Extracellular bicarbonate and non-bicarbonate buffering against lactic acid during and after exercise

Defense of extracellular pH constancy against lactic acidosis can be estimated from changes (Δ) in lactic acid ([La]), [HCO₃⁻], pH and PCO₂ in blood plasma because it is equilibrated with the interstitial fluid. These quantities were measured in earlobe blood during and after incremental bicycle exercise in 13 untrained (UT) and 21 endurance-trained (TR) males to find out if acute and chronic exercise influence the defense. During exercise the capacity of non-bicarbonate buffers (β_nbi = −Δ[La] · ΔpH⁻¹ − Δ[HCO₃⁻] · ΔpH⁻¹) available for the extracellular fluid (mainly hemoglobin, dissolved proteins and phosphates) amounted to 32 ± 2(SEM) and 20 ± 2 mmol l⁻¹ in UT and TR, respectively (P < 0.02). During recovery β_nbi decreased to 14 (UT) and 12 (TR) mmol l⁻¹ (both P < 0.001) corresponding to values previously found at rest by in vivo CO₂ titration. Bicarbonate buffering (β_bi) amounted to 44–48 mmol l⁻¹ during and after exercise. The large exercise β_nbi seems to be mainly caused by an increasing concentration of all buffers due to shrinking of the extracellular volume, exchange of small amounts of HCO₃⁻ or H⁺ with cells and delayed HCO₃⁻ equilibration between plasma and interstitial fluid. Increase of [HCO₃⁻] during titration by these mechanisms augments total β and thus the calculated β_nbi more than β_bi because it reduces ΔpH and Δ[HCO₃⁻] at constant Δ[La]. The smaller rise in exercise β_nbi in TR than UT may be caused by an increased extracellular volume and an improved exchange of La⁻, HCO₃⁻ and H⁺ between trained muscles and blood.     

Extracellular pH defense against lactic acid in normoxia and hypoxia before and after a Himalayan expedition

The extracellular pH defense against the lactic acidosis resulting from exercise can be estimated from the ratios −Δ[La] · ΔpH⁻¹ (where Δ[La] is change in lactic acid concentration and ΔpH is change in pH) and Δ[HCO₃ ⁻] · ΔpH⁻¹ (where Δ[HCO₃ ⁻] is change in bicarbonate concentration) in blood plasma. The difference between −Δ[La] · ΔpH⁻¹ and Δ[HCO₃ ⁻] · ΔpH⁻¹ yields the capacity of available non-bicarbonate buffers (mainly hemoglobin). In turn, Δ[HCO₃ ⁻] · ΔpH⁻¹ can be separated into a pure bicarbonate buffering (as calculated at constant carbon dioxide tension) and a hyperventilation effect. These quantities were measured in 12 mountaineers during incremental exercise tests before, and 7–8 days (group 1) or 11–12 days (group 2) after their return from a Himalayan expedition (2800–7600 m altitude) under conditions of normoxia and acute hypoxia. In normoxia −Δ[La] · ΔpH⁻¹ amounted to [mean (SEM)] 92 (6) mmol · l⁻¹ before altitude, of which 19 (4), 48 (1) and 25 (3) mmol · l⁻¹ were due to hyperventilation, bicarbonate and non-bicarbonate buffering, respectively. After altitude −Δ[La] · ΔpH⁻¹ was increased to 128 (12) mmol · l⁻¹ (P < 0.01) in group 1 and decreased to 72 (5) mmol · l⁻¹ in group 2 (P < 0.05), resulting mainly from apparent large changes of non-bicarbonate buffer capacity, which amounted to 49 (14) mmol · l⁻¹ in group 1 and to 10 (2) mmol · l⁻¹ in group 2. In acute hypoxia the apparent increase in non-bicarbonate buffers of group 1 was even larger [140 (18) mmol · l⁻¹]. Since the hemoglobin mass was only modestly elevated after descent, other factors must play a role. It is proposed here that the transport of La⁻ and H⁺ across cell membranes is differently influenced by high-altitude acclimatization. Accepted: 14 September 2000     

Causes of differences in exercise-induced changes of base excess and blood lactate

