Biomedical subjects

J M Kowalchuk

Publications and source records attributed to J M Kowalchuk.

At least 19 recordsLinked to original sources

PubMed2007

Effects of hyperventilation on phosphocreatine kinetics and muscle deoxygenation during moderate-intensity plantar flexion exercise.

The effects of controlled voluntary hyperventilation (Hyp) on phosphocreatine (PCr) kinetics and muscle deoxygenation were examined during moderate-intensity plantar flexion exercise. Male subjects (n = 7) performed trials consisting of 20-min rest, 6-min exercise, and 10-min recovery in control [Con; end-tidal Pco(2) (Pet(CO(2))) approximately 33 mmHg] and Hyp (Pet(CO(2)) approximately 17 mmHg) conditions. Phosphorus-31 magnetic resonance and near-infrared spectroscopy were used simultaneously to monitor intramuscular acid-base status, high-energy phosphates, and muscle oxygenation. Resting intracellular hydrogen ion concentration ([H(+)](i)) was lower (P < 0.05) in Hyp [90 nM (SD 3)] than Con [96 nM (SD 4)]; however, at end exercise, [H(+)](i) was greater (P < 0.05) in Hyp [128 nM (SD 19)] than Con [120 nM (SD 17)]. At rest, [PCr] was not different between Con [36 mM (SD 2)] and Hyp [36 mM (SD 1)]. The time constant (tau) of PCr breakdown during transition from rest to exercise was greater (P < 0.05) in Hyp [39 s (SD 22)] than Con [32 s (SD 22)], and the PCr amplitude was greater (P < 0.05) in Hyp [26% (SD 4)] than Con [22% (SD 6)]. The deoxyhemoglobin and/or deoxymyoglobin (HHb) tau was similar between Hyp [13 s (SD 8)] and Con [10 s (SD 3)]; however, the amplitude was increased (P < 0.05) in Hyp [40 arbitrary units (au) (SD 23)] compared with Con [26 au (SD 17)]. In conclusion, our results indicate that Hyp-induced hypocapnia enhanced substrate-level phosphorylation during moderate-intensity exercise. In addition, the increased amplitude of the HHb response suggests a reduced local muscle perfusion in Hyp compared with Con.

Adult↗

PubMed2006

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.

Adult↗

PubMed2005

Cerebral blood flow during orthostasis: role of arterial CO2.

Reductions in end-tidal Pco(2) (Pet(CO(2))) during upright posture have been suggested to be the result of hyperventilation and the cause of decreases in cerebral blood flow (CBF). The goal of this study was to determine whether decreases in Pet(CO(2)) reflected decreases in arterial Pco(2) (Pa(CO(2))) and their relation to increases in alveolar ventilation (Va) and decreases in CBF. Fifteen healthy subjects (10 women and 5 men) were subjected to a 10-min head-up tilt (HUT) protocol. Pa(CO(2)), Va, and cerebral flow velocity (CFV) in the middle and anterior cerebral arteries were examined. In 12 subjects who completed the protocol, reductions in Pet(CO(2)) and Pa(CO(2)) (-1.7 +/- 0.5 and -1.1 +/- 0.4 mmHg, P < 0.05) during minute 1 of HUT were associated with a significant increase in Va (+0.7 +/- 0.3 l/min, P < 0.05). However, further decreases in Pa(CO(2)) (-0.5 +/- 0.5 mmHg, P < 0.05), from minute 1 to the last minute of HUT, occurred even though Va did not change significantly (-0.2 +/- 0.3 l/min, P = not significant). Similarly, CFV in the middle and anterior cerebral arteries decreased (-7 +/- 2 and -8 +/- 2%, P < 0.05) from minute 1 to the last minute of HUT, despite minimal changes in Pa(CO(2)). These data suggest that decreases in Pet(CO(2)) and Pa(CO(2)) during upright posture are not solely due to increased Va but could be due to ventilation-perfusion mismatch or a redistribution of CO(2) stores. Furthermore, the reduction in Pa(CO(2)) did not fully explain the decrease in CFV throughout HUT. These data suggest that factors in addition to a reduction in Pa(CO(2)) play a role in the CBF response to orthostatic stress.

