31-P NMR characterization of the metabolic anomalies associated with the lack of glycogen phosphorylase activity in human forearm muscle.

Exercise-induced changes in phosphorus-containing metabolites and intracellular pH (pHi) have been studied in the finger flexor muscles of 3 patients with glycogen phosphorylase deficiency (McArdle's disease) in comparison to 14 healthy volunteers. At rest, no difference was observed for PCr/Pi ratio and pHi while patients exhibited a higher PCr/ATP ratio (5.91 +/- 0.98 vs 4.02 +/- 0.6). At end-of-exercise, PCr/Pi was abnormally low (0.51 +/- 0.19 vs 1.64 +/- 0.37) whereas no acidosis was observed. The slow recovery of PCr/Pi ratio indicates an impairment of oxidative capacity accompanying the defect in the glycogenolytic pathway. The failure to observe a transient Pi disappearance at the onset of recovery (an index of glycogen phosphorylase activity) can be used in conjunction with the lack of exercise acidosis as a diagnostic index of McArdle's disease.     

Metabolic effects of induced alkalosis during progressive forearm exercise to fatigue.

Metabolic alkalosis induced by sodium bicarbonate (NaHCO(3)) ingestion has been shown to enhance performance during brief high-intensity exercise. The mechanisms associated with this increase in performance may include increased muscle phosphocreatine (PCr) breakdown, muscle glycogen utilization, and plasma lactate (Lac(-)(pl)) accumulation. Together, these changes would imply a shift toward a greater contribution of anaerobic energy production, but this statement has been subject to debate. In the present study, subjects (n = 6) performed a progressive wrist flexion exercise to volitional fatigue (0.5 Hz, 14-21 min) in a control condition (Con) and after an oral dose of NaHCO(3) (Alk: 0.3 g/kg; 1.5 h before testing) to evaluate muscle metabolism over a complete range of exercise intensities. Phosphorus-31 magnetic resonance spectroscopy was used to continuously monitor intracellular pH, [PCr], [P(i)], and [ATP] (brackets denote concentration). Blood samples drawn from a deep arm vein were analyzed with a blood gas-electrolyte analyzer to measure plasma pH, Pco(2), and [Lac(-)](pl), and plasma [HCO(3)(-)] was calculated from pH and Pco(2). NaHCO(3) ingestion resulted in an increased (P < 0.05) plasma pH and [HCO(3)(-)] throughout rest and exercise. Time to fatigue and peak power output were increased (P < 0.05) by approximately 12% in Alk. During exercise, a delayed (P < 0.05) onset of intracellular acidosis (1.17 +/- 0.26 vs. 1.28 +/- 0.22 W, Con vs. Alk) and a delayed (P < 0.05) onset of rapid increases in the [P(i)]-to-[PCr] ratio (1.21 +/- 0.30 vs. 1.30 +/- 0.30 W) were observed in Alk. No differences in total [H(+)], [P(i)], or [Lac(-)](pl) accumulation were detected. In conclusion, NaHCO(3) ingestion was shown to increase plasma pH at rest, which resulted in a delayed onset of intracellular acidification during incremental exercise. Conversely, NaHCO(3) was not associated with increased [Lac(-)](pl) accumulation or PCr breakdown.     

Muscle metabolic responses to exercise above and below the "critical power" assessed using 31P-MRS

We tested the hypothesis that the asymptote of the hyperbolic relationship between work rate and time to exhaustion during muscular exercise, the "critical power" (CP), represents the highest constant work rate that can be sustained without a progressive loss of homeostasis [as assessed using (31)P magnetic resonance spectroscopy (MRS) measurements of muscle metabolites]. Six healthy male subjects initially completed single-leg knee-extension exercise at three to four different constant work rates to the limit of tolerance (range 3-18 min) for estimation of the CP (mean +/- SD, 20 +/- 2 W). Subsequently, the subjects exercised at work rates 10% below CP (CP) for as long as possible, while the metabolic responses in the contracting quadriceps muscle, i.e., phosphorylcreatine concentration ([PCr]), P(i) concentration ([P(i)]), and pH, were estimated using (31)P-MRS. All subjects completed 20 min of CP exercise was 14.7 +/- 7.1 min. During CP exercise, however, [PCr] continued to fall to the point of exhaustion and [P(i)] and pH changed precipitously to values that are typically observed at the termination of high-intensity exhaustive exercise (end-exercise values = 26 +/- 16% of baseline [PCr], 564 +/- 167% of baseline [P(i)], and pH 6.87 +/- 0.10, all P < 0.05 vs. 相似文献   