It has been concluded from comparisons of base excess (BE) and lactic acid (La) concentration changes in blood during exercise-induced acidosis that more H⁺ than La⁻ leave the muscle and enter interstitial fluid and blood. To examine this, we performed incremental cycle tests in 13 untrained males and measured acid–base status and [La] in arterialized blood, plasma, and red cells until 21 min after exhaustion. The decrease of actual BE (−ΔABE) was 2.2 ± 0.5 (SEM) mmol l⁻¹ larger than the increase of [La]_blood at exhaustion, and the difference rose to 4.8 ± 0.5 mmol l⁻¹ during the first minutes of recovery. The decrease of standard BE (SBE), a measure of mean BE of interstitial fluid (if) and blood, however, was smaller than the increase of [La] in the corresponding volume (Δ[La]_if+blood) during exercise and only slightly larger during recovery. The discrepancy between −ΔABE and Δ[La]_blood mainly results from the Donnan effect hindering the rise of [La]_erythrocyte to equal values like [La]_plasma. The changing Donnan effect during acidosis causes that Cl⁻ from the interstitial fluid enter plasma and erythrocytes in exchange for HCO₃⁻. A corresponding amount of La⁻ remains outside the blood. SBE is not influenced by ion shifts among these compartments and therefore is a rather exact measure of acid movements across tissue cell membranes, but changes have been compared previously to Δ[La]_blood instead to Δ[La]_if+blood. When performing correct comparisons and considering Cl⁻/HCO₃⁻ exchange between erythrocytes and extracellular fluid, neither the use of ΔABE nor of ΔSBE provides evidence for differences in H⁺ and La⁻ transport across the tissue cell membranes.     

HCO<Subscript>3</Subscript><Superscript>−</Superscript>-dependent transient acidification induced by ionomycin in rat submandibular acinar cells

Ionomycin (IM, 5 μM), which exchanges 1 Ca²⁺ for 1 H⁺, changed intracellular pH (pH_i) with Ca²⁺ entry into rat submandibular acinar cells. IM-induced changes in pH_i consisted of two components: the first is an HCO₃ ⁻-dependent transient pH_i decrease, and the second is an HCO₃ ⁻-independent gradual pH_i increase. IM (1 μM), which activates store-operated Ca²⁺ channels, induced an HCO₃ ⁻-dependent and transient pH_i decrease without any HCO₃ ⁻-independent pH_i increase. Thus, a gradual pH_i increase was induced by the Ca²⁺/H⁺ exchange. The HCO₃ ⁻-dependent and transient pH_i decrease induced by IM was abolished by acetazolamide, but not by methyl isobutyl amiloride (MIA) or diisothiocyanatostilbene disulfonate (DIDS), suggesting that the Na⁺/H⁺ exchange, the Cl⁻/HCO₃ ⁻ exchange, or the Na⁺-HCO₃ ⁻ cotransport induces no transient pH_i decrease. Thapsigargin induced no transient pH_i decrease. Thus, IM, not Ca²⁺ entry, reduced pH_i transiently. IM reacts with Ca²⁺ to produce H⁺ in the presence of \textCO ₂ /\textHCO ₃ ^- :  [ \textH - \textIM ] ^- + \text Ca ²⁺  + \textCO ₂ \rightleftarrows [ \textH-\textCa - \textIM ] ⁺ ·\textHCO ₃ ^- + \textH ⁺ {\text{CO}}_{ 2} /{\text{HCO}}_{ 3}{^{ - }} : \, \left[ {{\text{H}} - {\text{IM}}} \right]^{ - } + {\text{ Ca}}^{ 2+ } \,+ {\text{CO}}_{ 2} \rightleftarrows \left[ {{\text{H}}-{\text{Ca}} - {\text{IM}}} \right]^{ + } \cdot {\text{HCO}}_{ 3}{^{ - } }+ {\text{H}}^{ + } . In this reaction, a monoprotonated IM reacts with Ca²⁺ and CO₂ to produce an electroneutral IM complex and H⁺, and then H⁺ is removed from the cells via CO₂ production. Thus, IM transiently decreased pH_i. In conclusion, in rat submandibular acinar cells IM (5 μM) transiently reduces pH_i because of its chemical characteristics, with HCO₃ ⁻ dependence, and increases pH_i by exchanging Ca²⁺ for H⁺, which is independent of HCO₃ ⁻.     