Adult↗

PubMed2005

A test to establish maximum O2 uptake despite no plateau in the O2 uptake response to ramp incremental exercise.

The O2 uptake (Vo2) response to ramp incremental (RI) exercise does not consistently demonstrate plateau-like behavior at the limit of tolerance, and hence the requirements for a maximum Vo2 commonly are not met, despite apparent maximum effort. We sought to determine whether an appended step exercise (SE) test at a work rate greater than that achieved in a preceding ramp test would establish the plateau criterion. Seven healthy male adults performed RI cycle ergometry (20 W/min) to the limit of tolerance, followed by 5-min recovery (20 W) and then an SE test at 105% (RISE-105) of the final work rate (WRpeak) achieved during RI. Five of these subjects also performed an RI test followed by SE at 95% WRpeak (RISE-95). Vo2 was measured breath by breath using a turbine and mass spectrometer. The average of the final 15 s of RI or SE was used to establish respective Vo2 peaks. When Vo2 peak was approached, a constant Vo2 value (e.g., a plateau) was not discernable during any RI or SE component of the tests. Although the WRpeak [mean (SD)] was higher during the SE portion [359 W (SD 31)] than during the RI portion [341 W (SD 29)] of the RISE-105, the peak Vo2 was not different [SE, 4.30 l/min (SD 0.51); RI, 4.33 l/min (SD 0.52); P=0.49; n=7]. Similarly, in the RISE-95 test, WRpeak was 310 W (SD 31) for the SE portion and 326 W (SD 32) for the RI portion, yet the peak Vo2 values were not different [SE, 4.12 l/min (SD 0.53); RI, 4.11 l/min (SD 0.48); P=0.78; n=5]. The lack of notable difference between the Vo2 peaks established at different WRpeak values in our RISE protocols provides the plateau criterion for verification of maximum Vo2 in a single test session, even when the data response profiles do not themselves evidence a plateau.

Adult↗

PubMed2005

NaHCO3-induced alkalosis reduces the phosphocreatine slow component during heavy-intensity forearm exercise.

During heavy-intensity exercise, the mechanisms responsible for the continued slow decline in phosphocreatine concentration ([PCr]) (PCr slow component) have not been established. In this study, we tested the hypothesis that a reduced intracellular acidosis would result in a greater oxidative flux and, consequently, a reduced magnitude of the PCr slow component. Subjects (n = 10) performed isotonic wrist flexion in a control trial and in an induced alkalosis (Alk) trial (0.3g/kg oral dose of NaHCO3, 90 min before testing). Wrist flexion, at a contraction rate of 0.5 Hz, was performed for 9 min at moderate- (75% of onset of acidosis; intracellular pH threshold) and heavy-intensity (125% intracellular pH threshold) exercise. 31P-magnetic resonance spectroscopy was used to measure intracellular [H+], [PCr], [Pi], and [ATP]. The initial recovery data were used to estimate the rate of ATP synthesis and oxidative flux at the end of heavy-intensity exercise. In repeated trials, venous blood sampling was used to measure plasma [H+], [HCO3-], and [Lac-]. Throughout rest and exercise, plasma [H+] was lower (P < 0.05) and [HCO3-] was elevated (P < 0.05) in Alk compared with control. During the final 3 min of heavy-intensity exercise, Alk caused a lower (P < 0.05) intracellular [H+] [246 (SD 117) vs. 291 nmol/l (SD 129)], a greater (P < 0.05) [PCr] [12.7 (SD 7.0) vs. 9.9 mmol/l (SD 6.0)], and a reduced accumulation of [ADP] [0.065 (SD 0.031) vs. 0.098 mmol/l (SD 0.059)]. Oxidative flux was similar (P > 0.05) in the conditions at the end of heavy-intensity exercise. In conclusion, our results are consistent with a reduced intracellular acidosis, causing a decrease in the magnitude of the PCr slow component. The decreased PCr slow component in Alk did not appear to be due to an elevated oxidative flux.