A simplified two-component model of blood pressure fluctuation

We propose a simple moving-average (MA) model that uses the low-frequency (LF) component of the peroneal muscle sympathetic nerve spike rate (LF(spike rate)) and the high-frequency (HF) component of respiration (HF(Resp)) to describe the LF neurovascular fluctuations and the HF mechanical oscillations in systolic blood pressure (SBP), respectively. This method was validated by data from eight healthy subjects (23-47 yr old, 6 male, 2 female) during a graded tilt (15 degrees increments every 5 min to a 60 degrees angle). The LF component of SBP (LF(SBP)) had a strong baroreflex-mediated feedback correlation with LF(spike rate) (r = -0.69 +/- 0.05) and also a strong feedforward relation to LF(spike rate) [r = 0.58 +/- 0.03 with LF(SBP) delay (tau) = 5.625 +/- 0.15 s]. The HF components of spike rate (HF(spike rate)) and SBP (HF(SBP)) were not significantly correlated. Conversely, HF(Resp) and HF(SBP) were highly correlated (r = -0.79 +/- 0.04), whereas LF(Resp) and LF(SBP) were significantly less correlated (r = 0.45 +/- 0.08). The mean correlation coefficients between the measured and model-predicted LF(SBP) (r = 0.74 +/- 0.03) in the supine position did not change significantly during tilt. The mean correlation between the measured and model-predicted HF(SBP) was 0.89 +/- 0.02 in the supine position. R(2) values for the regression analysis of the model-predicted and measured LF and HF powers indicate that 78 and 91% of the variability in power can be explained by the linear relation of LF(spike rate) to LF(SBP) and HF(Resp) to HF(SBP). We report a simple two-component model using neural sympathetic and mechanical respiratory inputs that can explain the majority of blood pressure fluctuation at rest and during orthostatic stress in healthy subjects.     

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.     

Influence of phosphagen concentration on phosphocreatine breakdown kinetics. Data from human gastrocnemius muscle

At the onset of a square-wave exercise of moderate intensity, in the absence of any detectable lactate production, the hydrolysis of phosphocreatine (PCr) fills the gap between energy requirement and energy yield by oxidative pathways, thus representing a readily available source of energy for the muscle. We verified experimentally the relationships between high-energy phosphates and/or their changes and the time constant of PCr concentration ([PCr]) kinetics in humans (tau(PCr)). High-energy phosphate concentration (by (31)P-NMR spectroscopy) in the calf muscles were measured during three repetitions of the rest-to-work transition of moderate aerobic square-wave exercise on nine healthy volunteers, while resting [PCr] was estimated from the appropriate spectroscopy data. PCr concentration decreased significantly (22 +/- 6%) from rest to steady-state exercise, without differences among the three repetitions. Absolute resting [PCr] and tau(PCr) were consistent with literature values, amounting to 27.5 +/- 2.2 mM and 23.9 +/- 2.9 s, respectively. No significant relationships were detected between individual tau(PCr) and mechanical power, fraction or absolute amount of PCr hydrolyzed, or change in ADP concentration. On the contrary, individual tau(PCr) (s) was linearly related to absolute resting [PCr] (mM), the relationship being described by: tau(PCr) = 0.656 + 0.841.[PCr] (n = 9, R = 0.708, P < 0.05). These data support the view that in humans PCr concentration sets the time course of the oxidative metabolism in skeletal muscle at the start of exercise, being one of the main controllers of oxidative phosphorylation.     

Intracellular PO2 kinetics at different contraction frequencies in Xenopus single skeletal muscle fibers.