High-intensity exercise decreases muscle buffer capacity via a decrease in protein buffering in human skeletal muscle

We have previously reported an acute decrease in muscle buffer capacity (βm_{in vitro}) following high-intensity exercise. The aim of this study was to identify which muscle buffers are affected by acute exercise and the effects of exercise type and a training intervention on these changes. Whole muscle and non-protein βm_{in vitro} were measured in male endurance athletes (VO_2max = 59.8 ± 5.8 mL kg⁻¹ min⁻¹), and before and after training in male, team-sport athletes (VO_2max = 55.6 ± 5.5 mL kg⁻¹ min⁻¹). Biopsies were obtained at rest and immediately after either time-to-fatigue at 120% VO_2max (endurance athletes) or repeated sprints (team-sport athletes). High-intensity exercise was associated with a significant decrease in βm_{in vitro} in endurance-trained males (146 ± 9 to 138 ± 7 mmol H⁺·kg d.w.⁻¹·pH⁻¹), and in male team-sport athletes both before (139 ± 9 to 131 ± 7 mmol H⁺·kg d.w.⁻¹·pH⁻¹) and after training (152 ± 11 to 142 ± 9 mmol H⁺·kg d.w.⁻¹·pH⁻¹). There were no acute changes in non-protein buffering capacity. There was a significant increase in βm_{in vitro} following training, but this did not alter the post-exercise decrease in βm_{in vitro}. In conclusion, high-intensity exercise decreased βm_{in vitro} independent of exercise type or an interval-training intervention; this was largely explained by a decrease in protein buffering. These findings have important implications when examining training-induced changes in βm_{in vitro}. Resting and post-exercise muscle samples cannot be used interchangeably to determine βm_{in vitro}, and researchers must ensure that post-training measurements of βm_{in vitro} are not influenced by an acute decrease caused by the final training bout.     

Assessment of post-competition peak blood lactate in male and female master swimmers aged 40–79 years and its relationship with swimming performance

The main purpose of this study was to measure the post-competition blood lactate concentration ([La]_b) in master swimmers of both sexes aged between 40 and 79 years in order to relate it to age and swimming performance. One hundred and eight swimmers participating in the World Master Championships were assessed for [La]_b and the average rate of lactate accumulation (La′; mmol l⁻¹ s⁻¹) was calculated. In addition, 77 of them were also tested for anthropometric measures. When the subjects were divided into 10-year age groups, males exhibited higher [La]_b than women (factorial ANOVA, P < 0.01) and a steeper decline with ageing than female subjects. Overall, mean values (SD) of [La]_b were 10.8 (2.8), 10.3 (2.0), 10.3 (1.9), 8.9 (3.2) mmol l⁻¹ in women, and 14.2 (2.5), 12.4 (2.5), 11.0 (1.6), 8.2 (2.0) mmol l⁻¹ in men for, respectively, 40–49, 50–59, 60–69, 70–79 years’ age groups. When, however, [La]_b values were normalised for a “speed index”, which takes into account swimming speed as a percentage of world record, these sex-related differences, although still present, were considerably attenuated. Furthermore, the differences in La′ between males and females were larger in the 40–49 age group (0.34 vs 0.20 mmol l⁻¹ s⁻¹ for 50-m distance) than in the 70–79 age group (0.12 vs 0.14 mmol l⁻¹ s⁻¹ for 50-m distance). Different physiological factors, supported by the considered anthropometric measurements, are suggested to explain the results.     

Peripheral markers of central fatigue in trained and untrained during uncompensable heat stress

