nx and AHx, reflecting the low buffer capacity of SA. In AHx and 3WHx, arterial PO2 increased with exercise; however, O2 saturation of hemoglobin in arterial blood (SaO2) decreased. In vitro measurements of the Bohr shift suggest that SaO2 decreased as a result of a decrease in hemoglobin O2 affinity. The data indicate that several features of hypoxic exercise in this model are similar to those seen in humans, with the exception of the mechanism of decrease in SaO2, which, in humans, appears to be due to incomplete alveolar-capillary equilibration.     

Progressive recruitment of muscle fibers is not necessary for the slow component of VO2 kinetics.

The "slow component" of O2 uptake (VO2) kinetics during constant-load heavy-intensity exercise is traditionally thought to derive from a progressive recruitment of muscle fibers. In this study, which represents a reanalysis of data taken from a previous study by our group (Grassi B, Hogan MC, Greenhaff PL, Hamann JJ, Kelley KM, Aschenbach WG, Constantin-Teodosiu D, Gladden LB. J Physiol 538: 195-207, 2002) we evaluated the presence of a slow component-like response in the isolated dog gastrocnemius in situ (n=6) during 4 min of contractions at approximately 60-70% of peak VO2. In this preparation all muscle fibers are maximally activated by electrical stimulation from the beginning of the contraction period, and no progressive recruitment of fibers is possible. Muscle VO2 was calculated as blood flow multiplied by arteriovenous O2 content difference. The muscle fatigued (force decreased by approximately 20-25%) during contractions. Kinetics of adjustment were evaluated for 1) VO2, uncorrected for force development; 2) VO2 normalized for peak force; 3) VO2 normalized for force-time integral. A slow component-like response, described in only one muscle out of six when uncorrected VO2 was considered, was observed in all muscles when VO2/peak force and VO2/force-time were considered. The amplitude of the slow component-like response, expressed as a fraction of the total response, was higher for VO2/peak force (0.18+/-0.06, means+/-SE) and for VO2/force-time (0.22+/-0.05) compared with uncorrected VO2 (0.04+/-0.04). A progressive recruitment of muscle fibers may not be necessary for the development of the slow component of VO2 kinetics, which may be caused by the metabolic factors that induce muscle fatigue and, as a consequence, reduce the efficiency of muscle contractions.     

Control of ventilation during exercise in patients with central venous-to-systemic arterial shunts

The diversion of systemic venous blood into the arterial circulation in patients with intracardiac right-to-left shunts represents a pathophysiological condition in which there are alterations in some of the potential stimuli for the exercise hyperpnea. We therefore studied 18 adult patients with congenital (16) or noncongenital (2) right-to-left shunts and a group of normal control subjects during constant work rate and progressive work rate exercise to assess the effects of these alterations on the dynamics of exercise ventilation and gas exchange. Minute ventilation (VE) was significantly higher in the patients than in the controls, both at rest (10.7 +/- 2.4 vs. 7.5 +/- 1.2 l/min, respectively) and during constant-load exercise (24.9 +/- 4.8 vs. 12.7 +/- 2.61 l/min, respectively). When beginning constant work rate exercise from rest, the ventilatory response of the patients followed a pattern that was distinct from that of the normal subjects. At the onset of exercise, the patients' end-tidal PCO2 decreased, end-tidal PO2 increased, and gas exchange ratio increased, indicating that pulmonary blood was hyperventilated relative to the resting state. However, arterial blood gases, in six patients in which they were measured, revealed that despite the large VE response to exercise, arterial pH and PCO2 were not significantly different from resting values when sampled during the first 2 min of moderate-intensity exercise. Arterial PCO2 changed by an average of only 1.4 Torr after 4.5-6 min of exercise. Thus the exercise-induced alveolar and pulmonary capillary hypocapnia was of an appropriate degree to compensate for the shunting of CO2-rich venous blood into the systemic arterial circulation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Enhanced endothelium-dependent vasodilation in older endurance-trained men.