Increasing contraction frequency in single skeletal muscle fibers has been shown to increase the magnitude of the fall in intracellular Po(2) (Pi(O(2))), reflecting a greater metabolic rate. To test whether Pi(O(2)) kinetics are altered by contraction frequency through this increase in metabolic stress, Pi(O(2)) was measured in Xenopus single fibers (n = 11) during and after contraction bouts at three different frequencies. Pi(O(2)) was measured via phosphorescence quenching at 0.16-, 0.25-, and 0.5-Hz tetanic stimulation. The kinetics of the change in Pi(O(2)) from resting baseline to end-contraction values and end contraction to rest were described as a mean response time (MRT) representing the time to 63% of the change in Pi(O(2)). As predicted, the fall in Pi(O(2)) from baseline following contractions was progressively greater at 0.5 and 0.25 Hz than at 0.16 Hz (32.8 +/- 2.1 and 29.3 +/- 2.0 Torr vs. 23.6 +/- 2.2 Torr, respectively) since metabolic demand was greater. The MRT for the decrease in Pi(O(2)) was progressively faster at the higher frequencies (0.5 Hz: 45.3 +/- 4.5 s; 0.25 Hz: 63.3 +/- 4.1 s; 0.16 Hz: 78.0 +/- 4.1 s), suggesting faster accumulation of stimulators of oxidative phosphorylation. The MRT for Pi(O(2)) off-kinetics (0.5 Hz: 84.0 +/- 11.7 s; 0.25 Hz: 79.1 +/- 8.4 s; 0.16 Hz: 81.1 +/- 8.3 s) was not different between trials. These data demonstrate in single fibers that the rate of the fall in Pi(O(2)) is dependent on contraction frequency, whereas the rate of recovery following contractions is independent of either the magnitude of the fall in Pi(O(2)) from baseline or the contraction frequency. This suggests that stimulation frequency plays an integral role in setting the initial metabolic response to work in isolated muscle fibers, possibly due to temporal recovery between contractions, but it does not determine recovery kinetics.     

Frequency-dependent baroreflex modulation of blood pressure and heart rate variability in conscious mice

The goal of this study was to determine the baroreflex influence on systolic arterial pressure (SAP) and pulse interval (PI) variability in conscious mice. SAP and PI were measured in C57Bl/6J mice subjected to sinoaortic deafferentation (SAD, n = 21) or sham surgery (n = 20). Average SAP and PI did not differ in SAD or control mice. In contrast, SAP variance was enhanced (21 +/- 4 vs. 9.5 +/- 1 mmHg2) and PI variance reduced (8.8 +/- 2 vs. 26 +/- 6 ms2) in SAD vs. control mice. High-frequency (HF: 1-5 Hz) SAP variability quantified by spectral analysis was greater in SAD (8.5 +/- 2.0 mmHg2) compared with control (2.5 +/- 0.2 mmHg2) mice, whereas low-frequency (LF: 0.1-1 Hz) SAP variability did not differ between the groups. Conversely, LF PI variability was markedly reduced in SAD mice (0.5 +/- 0.1 vs. 10.8 +/- 3.4 ms2). LF oscillations in SAP and PI were coherent in control mice (coherence = 0.68 +/- 0.05), with changes in SAP leading changes in PI (phase = -1.41 +/- 0.06 radians), but were not coherent in SAD mice (coherence = 0.08 +/- 0.03). Blockade of parasympathetic drive with atropine decreased average PI, PI variance, and LF and HF PI variability in control (n = 10) but had no effect in SAD (n = 6) mice. In control mice, blockade of sympathetic cardiac receptors with propranolol increased average PI and decreased PI variance and LF PI variability (n = 6). In SAD mice, propranolol increased average PI (n = 6). In conclusion, baroreflex modulation of PI contributes to LF, but not HF PI variability, and is mediated by both sympathetic and parasympathetic drives in conscious mice.     

Does nitric oxide buffer arterial blood pressure variability in humans?

