Allometric scaling of flow-mediated dilation: is it always helpful?

Flow-mediated dilation (FMD) is calculated as the greatest percent change in arterial diameter following an ischaemic challenge. This Traditional %FMD calculation is thought to have statistical bias towards baseline diameter (Dbase ), which is reduced by allometric scaling. This study examined whether allometric scaling FMD influenced the difference between a group of healthy young and older adults compared to the Traditional %FMD, and to determine whether a New (allometric) scaling %FMD improved the ability to obtain individually scaled FMD. Popliteal artery FMD was assessed in 18 young (26 ± 3 years) and 17 older adults (77 ± 5 years). 'Corrected' mean FMD was generated from a log-linked ANCOVA model. Individual %FMD was evaluated using three calculations: (1) Traditional %FMD calculation; (2) Atkinson (allometric) scaling %FMD (peak diameter (Dpeak)/(Dbasescalingexponent)); and (3) New scaling %FMD ((Dpeak-Dbase)/(Dbasescalingexponent)). Traditional %FMD was significantly larger in young (5·82 ± 2·58%) versus old (3·72 ± 1·26%). 'Corrected' FMD means (Y: 5·97 ± 2·12%; O: 3·98 ± 2·06%) were similar to Traditional %FMD; however, the logarithmic transformation prevents statistical interpretation of group differences. Individually scaled %FMD using the Atkinson scaling resulted in values that were corrected for variations in Dbase but that were twofold to threefold larger than those of the Traditional calculation. New scaling %FMD resulted in values that were similar to values expected (Y: 6·21 ± 2·75%; O: 3·98 ± 1·36%); however, it did not effectively correct for variation in Dbase . Recommendations regarding the advantages of allometrically scaling %FMD should be made with caution until research clearly establishes the benefits of this approach.

Effects of short-term training and detraining on VO2 kinetics: Faster VO2 kinetics response after one training session.

This study examined the time course of short-term training and detraining-induced changes in oxygen uptake ( V ˙ O 2 ) kinetics. Twelve men (24 ± 3 years) were assigned to either a 50% or a 70% of V ˙ O 2 m a x training intensity (n = 6 per group). V ˙ O 2 was measured breath-by-breath. Changes in deoxygenated-hemoglobin concentration (Δ[HHb]) were measured by near-infrared spectroscopy. Moderate-intensity exercise on-transient V ˙ O 2 and Δ[HHb] were modeled with a mono-exponential and normalized (0-100% of response) and the [ H H b ] / V ˙ O 2 ratio was calculated. Similar changes in time constant of V ˙ O 2 ( t V ˙ O 2 ) were observed in both groups. The combined group mean for t V ˙ O 2 decreased ∼14% (32.3 to 27.9 s, P < 0.05) after one training session with a further ∼11% decrease (27.9 to 24.8 s, P < 0.05) following two training sessions. The t V ˙ O 2 p remained unchanged throughout the remaining of training and detraining. A significant "overshoot" in the [ H H b ] / V ˙ O 2 ratio was decreased (albeit not significant) after one training session, and abolished (P < 0.05) after the second one, with no overshoot observed thereafter. Speeding of V ˙ O 2 kinetics was remarkably quick with no further changes being observed with continuous training or during detraining. Improve matching of local O2 delivery to O2 utilization is a mechanism proposed to influence this response.

The independent roles of cardiorespiratory fitness and sedentary time on chronic conditions and Body Mass Index in older adults.

AIM: The aim of this paper was to examine the independent influence of cardiorespiratory fitness and sedentary behavior on chronic disease incidence and body composition in older adults. METHODS: A sample of 292 community dwelling men and women (mean 69.3±8.1 years) underwent maximal treadmill testing and completed questionnaires relating to their leisure-time physical activity, sedentary time, and health. RESULTS: The average V O2 of the sample was approximately 21 ml.kg(-1).min(-1) with the average sedentary time being over 3 hours per day. Cardiorespiratory fitness was found to be a stronger predictor of number of chronic conditions and BMI than total physical activity and sedentary. Those with a higher cardiorespiratory fitness had fewer chronic conditions and a lower BMI. No such associations were seen for either total physical activity levels or sedentary time. CONCLUSION: Cardiorespiratory fitness is a stronger predictor of health among older adults and further highlights the importance of promoting public health guidelines for cardiorespiratory fitness.