The development of fatigue is more pronounced in the heat than thermoneutral environments; however, it is unclear whether biomarkers of central fatigue are consistent with the higher core temperature (T _c) tolerated by endurance trained (TR) versus untrained (UT) during exertional heat stress (EHS). The purpose of this study was to examine the indicators of central fatigue during EHS in TR versus UT. Twelve TR and 11 UT males (mean ± SE [(V)\dot]\textO _{2 \textpeak} \dot{V}{\text{O}}_{{ 2 {\text{peak}}}}  = 70 ± 2 and 50 ± 1 mL kg LBM⁻¹ min⁻¹, respectively) walked on a treadmill to exhaustion (EXH) in 40°C (dry) wearing protective clothing. Venous blood was obtained at PRE and 0.5°C T _c increments from 38 to 40°C/EXH. Free tryptophan (f-TRP) decreased dramatically at 39.5°C for the TR. Branch chain amino acids decreased with T _c and were greater for UT than TR at EXH. Tyrosine and phenylalanine remained unchanged. Serum S100β was undetectable (<5 pg mL⁻¹). Albumin was greater for the UT from PRE to 39.0°C and at EXH. Prolactin (PRL) responded to relative thermal strain with similar EXH values despite higher T _c tolerated for TR (39.7 ± 0.09°C) than UT (39.0 ± 0.09°C). The high EXH PRL values for both groups support its use as a biomarker of the serotonin and dopamine interplay within the brain during the development of central fatigue.     

pH-regulatory mechanisms in in vitro perfused rectal gland tubules of Squalus acanthias

 Isolated in vitro perfused rectal gland tubules (RGT) were preincubated with the pH-sensitive dye 2′,7′-bis(carboxyethyl)-5(6)-carboxyfluorescein (BCECF) and pH-regulatory mechanisms were studied. A reduction of bath Cl^– concentration from 269 to 6 mmol/l increased the fluorescence ratio 488/436 [corresponding to cytosolic pH (pH_i)] slightly but significantly (n=10). Depolarization by Ba²⁺ (1 mmol/l) or a bath solution containing 30 mmol/l K⁺ (n=4–6) increased the fluorescence ratio (pH_i). These data suggest that HCO₃ ^– uptake and/or H⁺ extrusion is dependent on Cl^– and/or voltage. A reduction of bath Na⁺ from 278 to 5 mmol/l reduced the ratio significantly (n=3). Addition of trimethylamine (Trima⁺, 20 mmol/l) alkalinized cytosolic pH (n=7). Similarly, addition of NH₄ ⁺ (20 mmol/l) led to an initial alkalinization and a strong acidification when NH₄ ⁺ was removed (n=59). The initial pH_i-recovery rates after NH₄ ⁺ removal were quantified and the responsible H⁺ extrusion and/or HCO₃ ^– import systems were examined. The recovery was almost completely abolished when the extracellular Na⁺ concentration was reduced to 5 mmol/l. In the presence of normal Na⁺, recovery was slower in the absence as compared to the presence of HCO₃ ^– (n=5). It was inhibited by 4,4′-diisothiocyanatostilbene-2,2′-disulphonic acid (DIDS) (0.5 mmol/l, n=11) in the presence of HCO₃ ^– and in the absence of HCO₃ ^– by the Na⁺/H⁺-exchange blocker HOE694 (0.5 mmol/l, n=6). These data suggest that acid extrusion probably occurs by basolateral Na⁺-2HCO₃ ^–/Cl^– exchange in the presence of HCO₃ ^– and by basolateral Na⁺/H⁺ exchange in the absence of HCO₃ ^–. Luminal perfusion with a solution containing a low Cl^– concentration (6 mmol/l) increased the fluorescence ratio (pH_i) (n=5). The ratio (pH_i) was further increased and pH recovery further delayed by basolateral addition of Trima⁺ (20 mmol/l, n=3). These data suggest that the HCO₃ ^–/Cl^– exchanger is present in the luminal membrane. Luminal HCO₃ ^–/Cl^– exchange and basolateral Na⁺-2HCO₃ ^–/Cl^– exchange may work in tandem to secrete HCO₃ ^– and exchange it for luminal Cl^–. Received: 7 January 1998 / Received after revision and accepted: 5 March 1998     

Cultured ruminal epithelial cells express a large-conductance channel permeable to chloride, bicarbonate, and acetate