Animal studies suggest that nitric oxide (NO) plays an important role in buffering short-term arterial pressure variability, but data from humans addressing this hypothesis are scarce. We evaluated the effects of NO synthase (NOS) inhibition on arterial blood pressure (BP) variability in eight healthy subjects in the supine position and during 60 degrees head-up tilt (HUT). Systemic NOS was blocked by intravenous infusion of N(G)-monomethyl-L-arginine (L-NMMA). Electrocardiogram and beat-by-beat BP in the finger (Finapres) were recorded continuously for 6 min, and brachial cuff BP was recorded before and after L-NMMA in each body position. BP and R-R variability and their transfer functions were quantified by power spectral analysis in the low-frequency (LF; 0.05-0.15 Hz) and high-frequency (HF; 0.15-0.35 Hz) ranges. L-NMMA infusion increased supine BP (systolic, 109 +/- 4 vs. 122 +/- 3 mmHg, P = 0.03; diastolic, 68 +/- 2 vs. 78 +/- 3 mmHg, P = 0.002), but it did not affect supine R-R interval or BP variability. Before L-NMMA, HUT decreased HF R-R variability (P = 0.03), decreased transfer function gain (LF, 12 +/- 2 vs. 5 +/- 1 ms/mmHg, P = 0.007; HF, 18 +/- 3 vs. 3 +/- 1 ms/mmHg, P = 0.002), and increased LF BP variability (P < 0.0001). After L-NMMA, HUT resulted in similar changes in BP and R-R variability compared with tilt without L-NMMA. Increased supine BP after L-NMMA with no effect on BP variability during HUT suggests that tonic release of NO is important for systemic vascular tone and thus steady-state arterial pressure, but NO does not buffer dynamic BP oscillations in humans.     

ATP synthesis and proton handling in muscle during short periods of exercise and subsequent recovery.

We used (31)P-magnetic resonance spectroscopy to study proton buffering in finger flexor muscles of eight healthy men (25-45 yr), during brief (18-s) voluntary finger flexion exercise (0.67-Hz contraction at 10% maximum voluntary contraction; 50/50 duty cycle) and 180-s recovery. Phosphocreatine (PCr) concentration fell 19 +/- 2% during exercise and then recovered with half time = 0.24 +/- 0.01 min. Cell pH rose by 0.058 +/- 0.003 units during exercise as a result of H(+) consumption by PCr splitting, which (assuming no lactate production or H(+) efflux) implies a plausible non-P(i) buffer capacity of 20 +/- 3 mmol. l intracellular water(-1). pH unit(-1). There was thus no evidence of significant glycogenolysis to lactate during exercise. Analysis of PCr kinetics as a classic linear response suggests that oxidative ATP synthesis reached 48 +/- 2% of ATP demand by the end of exercise; the rest was met by PCr splitting. Postexercise pH recovery was faster than predicted, suggesting "excess proton" production, with a peak value of 0.6 +/- 0.2 mmol/l intracellular water at 0.45 min of recovery, which might be due to, e.g., proton influx driven by cellular alkalinization, or a small glycolytic contribution to PCr resynthesis in recovery.     

Use of phosphocreatine kinetics to determine the influence of creatine on muscle mitochondrial respiration: an in vivo 31P-MRS study of oral creatine ingestion.

Recent human isolated muscle fiber studies suggest that phosphocreatine (PCr) and creatine (Cr) concentrations play a role in the regulation of mitochondrial respiration rate. To determine whether similar regulatory mechanisms are present in vivo, this study examined the relationship between skeletal muscle mitochondrial respiration rate and end-exercise PCr, Cr, PCr-to-Cr ratio (PCr/Cr), ADP, and pH by using (31)P-magnetic resonance spectroscopy in 16 men and women (36.9 +/- 4.6 yr). The initial PCr resynthesis rate and time constant (T(c)) were used as indicators of mitochondrial respiration after brief (10-12 s) and exhaustive (1-4 min) dynamic knee extension exercise performed in placebo and creatine-supplemented conditions. The results show that the initial PCr resynthesis rate has a strong relationship with end-exercise PCr, Cr, and PCr/Cr (r > 0.80, P < 0.001), a moderate relationship with end-exercise ADP (r = 0.77, P < 0.001), and no relationship with end-exercise pH (r = -0.14, P = 0.34). The PCr T(c) was not as strongly related to PCr, Cr, PCr/Cr, and ADP (r < 0.77, P < 0.001-0.18) and was significantly influenced by end-exercise pH (r = -0.43, P < 0.01). These findings suggest that end-exercise PCr and Cr should be taken into consideration when PCr recovery kinetics is used as an indicator of mitochondrial respiration and that the initial PCr resynthesis rate is a more reliable indicator of mitochondrial respiration compared with the PCr T(c).     