Effect of high-fat and high-carbohydrate diets on pulmonary O2 uptake kinetics during the transition to moderate-intensity exercise.

Mitochondrial pyruvate dehydrogenase (PDH) regulates the delivery of carbohydrate-derived substrate to the mitochondrial tricarboxylic acid cycle and electron transport chain. PDH activity at rest and its activation during exercise is attenuated following high-fat (HFAT) compared with high-carbohydrate (HCHO) diets. Given the reliance on carbohydrate-derived substrate early in transitions to exercise, this study examined the effects of HFAT and HCHO on phase II pulmonary O2 uptake (V̇o2 p) kinetics during transitions into the moderate-intensity (MOD) exercise domain. Eight active adult men underwent dietary manipulations consisting of 6 days of HFAT (73% fat, 22% protein, 5% carbohydrate) followed immediately by 6 days of HCHO (10% fat, 10% protein, 80% carbohydrate); each dietary phase was preceded by a glycogen depletion protocol. Participants performed three MOD transitions from a 20 W cycling baseline to work rate equivalent to 80% of estimated lactate threshold on days 5 and 6 of each diet. Steady-state V̇o2 p was greater (P < 0.05), and respiratory exchange ratio and carbohydrate oxidation rates were lower (P < 0.05) during HFAT. The phase II V̇o2 p time constant (τV̇o2 p) [HFAT 40 ± 16, HCHO 32 ± 19 s (mean ± SD)] and V̇o2 p gain (HFAT 10.3 ± 0.8, HCHO 9.4 ± 0.7 ml·min(-1·)W(-1)) were greater (P < 0.05) in HFAT. The overall adjustment (effective time constant) of muscle deoxygenation (Δ[HHb]) was not different between diets (HFAT 24 ± 4 s, HCHO 23 ± 4 s), which coupled with a slower τV̇o2 p, indicates a slowed microvascular blood flow response. These results suggest that the slower V̇o2 p kinetics associated with HFAT are consistent with inhibition and slower activation of PDH, a lower rate of pyruvate production, and/or attenuated microvascular blood flow and O2 delivery.

O2 uptake kinetics, pyruvate dehydrogenase activity, and muscle deoxygenation in young and older adults during the transition to moderate-intensity exercise.

The adaptation of pulmonary O(2) uptake (Vo(2)(p)) kinetics is slowed in older compared with young adults during the transition to moderate-intensity exercise. In this study, we examined the relationship between Vo(2)(p) kinetics and mitochondrial pyruvate dehydrogenase (PDH) activity in young (n = 7) and older (n = 6) adults. Subjects performed cycle exercise to a work rate corresponding to approximately 90% of estimated lactate threshold. Phase 2 Vo(2)(p) kinetics were slower (P < 0.05) in older (tau = 40 +/- 17 s) compared with young (tau = 21 +/- 6 s) adults. Relative phosphocreatine (PCr) breakdown was greater (P < 0.05) at 30 s in older compared with young adults. Absolute PCr breakdown at 6 min was greater (P < 0.05) in older compared with young adults. In young adults, PDH activity increased (P < 0.05) from baseline to 30 s, with no further change observed at 6 min. In older adults, PDH activity during baseline exercise was similar to that seen in young adults. During the exercise transition, PDH activity did not increase (P > 0.05) at 30 s of exercise but was elevated (P < 0.05) after 6 min. The change in deoxyhemoglobin (HHb) was greater for a given Vo(2)(p) in older adults, and there was a similar time course of HHb accompanying the slower Vo(2)(p) kinetics in the older adults, suggesting a slower adaptation of bulk O(2) delivery in older adults. In conclusion, the slower adaptation of Vo(2)(p) in older adults is likely a result of both an increased metabolic inertia and lower O(2) availability.