Acid-Base Equilibrium↗

PubMed2003

Effects of dichloroacetate on VO2 and intramuscular 31P metabolite kinetics during high-intensity exercise in humans.

Traditional control theories of muscle O2 consumption are based on an "inertial" feedback system operating through features of the ATP splitting (e.g., [ADP] feedback, where brackets denote concentration). More recently, however, it has been suggested that feedforward mechanisms (with respect to ATP utilization) may play an important role by controlling the rate of substrate provision to the electron transport chain. This has been achieved by activation of the pyruvate dehydrogenase complex via dichloroacetate (DCA) infusion before exercise. To investigate these suggestions, six men performed repeated, high-intensity, constant-load quadriceps exercise in the bore of an magnetic resonance spectrometer with each of prior DCA or saline control intravenous infusions. O2 uptake (Vo2) was measured breath by breath (by use of a turbine and mass spectrometer) simultaneously with intramuscular phosphocreatine (PCr) concentration ([PCr]), [Pi], [ATP], and pH (by 31P-MRS) and arterialized-venous blood sampling. DCA had no effect on the time constant (tau) of either Vo2 increase or PCr breakdown [tauVo2 45.5 +/- 7.9 vs. 44.3 +/- 8.2 s (means +/- SD; control vs. DCA); tauPCr 44.8 +/- 6.6 vs. 46.4 +/- 7.5 s; with 95% confidence intervals averaging < +/-2 s]. DCA, however, resulted in significant (P < 0.05) reductions in 1). end-exercise [lactate] (-1.0 +/- 0.9 mM), intramuscular acidification (pH, +0.08 +/- 0.06 units), and [Pi] (-1.7 +/- 2.1 mM); 2). the amplitude of the fundamental components for [PCr] (-1.9 +/- 1.6 mM) and Vo2 (-0.1 +/- 0.07 l/min, or 8%); and 3). the amplitude of the Vo2 slow component. Thus, although the DCA infusion lessened the buildup of potential fatigue metabolites and reduced both the aerobic and anaerobic components of the energy transfer during exercise, it did not enhance either tauVo2 or tau[PCr], suggesting that feedback, rather than feedforward, control mechanisms dominate during high-intensity exercise.

Adenosine Triphosphate↗

PubMed2002

Dynamics of intramuscular 31P-MRS P(i) peak splitting and the slow components of PCr and O2 uptake during exercise.

The dynamics of pulmonary O(2) uptake (Vo(2)) during the on-transient of high-intensity exercise depart from monoexponentiality as a result of a "slow component" whose mechanisms remain conjectural. Progressive recruitment of glycolytic muscle fibers, with slow O(2) utilization kinetics and low efficiency, has, however, been suggested as a mechanism. The demonstration of high- and low-pH components of the exercising skeletal muscle (31)P magnetic resonance (MR) spectrum [inorganic phosphate (P(i)) peak] at high work rates (thought to be reflective of differences between oxidative and glycolytic muscle fibers) is also consistent with this conjecture. We therefore investigated the dynamics of Vo(2) (using a turbine and mass spectrometry) and intramuscular ATP, phosphocreatine (PCr), and P(i) concentrations and pH, estimated from the (31)P MR spectrum. Eleven healthy men performed prone square-wave high-intensity knee extensor exercise in the bore of a whole body MR spectrometer. A Vo(2) slow component of magnitude 15.9 +/- 6.9% of the phase II amplitude was accompanied by a similar response (11.9 +/- 7.1%) in PCr concentration. Only five subjects demonstrated a discernable splitting of the P(i) peak, however, which began from between 35 and 235 s after exercise onset and continued until cessation. As such, the dynamics of the pH distribution in intramuscular compartments did not consistently reflect the temporal features of the Vo(2) slow component, suggesting that P(i) splitting does not uniquely reflect the activity of oxidative or glycolytic muscle fibers per se.