Skeletal muscle phosphocreatine recovery in exercise-trained humans is dependent on O2 availability.

In skeletal muscle, phosphocreatine (PCr) recovery from submaximal exercise has become a reliable and accepted measure of muscle oxidative capacity. During exercise, O2 availability plays a role in determining maximal oxidative metabolism, but the relationship between O2 availability and oxidative metabolism measured by 31P-magnetic resonance spectroscopy (MRS) during recovery from exercise has never been studied. We used 31P-MRS to study exercising human gastrocnemius muscle under conditions of varied fractions of inspired O2 (FIO2) to test the hypothesis that varied O2 availability modulates PCr recovery from submaximal exercise. Six male subjects performed three bouts of 5-min steady-state submaximal plantar flexion exercise followed by 5 min of recovery in a 1.5-T magnet while breathing three different FIO2 concentrations (0.10, 0. 21, and 1.00). Under each FIO2 treatment, the PCr recovery time constants were significantly different, being longer in hypoxia [33. 5 +/- 4.1 s (SE)] and shorter in hyperoxia (20.0 +/- 1.8 s) than in normoxia (25.0 +/- 2.7 s) (P 相似文献   

Regulation of middle cerebral artery blood velocity during dynamic exercise in humans: influence of aging.

Although cerebral autoregulation (CA) appears well maintained during mild to moderate intensity dynamic exercise in young subjects, it is presently unclear how aging influences the regulation of cerebral blood flow during physical activity. Therefore, to address this question, middle cerebral artery blood velocity (MCAV), mean arterial pressure (MAP), and the partial pressure of arterial carbon dioxide (Pa(CO(2))) were assessed at rest and during steady-state cycling at 30% and 50% heart rate reserve (HRR) in 9 young (24 +/- 3 yr; mean +/- SD) and 10 older middle-aged (57 +/- 7 yr) subjects. Transfer function analysis between changes in MAP and mean MCAV (MCAV(mean)) in the low-frequency (LF) range were used to assess dynamic CA. No age-group differences were found in Pa(CO(2)) at rest or during cycling. Exercise-induced increases in MAP were greater in older subjects, while changes in MCAV(mean) were similar between groups. The cerebral vascular conductance index (MCAV(mean)/MAP) was not different at rest (young 0.66 +/- 0.04 cm x s(-1) x mmHg(-1) vs. older 0.67 +/- 0.03 cm x s(-1) x mmHg(-1); mean +/- SE) or during 30% HRR cycling between groups but was reduced in older subjects during 50% HRR cycling (young 0.67 +/- 0.03 cm x s(-1) x mmHg(-1) vs. older 0.56 +/- 0.02 cm x s(-1) x mmHg(-1); P < 0.05). LF transfer function gain and phase between MAP and MCAV(mean) was not different between groups at rest (LF gain: young 0.95 +/- 0.05 cm x s(-1) x mmHg(-1) vs. older 0.88 +/- 0.06 cm x s(-1) x mmHg(-1); P > 0.05) or during exercise (LF gain: young 0.80 +/- 0.05 cm x s(-1) x mmHg(-1) vs. older 0.72 +/- 0.07 cm x s(-1) x mmHg(-1) at 50% HRR; P > 0.05). We conclude that despite greater increases in MAP, the regulation of MCAV(mean) is well maintained during dynamic exercise in healthy older middle-aged subjects.     