O2 uptake and muscle deoxygenation kinetics during the transition to moderate-intensity exercise in different phases of the menstrual cycle in young adult females.

O(2) uptake (VO2) kinetics were examined during the follicular (F) and luteal (L) phases of the menstrual cycle to determine if there was an effect of altered sex hormones on the (VO2) response to moderate-intensity exercise. Seven healthy women (age 21 +/- 2 years; mean +/- SD) performed six transitions from 20 W to moderate-intensity exercise (approximately 90% theta L) during the F and L phase. VO2 was measured breath-by-breath and deoxyhemoglobin/myoglobin (Delta HHb) was determined by near infrared spectroscopy. Progesterone and estrogen were significantly (P < 0.05) elevated during the L compared to F phase. VO2 kinetics (tau VO2) were not different in the two phases of the menstrual cycle (F, 22 +/- 5 s; L, 22 +/- 6 s; 95% confidence intervals +/-4 s) nor was the time course of the Delta HHb response (F, TD 11 +/- 2 s, tau 11 +/- 3 s; L, TD 12 +/- 2 s, tau 12 +/- 11 s; tau HHb 95% confidence intervals +/-3 s). Respiratory exchange ratio (RER) was not different between phases for baseline or steady-state exercise and the blood lactate response to exercise was not different. In conclusion, VO2 kinetics at the onset of moderate-intensity exercise are not affected by the phase of the menstrual cycle in young females suggesting either no change in, or no effect of metabolic activation on the on-transient kinetics of moderate-intensity exercise. Additionally, the similar adaptation of Delta HHb in combination with unchanged VO2 suggests that there were no differences in the adaptation of local muscle O(2) delivery.

Prior heavy exercise elevates pyruvate dehydrogenase activity and speeds O2 uptake kinetics during subsequent moderate-intensity exercise in healthy young adults.

The adaptation of pulmonary oxygen uptake (.VO2) during the transition to moderate-intensity exercise (Mod) is faster following a prior bout of heavy-intensity exercise. In the present study we examined the activation of pyruvate dehydrogenase (PDHa) during Mod both with and without prior heavy-intensity exercise. Subjects (n = 9) performed a Mod(1)-heavy-intensity-Mod(2) exercise protocol preceded by 20 W baseline. Breath-by-breath .VO2 kinetics and near-infrared spectroscopy-derived muscle oxygenation were measured continuously, and muscle biopsy samples were taken at specific times during the transition to Mod. In Mod(1), PDHa increased from baseline (1.08 +/- 0.2 mmol min(-1) (kg wet wt)(-1)) to 30 s (2.05 +/- 0.2 mmol min(-1) (kg wet wt)(-1)), with no additional change at 6 min exercise (2.07 +/- 0.3 mmol min(-1) (kg wet wt)(-1)). In Mod(2), PDHa was already elevated at baseline (1.88 +/- 0.3 mmol min(-1) (kg wet wt)(-1)) and was greater than in Mod(1), and did not change at 30 s (1.96 +/- 0.2 mmol min(-1) (kg wet wt)(-1)) but increased at 6 min exercise (2.70 +/- 0.3 mmol min(-1) (kg wet wt)(-1)). The time constant of .VO2 was lower in Mod(2) (19 +/- 2 s) than Mod(1) (24 +/- 3 s). Phosphocreatine (PCr) breakdown from baseline to 30 s was greater (P < 0.05) in Mod(1) (13.6 +/- 6.7 mmol (kg dry wt)(-1)) than Mod(2) (6.5 +/- 6.2 mmol (kg dry wt)(-1)) but total PCr breakdown was similar between conditions (Mod(1), 14.8 +/- 7.4 mmol (kg dry wt)(-1); Mod(2), 20.1 +/- 8.0 mmol (kg dry wt)(-1)). Both oxyhaemoglobin and total haemoglobin were elevated prior to and throughout Mod(2) compared with Mod(1). In conclusion, the greater PDHa at baseline prior to Mod(2) compared with Mod(1) may have contributed in part to the faster .VO2 kinetics in Mod(2). That oxyhaemoglobin and total haemoglobin were elevated prior to Mod(2) suggests that greater muscle perfusion may also have contributed to the observed faster .VO2 kinetics. These findings are consistent with metabolic inertia, via delayed activation of PDH, in part limiting the adaptation of pulmonary .VO2 and muscle O2 consumption during the normal transition to exercise.