The absorption of short-chain fatty acids (SCFA) from the rumen requires efficient mechanisms for both apical uptake and basolateral extrusion. Previous studies suggest that the rumen expresses a basolateral chloride conductance that might be permeable to SCFA. In order to characterize this conductance in more detail, isolated cultured ruminal epithelial cells were studied with the patch-clamp technique, revealing a whole-cell conductance with p(Cl⁻) ≈ p(NO₃ ⁻) > p(HCO₃ ⁻) > p(acetate⁻) > p(gluconate⁻). Currents could be blocked by diisothiocyanato-stilbene-2,2′-disulfonic acid (1 mmol l⁻¹ > 100 μmol l⁻¹), 5-nitro-2-(3-phenylpropyl-amino)benzoic acid (50 μmol l⁻¹), niflumic acid (100 μmol l⁻¹), and p-chloromercuribenzoate (1 mmol l⁻¹). Single-channel conductance was 350 ± 7 pS for chloride and 142 ± 7 pS for acetate. Open probability could be fitted with a three-state gating model. We propose a role for this channel in mediating the permeation of chloride, bicarbonate, and acetate across the basolateral membrane of the ruminal epithelium.     

Effects of endurance training on intracellular calcium concentration in T lymphocytes

The purpose of the present study was to determine whether 12 months of endurance training reduced [Ca²⁺]i in T helper (CD4⁺) lymphocytes in trained (TR) men compared to untrained (UT). Fourteen trained (Ironman triathletes) and nine untrained (sedentary) men volunteered for the study. The TR group averaged 12 km of swimming, 300 km of cycling and 60 km of running per week during the year. Resting blood samples were taken from TR (VO_2peak 64 ± 2 ml kg⁻¹ min⁻¹) and UT (VO_2peak 42 ± 2 ml kg⁻¹ min⁻¹) subjects every 4 weeks for 52 weeks (October 1, 1999–October 1, 2000). Leukocyte concentration was measured using a full blood count. Unstimulated CD4⁺ lymphocytes were separated and analysed for changes in free ([Ca²⁺]i) and total ([Ca²⁺]t) calcium using flow cytometry. There were no significant differences in leukocyte concentration between UT and TR groups. There were significant differences between TR and UT in [Ca²⁺]i (October B and November), and [Ca²⁺]t (January and March). There were also significant sequential monthly changes in both [Ca²⁺]i and [Ca²⁺]t for TR and UT groups during the study. Significant increases in [Ca²⁺]i and [Ca²⁺]t during summer (January and March) for both TR and UT groups suggest an increase in intracellular signalling during hot weather. [Ca²⁺]i and [Ca²⁺]t were significantly lower in TR lymphocytes during November and March, suggesting that endurance training during warmer months may decrease [Ca²⁺]i through altered intracellular signalling, possibly to maintain lymphocyte function during heat stress.     

Aerobic training increases the stimulated percentage of CD4<Superscript>+</Superscript>CD25<Superscript>+</Superscript> in older men but not older women

The purpose of the present study was to determine whether 12 months of moderate intensity cycling would increase the expression of IL-2 (CD25⁺) receptors in T helper (CD4⁺) lymphocytes in men and women aged 65–75 years. Fourteen men and 10 women completed 52 weeks of moderate intensity cycling (60% VO₂peak). Subjects trained (TR) three times per week for 45 min per session. Eight age-matched untrained (UT) male and eight UT female subjects acted as controls. Resting blood samples were taken from TR and UT subjects every 4 weeks. Leukocyte concentration was measured using a full blood count. PHA-stimulated CD4⁺ lymphocytes were analysed for changes in the expression of CD25⁺, by flow cytometry. Training significantly increased VO_2peak (l min⁻¹, ml kg⁻¹ min⁻¹) in male (+14.3, +16%) and female (+16.7, +27.8%) groups. The TR male group showed a significantly lower percentage of CD4⁺CD25⁺ than the male UT in January but the TR male percentage was significantly higher than the UT male group during February, March, April, May, June, September B and December. The female TR group showed a significantly higher percentage CD4⁺CD25⁺ than the female UT only during July. There were also significant sequential monthly changes in the percentage of CD4⁺CD25⁺ for male and female UT and TR groups. Significant increases in the percentage of CD4⁺CD25⁺ in the male TR group suggest training-enhanced lymphocyte mitogenic responsiveness. Moderate intensity long-term training may increase the recruitment of active memory CD4⁺CD25⁺ in men rather than women.     