Adenosine Triphosphate↗

PubMed2002

Dynamic asymmetry of phosphocreatine concentration and O(2) uptake between the on- and off-transients of moderate- and high-intensity exercise in humans.

The on- and off-transient (i.e. phase II) responses of pulmonary oxygen uptake (V(O(2))) to moderate-intensity exercise (i.e. below the lactate threshold, theta;(L)) in humans has been shown to conform to both mono-exponentiality and 'on-off' symmetry, consistent with a system manifesting linear control dynamics. However above theta;(L) the V(O(2)) kinetics have been shown to be more complex: during high-intensity exercise neither mono-exponentiality nor 'on-off' symmetry have been shown to appropriately characterise the V(O(2)) response. Muscle [phosphocreatine] ([PCr]) responses to exercise, however, have been proposed to be dynamically linear with respect to work rate, and to demonstrate 'on-off' symmetry at all work intenisties. We were therefore interested in examining the kinetic characteristics of the V(O(2)) and [PCr] responses to moderate- and high-intensity knee-extensor exercise in order to improve our understanding of the factors involved in the putative phosphate-linked control of muscle oxygen consumption. We estimated the dynamics of intramuscular [PCr] simultaneously with those of V(O(2)) in nine healthy males who performed repeated bouts of both moderate- and high-intensity square-wave, knee-extension exercise for 6 min, inside a whole-body magnetic resonance spectroscopy (MRS) system. A transmit-receive surface coil placed under the right quadriceps muscle allowed estimation of intramuscular [PCr]; V(O(2)) was measured breath-by-breath using a custom-designed turbine and a mass spectrometer system. For moderate exercise, the kinetics were well described by a simple mono-exponential function (following a short cardiodynamic phase for V(O(2))), with time constants (tau) averaging: tauV(O(2))(,on) 35 +/- 14 s (+/- S.D.), tau[PCr](on) 33 +/- 12 s, tauV(O(2))(,off) 50 +/- 13 s and tau[PCr](off) 51 +/- 13 s. The kinetics for both V(O(2)) and [PCr] were more complex for high-intensity exercise. The fundamental phase expressing average tau values of tauV(O(2))(,on) 39 +/- 4 s, tau[PCr](on) 38 +/- 11 s, tauV(O(2))(,off) 51 +/- 6 s and tau[PCr](off) 47 +/- 11 s. An associated slow component was expressed in the on-transient only for both V(O(2)) and [PCr], and averaged 15.3 +/- 5.4 and 13.9 +/- 9.1 % of the fundamental amplitudes for V(O(2)) and [PCr], respectively. In conclusion, the tau values of the fundamental component of [PCr] and V(O(2)) dynamics cohere to within 10 %, during both the on- and off-transients to a constant-load work rate of both moderate- and high-intensity exercise. On average, approximately 90 % of the magnitude of the V(O(2)) slow component during high-intensity exercise is reflected within the exercising muscle by its [PCr] response.

Adult↗

PubMed2001

Effects of prior exercise on oxygen uptake and phosphocreatine kinetics during high-intensity knee-extension exercise in humans.