Determinants of oxygen uptake kinetics in older humans following single-limb endurance exercise training.

We hypothesised that the observed acceleration in the kinetics of exercise on-transient oxygen uptake (VO2) of five older humans (77 +/- 7 years (mean +/- S.D.) following 9 weeks of single-leg endurance exercise training was due to adaptations at the level of the muscle cell. Prior to, and following training, subjects performed constant-load single-limb knee extension exercise. Following training VO2 kinetics (phase 2, tau) were accelerated in the trained leg (week 0, 92 +/- 44 s; week 9, 48 +/- 22 s) and unchanged in the untrained leg (week 0, 104 +/- 43 s; week 9, 126 +/- 35 s). The kinetics of mean blood velocity in the femoral artery were faster than the kinetics of VO2, but were unchanged in both the trained (week 0, 19 +/- 10 s; week 9, 26 +/- 11 s) and untrained leg (week 0, 20 +/- 18 s; week 9, 18 +/- 10 s). Maximal citrate synthase activity, measured from biopsies of the vastus lateralis muscle, increased (P < 0.05) in the trained leg (week 0, 6.7 +/- 2.0 micromol x (g wet wt)(-1) x min(-1); week 9, 11.4 +/- 3.6 micromol x (g wet wt)(-1) x min(-1)) but was unchanged in the untrained leg (week 0, 5.9 +/- 0.5 micromol x (g wet wt)(-1) x min(-1); week 9, 7.9 +/- 1.9 micromol x (g wet wt)(-1) x min(-1)). These data suggest that the acceleration of VO2 kinetics was due to an improved rate of O2 utilisation by the muscle, but was not a result of increased O2 delivery.

A comparison of modelling techniques used to characterise oxygen uptake kinetics during the on-transient of exercise.

We compared estimates for the phase 2 time constant (tau) of oxygen uptake (VO2) during moderate- and heavy-intensity exercise, and the slow component of VO2 during heavy-intensity exercise using previously published exponential models. Estimates for tau and the slow component were different (P < 0.05) among models. For moderate-intensity exercise, a two-component exponential model, or a mono-exponential model fitted from 20 s to 3 min were best. For heavy-intensity exercise, a three-component model fitted throughout the entire 6 min bout of exercise, or a two-component model fitted from 20 s were best. When the time delays for the two- and three-component models were equal the best statistical fit was obtained; however, this model produced an inappropriately low DeltaVO2/DeltaWR (WR, work rate) for the projected phase 2 steady state, and the estimate of phase 2 tau was shortened compared with other models. The slow component was quantified as the difference between VO2 at end-exercise (6 min) and at 3 min (DeltaVO2 (6-3 min)); 259 ml x min(-1)), and also using the phase 3 amplitude terms (truncated to end-exercise) from exponential fits (409-833 ml x min(-1)). Onset of the slow component was identified by the phase 3 time delay parameter as being of delayed onset approximately 2 min (vs. arbitrary 3 min). Using this delay DeltaVO2 (6-2 min) was approximately 400 ml x min(-1). Use of valid consistent methods to estimate tau and the slow component in exercise are needed to advance physiological understanding.

Lung function in older humans: the contribution of body composition, physical activity and smoking.