Human skeletal muscle exercise metabolism following an expedition to mount denali

Chronic exposure to high altitude is known to result in changes in the mechanisms regulating O(2) delivery to the contracting muscle. However, the effects of acclimatization on metabolism in the contracting muscle cell remain unclear. In this study, we have investigated the hypothesis that acclimatization would result in a closer coupling between ATP utilization and ATP production and that the improved energy state would be accompanied by a reorganization of the metabolic pathways consisting of an increased oxidative and decreased glycolytic potential. Five men, mean age of 28 +/- 2 (SE) yr, performed a standardized, two-stage submaximal cycling task in normoxia for 20 min at each of 59 and 74% peak O(2) consumption before and 3-4 days after returning from a 21-day expedition to Mount Denali (6,194 m). Acclimatization was without effect in altering the resting values of the adenine nucleotides (ATP, ADP, AMP), inosine monophosphate (IMP), or phosphocreatine (PCr) in the vastus lateralis. During exercise (40 min) after acclimatization compared with preacclimatization, PCr was not as depressed (33.2 +/- 7.1 vs. 40.6 +/- 5.4 mmol/kg dry wt) and IMP (0.289 +/- 0.11 vs. 0. 131 +/- 0.03 mmol/kg dry wt) and lactate (26.1 +/- 6.2 vs. 18.6 +/- 8.8 mmol/kg dry wt) in contracting muscle were not as elevated (P < 0.05). Although no effect of acclimatization was observed for the maximal activity (mol. kg protein(-1). h(-1)) of citrate synthase (4. 76 +/- 0.44 vs. 4.94 +/- 0.45), lactate dehydrogenase was increased by 13% (36.5 +/- 2.6 vs. 41.2 +/- 3.1, P < 0.05). It is concluded that acclimatization results in an improved energy state in the contracting muscle when tested under normoxic conditions; however, these effects are not associated with a higher oxidative potential or a lower glycolytic potential as hypothesized.     

Creatine reduces human muscle PCr and pH decrements and P(i) accumulation during low-intensity exercise.

The purpose of this study was to examine with (31)P-magnetic resonance spectroscopy energy metabolism during repeated plantar flexion isometric exercise (Ex-1-Ex-4) at 32 +/- 1 and 79 +/- 4% of maximal voluntary contraction (MVC) before and during a creatine (Cr) feeding period of 5 g/day for 11 days. Eight trained male subjects participated in the study. ATP was unchanged with Cr supplementation at rest and during exercise at both intensities. Resting muscle phosphocreatine (PCr) increased (P < 0.05) from 18.3 +/- 0.9 (before) to 19.6 +/- 1.0 mmol/kg wet wt after 9 days. At 79% MVC, PCr used, P(i) accumulated, and pH at the end of Ex-1-Ex-4 were similar after 4 and 11 days of Cr supplementation. In contrast, PCr utilization and P(i) accumulation were lower and pH was higher for exercise at 32% MVC with Cr supplementation, suggesting aerobic resynthesis of PCr was more rapid during exercise. These results suggest that elevating muscle Cr enhances oxidative phosphorylation during mild isometric exercise, where it is expected that oxygen delivery matches demands and predominantly slow-twitch motor units are recruited.     

Influence of endurance training on muscle [PCr] kinetics during high-intensity exercise

We hypothesized that a period of endurance training would result in a speeding of muscle phosphocreatine concentration ([PCr]) kinetics over the fundamental phase of the response and a reduction in the amplitude of the [PCr] slow component during high-intensity exercise. Six male subjects (age 26 +/- 5 yr) completed 5 wk of single-legged knee-extension exercise training with the alternate leg serving as a control. Before and after the intervention period, the subjects completed incremental and high-intensity step exercise tests of 6-min duration with both legs separately inside the bore of a whole-body magnetic resonance spectrometer. The time-to-exhaustion during incremental exercise was not changed in the control leg [preintervention group (PRE): 19.4 +/- 2.3 min vs. postintervention group (POST): 19.4 +/- 1.9 min] but was significantly increased in the trained leg (PRE: 19.6 +/- 1.6 min vs. POST: 22.0 +/- 2.2 min; P < 0.05). During step exercise, there were no significant changes in the control leg, but end-exercise pH and [PCr] were higher after vs. before training. The time constant for the [PCr] kinetics over the fundamental exponential region of the response was not significantly altered in either the control leg (PRE: 40 +/- 13 s vs. POST: 43 +/- 10 s) or the trained leg (PRE: 38 +/- 8 s vs. POST: 40 +/- 12 s). However, the amplitude of the [PCr] slow component was significantly reduced in the trained leg (PRE: 15 +/- 7 vs. POST: 7 +/- 7% change in [PCr]; P < 0.05) with there being no change in the control leg (PRE: 13 +/- 8 vs. POST: 12 +/- 10% change in [PCr]). The attenuation of the [PCr] slow component might be mechanistically linked with enhanced exercise tolerance following endurance training.     