In vivo 4-androstene-3,17-dione and 4-androstene-3β,17β-diol supplementation in young men

To determine if known androgenic hormone precursors for testosterone in the androgen pathway would be readily transformed to testosterone, eight male subjects [mean age 23.8 (SEM 3) years, bodymass 83.1 (SEM 8.7) kg, height 175.6 (SEM 8.5) cm] underwent a randomized, double-blind, cross-over, placebo-controlled oral treatment with 200 mg of 4-androstene-3,17-dione (Δ4), 4-androstene-3β,17β-diol (Δ4Diol), and placebo (PL). The periods of study were separated by 7 days of washout. Blood was drawn at baseline and subsequently every 30 min for 90 min after treatment. Analysis revealed mean area-under-the-curve (AUC) serum Δ4 concentrations to be higher during Δ4 treatment [2177 (SEM 100) nmol · l⁻¹] than Δ4Diol [900 (SEM 96) nmol · l⁻¹] or PL [484 (SEM 82) nmol · l⁻¹; P < 0.0001]. The Δ4 treatment also revealed a significant effect on total testosterone with a mean AUC [1632.5 (SEM 121) nmol · l⁻¹] that was greater than PL [1418.5 (SEM 131) nmol · l⁻¹; P < 0.05] but not significantly different from those observed after Δ4Diol treatment [1602.9 (SEM 119) nmol · l⁻¹; P = 0.77]. Free testosterone concentrations followed a similar pattern where mean AUC for the Δ4 treatment [6114.0 (SEM 600) pmol · l⁻¹] was greater than after PL [4974.6 (SEM 565) pmol · l⁻¹; P < 0.06] but not significantly different from those observed after Δ4Diol [5632.0 (SEM 389) pmol · l⁻¹; P = 0.48]. The appearance and apparent conversion to total and free testosterone over 90 min was stronger for the Δ4 treatment (r = 0.91, P < 0.045) than for Δ4Diol treatment (r = 0.69, NS) and negatively correlated for PL (r = −0.90, P < 0.02). These results would suggest that Δ4, and perhaps Δ4Diol, taken by month are capable of producing in vivo increases in testosterone concentrations in apparently healthy young men as has already been observed in women after treatment with Δ4. Accepted: 26 August 1999     

Effect of the intensity of training on catecholamine responses to supramaximal exercise in endurance-trained men

In this study we investigated whether plasma catecholamine responses to the Wingate test are affected by the intensity of training in endurance-trained subjects. To do this we compared plasma adrenaline (A) and noradrenaline (NA) concentrations in response to a Wingate test in three different groups: specialist middle-distance runners (MDR) in 800-m and 1,500-m races, specialist long-distance runners (LDR) 5,000-m and 10,000-m races, and untrained subjects (UT). The maximal power (W _max) and the mean power (W) were determined from the Wingate test. Blood lactate (La), plasma A and NA concentrations were analysed at rest (La₀, A₀ and NA₀), immediately at the end of the exercise (A_max and NA_max) and after 5 min recovery (La_max, A₅ and NA₅). The ratio A_max/NA_max was considered as an index of the adrenal medulla responsiveness to the sympathetic nervous activity. At the end of the test, W _max and W were similar in the three groups but La_max was significantly greater in MDR compared to LDR and UT [15.2 (2.2) mmol l^–1, 11.7 (3.1) mmol l^–1, 11.6 (1.6) mmol l^–1, respectively, for MDR, LDR and UT; mean (SD)]. Concerning the plasma catecholamine concentrations in response to exercise, MDR and LDR A_max values [3.73 (1.53) nmol l^–1, 3.47 (0.74) nmol l^–1, respectively, for MDR and LDR] were significantly greater than those of UT [1.48 (0.32) nmol l^–1] who also exhibited the lowest NA_max values [11.09 (6.58) nmol l^–1] compared to MDR and LDR [20.43 (3.51) nmol l^–1; 15.85 (4.88) nmol l^–1, respectively, for MDR and LDR]. However, no significant differences were observed between the two trained groups either for A_max or NA_max. These results suggest that long-term endurance training can enhance plasma catecholamine concentrations in response to supramaximal exercise. However, as there were no significant differences between MDR and LDR A_max and NA_max values, the effect of the intensity of training remains to be clarified.     