An allometric model was used to determine the important factors related to the decline in forced expiratory volume (FEV1.0) across ages 55-86 years in independently living men and women. Measurements were available from a randomized sample of 181 men and 203 women residing in London, Ontario, Canada. The effects of height, age, sex, adiposity, fat free mass (FFM), grip strength and physical activity (PA) on FEV1.0 were assessed using an allometric model to test the hypothesis that sex differences in lung function would be due in part to sex-related differences in the aforementioned variables and would therefore be eliminated by our analysis. The following model was linearized and parameters were identified using standard multiple regression: FEV1.0 = height(beta1) x FFM(beta2) x grip strength(beta3) x PA(beta4) x exp(beta0 + beta5age + beta6sex + beta7smoking + beta8%body fat) x epsilon. Results indicate that the amount of FFM and heavy intensity physical activity participated in by the elderly may be more important in influencing forced expiratory function than previously recognized. In addition, results from this study have confirmed the importance of age and height in the prediction of FEV1.0 and demonstrated a negative effect of smoking on lung function. Individuals with a greater FFM and physical activity level tended to be associated with an above average lung function performance. The cross-sectional rate of decline in FEV1.0 determined from our model was approximately 12% per decade.

Dynamic ventilatory response to acute isocapnic hypoxia in septuagenarians.

This study compared the ventilatory response to 20 min of acute isocapnic hypoxia (end-tidal P(O(2)), 50 mmHg) using the technique of dynamic end-tidal forcing in young (Y) and old (O) men. Two groups of non-smoking male subjects (mean +/- s.d. age: Y, 29.8 +/- 6.9 years; O, 73.4 +/- 2.8 years) with similar body size, normal age-predicted spirometry, and normal moderate levels of physical activity were studied. Compared with baseline ventilation in euoxia (10.79 +/- 1.99 and 11.88 +/- 0.91 l min-1) both groups responded to the abrupt onset of isocapnic hypoxia with peak ventilatory responses of 22.58 +/- 2.60 and 24.56 +/- 2.54 l min-1 for Y and O, respectively (not significant, n.s.). Both groups demonstrated a significant increment in neuromuscular drive (i.e. tidal volume (V(T))/inspiratory time (T(I)); 0.46 +/- 0.06 to 0.91 +/- 0.15 and 0.48 +/- 0.06 to 0.91 +/- 0.12 l s-1 for Y and O, respectively) with a small (but also significant) change in central timing (T(I)/total ventilation time (T(tot)); 0.38 +/- 0.02 to 0.41 +/- 0.02 and 0.42 +/- 0.02 to 0.45 +/- 0.02 for Y and O, respectively). Oxygen sensitivity was assessed using Weil's equation, and gave a hyperbolic factor (A) of 282 +/- 75 and 317 +/- 72, and using the linear equation: change in expiratory minute volume (DeltaV.(E))/change in arterial O(2) saturation (DeltaS(a,O(2))) which gave -1.17 +/- 0.57 and -1.17 +/- 0.42 l min-1 %-1 (n.s.) for Y and O, respectively. After 20 min of sustained isocapnic hypoxia, ventilation declined to 14.29 +/- 1.92 and 16.85 +/- 2.34 l min-1 for Y and O, respectively (n.s.). The acute response to hypoxia was characterised by similar time constants (16.0 +/- 5.4 and 18.5 +/- 6.7 s) and time delays (4.8 +/- 2.1 and 4.6 +/- 1.9 s) for Y and O, respectively. Thus, the dynamic ventilatory response to acute isocapnic hypoxia is maintained into the eighth decade in a group of habitually active elderly men. Experimental Physiology (2001) 86.1, 117-126.

A self-paced step test to predict aerobic fitness in older adults in the primary care clinic.