Skeletal muscle oxidative metabolism in sedentary humans: 31P-MRS assessment of O2 supply and demand limitations.

Previously, it was demonstrated in exercise-trained humans that phosphocreatine (PCr) recovery is significantly altered by fraction of inspired O2 (FI(O2)), suggesting that in this population under normoxic conditions, O2 availability limits maximal oxidative rate. Haseler LJ, Hogan ML, and Richardson RS. J Appl Physiol 86: 2013-2018, 1999. To further elucidate these population-specific limitations to metabolic rate, we used 31P-magnetic resonance spectroscopy to study the exercising human gastrocnemius muscle under conditions of varied FI(O2) in sedentary subjects. To test the hypothesis that PCr recovery from submaximal exercise in sedentary subjects is not limited by O2 availability, but rather by their mitochondrial capacity, six sedentary subjects performed three bouts of 6-min steady-state submaximal plantar flexion exercise followed by 5 min of recovery while breathing three different FI(O2) (0.10, 0.21, and 1.00). PCr recovery time constants were significantly longer in hypoxia (47.0 +/- 3.2 s), but there was no difference between hyperoxia (31.8 +/- 1.9 s) and normoxia (30.0 +/- 2.1 s) (mean +/- SE). End-exercise pH was not significantly different across treatments. These results suggest that the maximal muscle oxidative rate of these sedentary subjects, unlike their exercise-trained counterparts, is limited by mitochondrial capacity and not O2 availability in normoxia. Additionally, the significant elongation of PCr recovery in these subjects in hypoxia illustrates the reliance on O2 supply at the other end of the O2 availability spectrum in both sedentary and active populations.     

Muscle phosphocreatine kinetics in children and adults at the onset and offset of moderate-intensity exercise.

The splitting of muscle phosphocreatine (PCr) plays an integral role in the regulation of muscle O2 utilization during a "step" change in metabolic rate. This study tested the hypothesis that the kinetics of muscle PCr would be faster in children compared with adults both at the onset and offset of moderate-intensity exercise, in concert with the previous demonstration of faster phase II pulmonary O2 uptake kinetics in children. Eighteen peri-pubertal children (8 boys, 10 girls) and 16 adults (8 men, 8 women) completed repeated constant work-rate exercise transitions corresponding to 80% of the Pi/PCr intracellular threshold. The changes in quadriceps [PCr], [Pi], [ADP], and pH were determined every 6 s using 31P-magnetic resonance spectroscopy. No significant (P>0.05) age- or sex-related differences were found in the PCr kinetic time constant at the onset (boys, 21+/-4 s; girls, 24+/-5 s; men, 26+/-9 s; women, 24+/-7 s) or offset (boys, 26+/-5 s; girls, 29+/-7 s; men, 23+/-9 s; women 29+/-7 s) of exercise. Likewise, the estimated theoretical maximal rate of oxidative phosphorylation (Qmax) was independent of age and sex (boys, 1.39+/-0.20 mM/s; girls, 1.32+/-0.32 mM/s; men, 2.36+/-1.18 mM/s; women, 1.51+/-0.53 mM/s). These results are consistent with the notion that the putative phosphate-linked regulation of muscle O2 utilization is fully mature in peri-pubertal children, which may be attributable to a comparable capacity for mitochondrial oxidative phosphorylation in child and adult muscle.     