Changes in the countercurrent system in the renal papilla: diuresis increases pH and HCO 3 − gradients between collecting duct and vasa recta

This study was designed to elucidate the acid-base balance local to the collecting duct urine (CD) and vasa recta blood (VR) in the rat renal papilla in diuresis. The pH changes were measured in both a furosemide-induced and a volume-load-induced diuresis, whereas the PCO₂ (i.e., CO₂ tension) and HCO₃ ⁻ concentration were measured only in a furosemide-induced diuresis. In an antidiuresis, the pH of the VR was more acidic than that of the systemic arterial blood (ΔpH = 0.44–0.73). Additionally, the pH of the ascending VR was significantly lower than that of the descending VR (ΔpH = 0.14–0.16). In diuresis, the pH of the CD decreased (ΔpH = 0.81–0.97), while the pH of the descending and the ascending VR increased; however, the increase was only significant in the ascending VR (ΔpH = 0.23–0.30). Consequently, the significant difference in the pH gradient between the descending and the ascending VR was eliminated. The PCO₂ values in the CD and the ascending VR were not different from those in antidiuresis, while the HCO₃ ⁻ concentration in the CD and the ascending VR, respectively, decreased and increased significantly. Thus, in diuresis, the decrease in the pH of the CD and the increase in the pH of the ascending VR result, respectively, from the decrease and the increase in the HCO₃ ⁻ concentration, with no changes in the PCO₂ values. Received: 5 February 1996/Received after revision and accepted: 20 May 1996     

Effects of bicarbonate ingestion and high intensity exercise on lactate and H(+)-ion distribution in different blood compartments

Lactate (La) and H⁺-ions are unequally distributed in the blood between plasma and red blood cells (RBCs). To our knowledge there is no data concerning the effects of an oral ingestion of bicarbonate (HCO₃ ⁻) on repeated high intensity sprint exercise and La and H⁺ distribution between plasma and RBCs. Since an oral ingestion of HCO₃ ⁻ leads to a higher efflux of La from the working skeletal muscle to the plasma, as it was shown by previous studies, this would lead to a higher gradient of La between plasma and RBCs. Although a higher gradient leads to a higher uptake, it is even more difficult for the RBCs to take up La fast enough, due to the more stressed transport system. Since RBCs function to transport La from the working muscle and help to maintain a concentration difference between plasma and muscle, this potentially increases performance during repeated sprint exercise (e.g. 4 × 30 s). The major goal of the present investigation was to test this hypothesis. 11 male participants ingested either a solution of sodium bicarbonate (NaHCO₃) or placebo (CaCO₃). Thereafter all performed four maximal 30 s sprints with 5 min of passive rest. During the resting periods concentrations of HCO₃ ⁻, La and H⁺ where measured in both blood compartments (plasma and RBCs). There were no significant differences in the La-ratios between plasma and RBCs between both interventions. These results indicate that the La/H⁺ co-transport is not affected by an oral ingestion on NaHCO₃.     

Exercise with hypoventilation induces lower muscle oxygenation and higher blood lactate concentration: role of hypoxia and hypercapnia

Eight men performed three series of 5-min exercise on a cycle ergometer at 65% of normoxic maximal O₂ consumption in four conditions: (1) voluntary hypoventilation (VH) in normoxia (VH_0.21), (2) VH in hyperoxia (inducing hypercapnia) (inspired oxygen fraction [F_IO₂] = 0.29; VH_0.29), (3) normal breathing (NB) in hypoxia (F_IO₂ = 0.157; NB_0.157), (4) NB in normoxia (NB_0.21). Using near-infrared spectroscopy, changes in concentration of oxy-(Δ[O₂Hb]) and deoxyhemoglobin (Δ[HHb]) were measured in the vastus lateralis muscle. Δ[O₂Hb − HHb] and Δ[O₂Hb + HHb] were calculated and used as oxygenation index and change in regional blood volume, respectively. Earlobe blood samples were taken throughout the exercise. Both VH_0.21 and NB_0.157 induced a severe and similar hypoxemia (arterial oxygen saturation [SaO₂] < 88%) whereas SaO₂ remained above 94% and was not different between VH_0.29 and NB_0.21. Arterialized O₂ and CO₂ pressures as well as P50 were higher and pH lower in VH_0.21 than in NB_0.157, and in VH_0.29 than in NB_0.21. Δ[O₂Hb] and Δ[O₂Hb − HHb] were lower and Δ[HHb] higher at the end of each series in both VH_0.21 and NB_0.157 than in NB_0.21 and VH_0.29. There was no difference in Δ[O₂Hb + HHb] between testing conditions. [La] in VH_0.21 was greater than both in NB_0.21 and VH_0.29 but not different from NB_0.157. This study demonstrated that exercise with VH induced a lower tissue oxygenation and a higher [La] than exercise with NB. This was caused by a severe arterial O₂ desaturation induced by both hypoxic and hypercapnic effects.     