OBJECTIVES: To study the potential usefulness of a submaximal self-paced step test as a prediction of maximal aerobic capacity (VO2max) in older adults in the primary care setting. DESIGN: Data were collected during a prospective randomized study of an exercise program. SETTING: Four university family medical clinics in London, Ontario, Canada. PARTICIPANTS: A random sample of 240 healthy older (> or =65) men (n = 118) and women (n = 122) from four family medical clinics underwent self-paced step testing in the clinic with a family physician (n = 16), and step testing and a maximal exercise treadmill test with measurement of respired gases in an exercise laboratory. Testing was done in random order (clinic/laboratory) separated by 2 weeks and then repeated at 52 weeks, following introduction of an exercise program. Relationships between outcome variables were examined by Pearson correlation coefficients while prediction of VO2max was examined using multivariate regression analysis. Cross-validation with 30 age-matched hypertensive and 40 age-matched post-hip arthroplasty patients was used to test the accuracy of the predictive models. MEASUREMENTS: Measured VO2max, predicted VO2max, step test time, step test heart rate, body mass index (BMI), and O2 pulse. RESULTS: Two hundred women (n = 108) and men (n = 92) completed both the initial and 52-week assessments. Stepping time, heart rate, age, BMI, and O2 pulse were strongly associated with VO2max for both a normal and a fast step pace and were chosen to develop the predictive model. Normal step-pace correlation with VO2max (ml/kg/min) was no different (female 0.93: male 0.91) from fast pace (0.95:0.90) with no difference between clinic and laboratory measurement at baseline or 52 weeks. Cross-validation showed no significant difference from the main group using the predictive model. CONCLUSIONS: The self-paced step test is a safe and simple clinical instrument that strongly and reliably predicts VO2max, is sensitive to change, and is generalizable in the family practice setting among community-dwelling older adults differing in fitness and health status.

Left ventricular diastolic filling and cardiovascular functional capacity in older men.

We investigated anaerobic threshold (< theta(L)) gas exchange kinetics and maximal oxygen uptake (VO2,max) among older men with reduced left ventricular end-diastolic filling (LVDF). Ten men (mean age, 73 years) with LVDF impairment and low fitness, but without other cardiovascular dysfunction were studied. Treatments compared to control included: 5 days, high intensity exercise training protocol; 5 days, calcium channel blockade (240 mg verapamil); 21 days, detraining/washout; and 5 days, combined treatments. Results indicated no changes in resting left ventricular systolic function with any treatment. Significant resting diastolic function changes included increased early:late flow velocity (control, 0.87; training, 1.28; verapamil, 1.32), and a decreased isovolumic relaxation time (control, 0.10 s; training, 0.08 s; verapamil, 0.08 s). The combined treatments were not additive. Sub-threshold oxygen uptake kinetics (tauVO2, s) were significantly faster following either training or verapamil (tauVO2,control, 62+/-12; tauVO2,training, 44+/-9; tauVO2,verapamil, 48+/-10) and combined treatments (tauVO2, 41+/- 8). V O2,max (ml kg(-1) min(-1)) was significantly increased (control, 21.8+/-2.2; training, 27.3+/-2.2; verapamil, 25.2+/-3.4; combined treatments, 26.9+/-2.3). Increasing ventricular preload with either exercise training or calcium channel blockade was coincident with faster tauVO2 and increased VO2,max.

Forearm muscle metabolism studied using (31)P-MRS during progressive exercise to fatigue after Acz administration.