1. A prior bout of high-intensity square-wave exercise can increase the temporal adaptation of pulmonary oxygen uptake (.V(O2)) to a subsequent bout of high-intensity exercise. The mechanisms controlling this adaptation, however, are poorly understood. 2. We therefore determined the dynamics of intramuscular [phosphocreatine] ([PCr]) simultaneously with those of .V(O2) in seven males who performed two consecutive bouts of high-intensity square-wave, knee-extensor exercise in the prone position for 6 min with a 6 min rest interval. A magnetic resonance spectroscopy (MRS) transmit-receive surface coil under the quadriceps muscle allowed estimation of [PCr]; .V(O2) was measured breath-by-breath using a custom-designed turbine and a mass spectrometer system. 3. The .V(O2) kinetics of the second exercise bout were altered compared with the first such that (a) not only was the instantaneous rate of .V(O2) change (at a given level of .V(O2)) greater but the phase II tau was also reduced - averaging 46.6 +/- 6.0 s (bout 1) and 40.7 +/- 8.4 s (bout 2) (mean +/- S.D.) and (b) the magnitude of the later slow component was reduced. 4. This was associated with a reduction of, on average, 16.1% in the total exercise-induced [PCr] decrement over the 6 min of the exercise, of which 4.0% was due to a reduction in the slow component of [PCr]. There was no discernable alteration in the initial rate of [PCr] change. The prior exercise, therefore, changed the multi-compartment behaviour towards that of functionally first-order dynamics. 5. These observations demonstrate that the .V(O2) responses relative to the work rate input for high-intensity exercise are non-linear, as are, it appears, the putative phosphate-linked controllers for which [PCr] serves as a surrogate.

Adult↗

PubMed2001

Effect of prior metabolic rate on the kinetics of oxygen uptake during moderate-intensity exercise.

Pulmonary oxygen uptake (VO2) dynamics during moderate-intensity exercise are often assumed to be dynamically linear (i.e. neither the gain nor the time constant (tau) of the response varies as a function of work rate). However, faster, slower and unchanged VO2 kinetics have been reported during work-to-work transitions compared to rest-to-work transitions, all within the moderate-intensity domain. In an attempt to resolve these discrepancies and to improve the confidence of the parameter estimation, we determined the VO2 response dynamics using the averaged response to repeated exercise bouts in seven healthy male volunteers. Each subject initially performed a ramp-incremental exercise test for the estimation of the lactate threshold (thetaL). They then performed an average of four repetitions of each of three constant-work-rate (WR) tests: (1) between 20 W and a work rate of 50% (WR50) between 20 W and 90% thetaL (step 1-->2), (2) between WR50 and 90% thetaL (step 2-->3), and (3) between 20 W and 90% thetaL (step 1-->3); 6 min was spent at each work rate increment and decrement. Parameters of the kinetic response of phase II VO2 were established by non-linear least-squares fitting techniques. The kinetics of VO2 were significantly slower at the upper reaches of the moderate-intensity domain (step 2-->3) compared to steps 1-->2 and 1-->3 [group mean (SD) phase II tau: step 1-->2 25.3 (4.9) s, step 2-->3 40.0 (7.4) s and step 1-->3 32.2 (6.9) s]. The off-transient values of tau were not significantly different from each other: 36.8 (16.3) s, 38.9 (11.6) s and 30.8 (5.7) s for steps 1-->2, 2-->3 and 1-->3, respectively. Surprisingly, the on-transient gain (G, deltaVO2/deltaWR) was also found to vary among the three steps [G = 10.56 (0.42) ml x min(-1) W(-1) 11.85 (0.64) ml x min(-1) W(-1) and 11.23 (0.52) ml x min(-1) W(-1) for steps 1-->2, 2-->3 and 1-->3, respectively]; the off-transient G did not vary significantly and was close to that for the on-transient step 1-->3 in all cases. Our results do not support a dynamically linear system model of VO2 during cycle ergometer exercise even in the moderate-intensity domain. The greater oxygen deficit per unit power increment in the higher reaches of the moderate-intensity domain necessitates a greater transient lactate contribution to the energy transfer, or a greater phosphocreatine breakdown, or possibly both.

Adult↗

PubMed2001

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.

Adult↗

PubMed2001

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.

Aged↗

PubMed2000

Intersample fluctuations in phosphocreatine concentration determined by 31P-magnetic resonance spectroscopy and parameter estimation of metabolic responses to exercise in humans.