Feedback effects of circulating norepinephrine on sympathetic outflow in healthy subjects

The amplitude of low-frequency (LF) oscillations of heart rate (HR) usually reflects the magnitude of sympathetic activity, but during some conditions, e.g., physical exercise, high sympathetic activity results in a paradoxical decrease of LF oscillations of HR. We tested the hypothesis that this phenomenon may result from a feedback inhibition of sympathetic outflow caused by circulating norepinephrine (NE). A physiological dose of NE (100 ng.kg(-1).min(-1)) was infused into eight healthy subjects, and infusion was continued after alpha-adrenergic blockade [with phentolamine (Phe)]. Muscle sympathetic nervous activity (MSNA) from the peroneal nerve, LF (0.04-0.15 Hz) and high frequency (HF; 0.15-0.40 Hz) spectral components of HR variability, and systolic blood pressure variability were analyzed at baseline, during NE infusion, and during NE infusion after Phe administration. The NE infusion increased the mean blood pressure and decreased the average HR (P < 0.01 for both). MSNA (10 +/- 2 vs. 2 +/- 1 bursts/min, P < 0.01), LF oscillations of HR (43 +/- 13 vs. 35 +/- 13 normalized units, P < 0.05), and systolic blood pressure (3.1 +/- 2.3 vs. 2.0 +/- 1.1 mmHg2, P < 0.05) decreased significantly during the NE infusion. During the NE infusion after PHE, average HR and mean blood pressure returned to baseline levels. However, MSNA (4 +/- 2 bursts/min), LF power of HR (33 +/- 9 normalized units), and systolic blood pressure variability (1.7 +/- 1.1 mmHg2) remained significantly (P < 0.05 for all) below baseline values. Baroreflex gain did not change significantly during the interventions. Elevated levels of circulating NE cause a feedback inhibition on sympathetic outflow in healthy subjects. These inhibitory effects do not seem to be mediated by pressor effects on the baroreflex loop but perhaps by a presynaptic autoregulatory feedback mechanism or some other mechanism that is not prevented by a nonselective alpha-adrenergic blockade.     

Persistent alterations in heart rate variability, baroreflex sensitivity, and anxiety-like behaviors during development of heart failure in the rat

Depressed heart rate variability and mood are associated with increased mortality in patients with congestive heart failure (CHF). Here autonomic indexes were assessed 3 and 7 wk after left coronary artery ligation in telemetered rats, after which anxiety-like behaviors were assessed in an elevated plus maze. Low frequency (LF) and high frequency (HF) heart rate variability were reduced in CHF rats 3 wk after infarction (LF, 1.60 +/- 0.52 vs. 6.97 +/- 0.79 ms(2); and HF, 1.53 +/- 0.39 vs. 6.20 +/- 1.01 ms(2); P < 0.01). The number of sequences of interbeat intervals that correlated with arterial pressure was decreased in CHF rats at 3 and 7 wk (week 3, 26.60 +/- 10.85 vs. 59.75 +/- 11.4 sequences, P < 0.05; and week 7, 20.80 +/- 8.97 vs. 65.38 +/- 5.89 sequences, P < 0.01). Sequence gain was attenuated in CHF rats by 7 wk (1.34 +/- 0.06 vs. 2.70 +/- 0.29 ms/mmHg, P < 0.01). Coherence between interbeat interval and mean arterial blood pressure variability in the LF domain was reduced in CHF rats at 3 (0.12 +/- 0.03 vs. 0.26 +/- 0.05 k(2), P < 0.05) and 7 (0.16 +/- 0.02 vs. 0.31 +/- 0.05 k(2), P < 0.05) wk. CHF rats invariably entered the open arm of the elevated plus maze first and spent more time in the open arms (36.0 +/- 15% vs. 4.6 +/- 1.9%, P < 0.05). CHF rats also showed a tendency to jump head first off the apparatus, whereas controls did not. Together the data indicate that severe autonomic dysfunction is accompanied by escape-seeking behaviors in rats with verified CHF.