The effects of acetazolamide (Acz)-induced carbonic anhydrase inhibition (CAI) on muscle intracellular thresholds (T) for intracellular pH (pH(i)) and inorganic phosphate-to-phosphate creatine ratio (P(i)/PCr) and the plasma lactate (La(-)) threshold were examined in nine adult male subjects performing forearm wrist flexion exercise to fatigue. Exercise consisted of raising and lowering (1-s contraction, 1-s relaxation) a cylinder whose volume increased at a rate of 200 ml/min. The protocol was performed during control (Con) and after 45 min of CAI with Acz (10 mg/kg body wt iv). T(pH(i)) and T(P(i)/PCr), determined using (31)P-labeled magnetic resonance spectroscopy (MRS), were similar in Acz (722 +/- 50 and 796 +/- 75 mW, respectively) and Con (855 +/- 211 and 835 +/- 235 mW, respectively). The pH(i) was similar at end-exercise (6.38 +/- 0.10 Acz and 6.43 +/- 0.22 Con), but pH(i) recovery was slowed in Acz. In a separate experiment, blood was sampled from a deep arm vein at the elbow for determination of plasma lactate concentration ([La(-)](pl)) and T(La(-)). [La(-)](pl) was lower (P < 0.05) in Acz than Con (3.7 +/- 1.7 vs. 5.0 +/- 1.7 mmol/l) at end-exercise and in early recovery, but T(La(-)) was higher (1,433 +/- 243 vs. 1,041 +/- 414 mW, respectively). These data suggest that the lower [La(-)](pl) seen with CAI was not due to a delayed onset or rate of muscle La(-) accumulation but may be related to impaired La(-) removal from muscle.

The off-transient pulmonary oxygen uptake (VO(2)) kinetics following attainment of a particular VO(2) during heavy-intensity exercise in humans.

The oxygen uptake response to moderate-intensity exercise (i.e. < anaerobic threshold (an)) has been characterised with a gain (i.e. response amplitude per increment of work rate) and time constant that do not vary appreciably at different work rates or between the on- and off-transients. Above an, the response becomes more complex with an early component that typically projects to a value that has a gain similar to that of the < an response, but which is supplemented by the addition of a delayed slow kinetic component. We therefore established a constant target VO2 (VO21) for each subject such that with different imposed work rates the contribution to VO21 from the slow phase varied over a wide range. Work rates were chosen so that VO21 was attained at 2-24 min. Five subjects (aged 21-58 years) cycled at four to five different work rates. VO2 was measured breath-by-breath, at VO21 the work rate was abruptly reduced and the subject recovered by cycling unloaded for 15 min. Unlike the on-transient, for which the slow component shows a long delay, the off-transient was best fitted as two simultaneous exponential components. The slower off-transient component had a small amplitude and long time constant, but did not differ significantly among the various tests. The off-transient kinetics for VO2 therefore was independent of the magnitude of the contribution to the slow phase from the on-transient kinetics.

Carbonic anhydrase inhibition delays plasma lactate appearance with no effect on ventilatory threshold.

The effect of carbonic anhydrase (CA) inhibition with acetazolamide (Acz, 10 mg/kg body wt iv) on exercise performance and the ventilatory (VET) and lactate (LaT) thresholds was studied in seven men during ramp exercise (25 W/min) to exhaustion. Breath-by-breath measurements of gas exchange were obtained. Arterialized venous blood was sampled from a dorsal hand vein and analyzed for plasma pH, PCO(2), and lactate concentration ([La(-)](pl)). VET [expressed as O(2) uptake (VO(2)), ml/min] was determined using the V-slope method. LaT (expressed as VO(2), ml/min) was determined from the work rate (WR) at which [La(-)](pl) increased 1.0 mM above rest levels. Peak WR was higher in control (Con) than in Acz sutdies [339 +/- 14 vs. 315 +/- 14 (SE) W]. Submaximal exercise VO(2) was similar in Acz and Con; the lower VO(2) at exhaustion in Acz than in Con (3.824 +/- 0. 150 vs. 4.283 +/- 0.148 l/min) was appropriate for the lower WR. CO(2) output (VCO(2)) was lower in Acz than in Con at exercise intensities >/=125 W and at exhaustion (4.375 +/- 0.158 vs. 5.235 +/- 0.148 l/min). [La(-)](pl) was lower in Acz than in Con during submaximal exercise >/=150 W and at exhaustion (7.5 +/- 1.1 vs. 11.5 +/- 1.1 mmol/l). VET was similar in Acz and Con (2.483 +/- 0.086 and 2.362 +/- 0.110 l/min, respectively), whereas the LaT occurred at a higher VO(2) in Acz than in Con (2.738 +/- 0.223 vs. 2.190 +/- 0.235 l/min). CA inhibition with Acz is associated with impaired elimination of CO(2) during the non-steady-state condition of ramp exercise. The similarity in VET in Con and Acz suggests that La(-) production is similar between conditions but La(-) appearance in plasma is reduced and/or La(-) uptake by other tissues is enhanced after the Acz treatment.