The ATP turnover rate during constant-load exercise is often estimated from the initial rate of change of phosphocreatine concentration ([PCr]) using 31P-magnetic resonance spectroscopy (MRS). However, the phase and amplitude characteristics of the sample-to-sample fluctuations can markedly influence this estimation (as well as that for the time constant (tau) of the [PCr] change) and confound its physiological interpretation especially for small amplitude responses. This influence was investigated in six healthy males who performed repeated constant-load quadriceps exercise of a moderate intensity in a whole-body MRS system. A transmit- receive surface coil was placed under the right quadriceps, allowing determination of intramuscular [PCr]; pulmonary oxygen uptake (VO2) was simultaneously determined, breath-by-breath, using a mass spectrometer and a turbine volume measuring module. The probability density functions (PDF) of [PCr] and VO2 fluctuations were determined for each test during the steady states of rest and exercise and the PDF was then fitted to a Gaussian function. The standard deviation of the [PCr] and VO2 fluctuations at rest and during exercise (sr and sw, respectively) and the peak centres of the distributions (xc(r) and xc(w)) were determined, as were the skewness (gamma1) and kurtosis (gamma2) coefficients. There was no difference between sr and sw for [PCr] relative to the resting control baseline (s(r) = 1.554 %delta (s.d. = 0.44), s(w) = 1.514 %delta (s.d. = 0.35)) or the PDF peak centres (xc(r) = -0.013 %delta (s.d. = 0.09), xc(w) -0.197 %delta (s.d. = 0.18)). The standard deviation and peak centre of the 'noise' in VO2 also did not vary between rest and exercise (sr = 0.0427 l min(-1) (s.d. = 0.0104), s(w) = 0.0640 l min(-1) (s.d. = 0.0292); xc(r) = -0.0051 l min(-1) (s.d. = 0.0069), xc(w) 0.0022 l min(-1) (s.d. = 0.0034)). Our results demonstrate that the intersample 'noise' associated with [PCr] determination by 31P-MRS may be characterised as a stochastic Gaussian process that is uncorrelated with work rate, as previously described for VO2. This 'noise' can significantly affect the estimation of tau[PCr] and especially the initial rate of change of [PCr], i.e. the fluctuations can lead to variations in estimation of the initial rate of change of [PCr] of more than twofold, if the inherent 'noise' is not accounted for. This 'error' may be significantly reduced in such cases if the initial rate of change is estimated from the time constant and amplitude of the response.

Adenosine Triphosphate↗

PubMed2000

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.

Acetazolamide↗

PubMed2000

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.

Acetazolamide↗

PubMed2000

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.

Acetazolamide↗

PubMed2000

Body position and cardiac dynamic and chronotropic responses to steady-state isocapnic hypoxaemia in humans.

Neural mediation of the human cardiac response to isocapnic (IC) steady-state hypoxaemia was investigated using coarse-graining spectral analysis of heart rate variability (HRV). Six young adults were exposed in random order to a hypoxia or control protocol, in supine and sitting postures, while end-tidal PCO2 (PET,CO2) was clamped at resting eucapnic levels. An initial 11 min period of euoxia (PET,O2 100 mmHg; 13.3 kPa) was followed by a 22 min exposure to hypoxia (PET,O2 55 mmHg; 7.3 kPa), or continued euoxia (control). Harmonic and fractal powers of HRV were determined for the terminal 400 heart beats in each time period. Ventilation was stimulated (P < 0.05) and cardiac dynamics altered only by exposure to hypoxia. The cardiac interpulse interval was shortened (P < 0.001) similarly during hypoxia in both body positions. Vagally mediated high-frequency harmonic power (Ph) of HRV was decreased by hypoxia only in the supine position, while the fractal dimension, also linked to cardiac vagal control, was decreased in the sitting position (P < 0.05). However, low-frequency harmonic power (Pl) and the HRV indicator of sympathetic activity (Pl/Ph) were not altered by hypoxia in either position. These results suggest that, in humans, tachycardia induced by moderate IC hypoxaemia (arterial O2 saturation Sa,O2 85 %) was mediated by vagal withdrawal, irrespective of body position and resting autonomic balance, while associated changes in HRV were positionally dependent.

Adult↗

PubMed2000

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.

Acetazolamide↗