We hypothesized that abnormal endothelium-dependent vasodilation (EDD) found in older otherwise healthy subjects can be attenuated with long-term endurance training. Ten endurance-trained men, 68.5 +/- 2.3 yr old, and 10 healthy sedentary men, 64.7 +/- 1.4 yr old, were studied. Aerobic exercise capacity (VO(2 max)), fasting plasma cholesterol, insulin, and homocysteine concentrations were measured. Master athletes had higher VO(2 max) (42 +/- 2.3 vs. 27 +/- 1.4 ml. kg(-1). min(-1), P < 0.001), slightly higher total cholesterol (226 +/- 8 vs. 199 +/- 8 mg/dl, P = 0.05), similar insulin, and higher homocysteine (10.7 +/- 1.3 vs. 9.2 +/- 1.4 micromol/ml, p = 0.02) concentrations. Brachial arterial diameter, determined with vascular ultrasound, during the hyperemic response was greater in the master athletes than in controls (P = 0.005). Peak vasodilatory response was 109.1 +/- 2 vs. 103.6 +/- 2% (P < 0.05) in the athletes and controls, respectively. Endothelium-independent vasodilation in response to nitroglycerin was similar between the two groups. The increased arterial diameter during the hyperemic response correlated significantly with the VO(2 max) in the entire population (r = 0.66, P < 0.002). Our results suggest that long-term endurance exercise training in older men is associated with systemic enhanced EDD, which is even detectable in the conduit arteries of untrained muscle.     

Ventilatory and metabolic adaptations to walking and cycling in patients with COPD.

To test the hypothesis that in chronic obstructive pulmonary disease (COPD) patients the ventilatory and metabolic requirements during cycling and walking exercise are different, paralleling the level of breathlessness, we studied nine patients with moderate to severe, stable COPD. Each subject underwent two exercise protocols: a 1-min incremental cycle ergometer exercise (C) and a "shuttle" walking test (W). Oxygen uptake (VO(2)), CO(2) output (VCO(2)), minute ventilation (VE), and heart rate (HR) were measured with a portable telemetric system. Venous blood lactates were monitored. Measurements of arterial blood gases and pH were obtained in seven patients. Physiological dead space-tidal volume ratio (VD/VT) was computed. At peak exercise, W vs. C VO(2), VE, and HR values were similar, whereas VCO(2) (848 +/- 69 vs. 1,225 +/- 45 ml/min; P < 0. 001) and lactate (1.5 +/- 0.2 vs. 4.1 +/- 0.2 meq/l; P < 0.001) were lower, DeltaVE/DeltaVCO(2) (35.7 +/- 1.7 vs. 25.9 +/- 1.3; P < 0. 001) and DeltaHR/DeltaVO(2) values (51 +/- 3 vs. 40 +/- 4; P < 0.05) were significantly higher. Analyses of arterial blood gases at peak exercise revealed higher VD/VT and lower arterial partial pressure of oxygen values for W compared with C. In COPD, reduced walking capacity is associated with an excessively high ventilatory demand. Decreased pulmonary gas exchange efficiency and arterial hypoxemia are likely to be responsible for the observed findings.     

Endothelial function in highly endurance-trained men: effects of acute exercise

Exercise training reverses endothelial dysfunction, but the effect in young, healthy subjects is less clear. We determined the influence of maximal oxygen uptake (VO2max) and a single bout of high-intensity exercise on flow-mediated dilatation (FMD), brachial artery diameter, peak blood flow, nitric oxide (NO) bioavailability, and antioxidant status in highly endurance-trained men and their sedentary counterparts. Ten men athletes (mean +/- SEM age 23.5 +/- 0.9 years, height 182.6 +/- 2.4 cm, weight 72.5 +/- 2.4 kg, VO2max 75.9 +/- 0.8 mL.kg.min) and seven healthy controls (age 25.4 +/- 1.2 years, height 183.9 +/- 3.74 cm, weight 92.8 +/- 3.9 kg, VO2max 47.7 +/- 1.7 mL.kg.min) took part in the study. FMD, brachial artery diameter, and peak blood flow were measured using echo-Doppler before, 1 hour, 24 hours, and 48 hours after a single bout of interval running for 5 x 5 minutes at 90% of maximal heart rate. NO bioavailability and antioxidant status in blood were measured at all time points. Maximal arterial diameter and peak flow were 10-15% (P < 0.02) and 28-35% (P < 0.02) larger, respectively, in athletes vs. controls at all time points, and similar FMD were observed, apart from a transient decay of FMD in athletes 1 hour post exercise. NO bioavailability increased significantly after exercise in both groups and decreased to baseline levels after 24 hours in controls but remained increased 80% and 93% above baseline 24 and 48 hours post exercise in athletes. Antioxidant status was equal in the two groups at baseline and increased by approximately 10% 1 hour post exercise, an effect that lasted for 24 hours. Athletes had larger arterial diameter but similar FMD as untrained subjects, i.e., athletes had larger capacity for blood transport compared with their untrained counterparts. The observed FMD, bioavailability of NO, and antioxidant status in blood were highly dependent on the time elapsed after the exercise session.