Muscle metabolism during heavy-intensity exercise after acute acetazolamide administration.

Carbonic anhydrase (CA) inhibition is associated with a lower plasma lactate concentration ([La(-)](pl)), but the mechanism for this association is not known. The effect of CA inhibition on muscle high-energy phosphates [ATP and phosphocreatine (PCr)], lactate ([La(-)](m)), and glycogen was examined in seven men [28 +/- 3 (SE) yr] during cycling exercise under control (Con) and acute CA inhibition with acetazolamide (Acz; 10 mg/kg body wt iv). Subjects performed 6-min step transitions in work rate from 0 W to a work rate corresponding to approximately 50% of the difference between the O(2) uptake at the ventilatory threshold and peak O(2) uptake. Muscle biopsies were taken from the vastus lateralis at rest, at 30 min postinfusion, at end exercise (EE), and at 5 and 30 min postexercise. Arterialized venous blood was sampled from a dorsal hand vein and analyzed for [La(-)](pl). ATP was unchanged from rest values; no difference between Con and Acz was observed. The fall in PCr from rest [72 +/- 3 and 73 +/- 3.6 (SE) mmol/kg dry wt for Con and Acz, respectively] to EE (51 +/- 4 and 46 +/- 5 mmol/kg dry wt for Con and Acz, respectively) was similar in Con and Acz. At EE, glycogen (mmol glucosyl units/kg dry wt) decreased to similar values in Con and Acz (307 +/- 16 and 300 +/- 19, respectively). At EE, no difference was observed in [La(-)](m) between conditions (46 +/- 6 and 43 +/- 5 mmol/kg dry wt for Con and Acz, respectively). EE [La(-)](pl) was higher during Con than during Acz (11.4 +/- 1.0 vs. 8.2 +/- 0.6 mmol/l). The similar [La(-)](m) but lower [La(-)](pl) suggests that the uptake of La(-) by other tissues is enhanced after CA inhibition.

Changes in chemoreflex characteristics following acute carbonic anhydrase inhibition in humans at rest.

The effect of carbonic anhydrase (CA) inhibition with acetazolamide (ACZ, 10 mg kg(-1) I.V.) on the peripheral and central chemosensitivity and breathing pattern was investigated in four women and three men aged 25 +/- 3 years using a modified version of Read's rebreathing technique. Subjects were exposed to dynamic increases in CO2 in hypoxic and hyperoxic backgrounds during control conditions and following acute CA inhibition. All manoeuvres were repeated twice and averaged for data analysis. The central chemoreflex sensitivities, estimated from the slopes of the ventilatory response to CO2 during hyperoxic rebreathing, increased following acute CA inhibition (control vs. ACZ treatment: 1.87 +/- 0.66 vs. 4.07 +/- 1.03 l x min(-1) (mmHg CO2)(-1), P < 0.05). The increased slope was reflected by an increase in the rate of rise of tidal volume and breathing frequency. Furthermore with ACZ, there was a left-ward shift of the ventilation vs. end-tidal PCO2 curve during hyperoxic hypercapnia but not hypoxic hypercapnia. The peripheral chemoreflex sensitivity was isolated by subtracting the hyperoxic slope (central only) from the hypoxic slope (central and peripheral). Following ACZ administration, the peripheral chemosensitivity was blunted (control vs. ACZ treatment: 3.66 +/- 0.92 vs. 1.33 +/- 0.46 l x min(-1) (mmHg CO2)(-1), P < 0.05). In conclusion, acute CA inhibition enhanced the central chemosensitivity to CO2 but diminished the peripheral chemosensitivity.