Role of physiological HCO3 –buffer on intracellular pH and histamine release in rat peritoneal mast cells

 The purpose of this study was to examine how intracellular pH (pH_i) regulation and histamine release are affected by HCO₃ ^–in rat peritoneal mast cells. The pH_i was measured using the pH-sensitive dye 2′, 7′-bis(2-carboxyethyl)-5(6)-carboxyfluorescein (BCECF). We observed a pH_i of 6.88±0.012 (n=24) in resting mast cells exposed to a HEPES buffer (pH 7.4), but a sustained drop of 0.21 pH units to 6.67±0.015 (n=23) when we exposed the mast cells to a HEPES/HCO₃ ^–buffer equilibrated at all time with 5% CO₂ (pH 7.4). This fall in pH_i is inhibited by the carbonic anhydrase inhibitor dichlorphenamide and is Na⁺-independent, indicating the involvement of Na⁺-independent Cl^–/HCO₃ ^–exchange activity. Furthermore removal of external Cl^–in the presence but not in the absence of HCO₃ ^–reversed the Cl^–/HCO₃ ^–exchange and induced an alkaline load. The recovery from this alkaline load was dependent on external Cl^–but independent of Na⁺. Both the alkalinization and the recovery were inhibited by the anion transport inhibitor 4,4′-diisothiocyanatostilbene-2,2′-disulphonic acid (DIDS). In addition, ³⁶Cl^–uptake measurements confirm the presence of a Cl^–/HCO₃ ^–exchanger. Histamine release stimulated by antigen and compound 48/80 was substantially reduced in the presence of HEPES/ HCO₃ ^–buffer (pH_o 7.4, pH_i 6.66). Histamine release was increased, however, when pH_i was clamped to 6.66 in HCO₃ ^–-free media (pH_o 6.9). We conclude that: (1) Na⁺-independent Cl^–/HCO₃ ^–exchange determines steady-state pH_i in rat peritoneal mast cells; and (2) the reduction in histamine release observed in the presence of HCO₃ ^–is not due to its effect on pH_i per se, but rather on other changes in ion transport. Received: 29 January 1998 / Received after revision and accepted: 3 April 1998     

Exercise-induced changes in blood levels of alpha-tocopherol

Levels of α-tocopherol (αT) in plasma and red blood cells (RBC) are assumed to be modulated by exercise. The mechanisms involved remain to be established. We examined the influence of different running bouts on the content of αT in RBC (αT_RBC), the concentration in plasma (αT_plasma), and their relationship with lipolysis, as indicated by changes (Δ) in plasma glycerol concentration ([glycerol]). Eleven healthy runners [mean (SD) age 35 (9) years, height 177.3 (7.6) cm, body mass 69.6 (9.4) kg, and peak oxygen consumption, , 57.8 (4.8) ml^.kg^–1.min^–1] performed an incremental treadmill test [duration 17 (2) min, peak velocity, v _peak 4.8 (0.4) m^.s^–1], a training run [173 (12) min, 57 (4)% v _peak] and a marathon [197 (24) min, 75 (5)% v _peak]. Before (pre) and after (post) each run, haematological and lipid parameters, αT_RBC and αT_Plasma were determined. Haemoconcentration was observed after each run. Δ[glycerol] was +0.10 (0.10) mmol^.l^–1, +0.40 (0.14) mmol^.l^–1 and +0.51 (0.15) mmol^.l^–1 in the treadmill test, training run and marathon, respectively. When corrected for haemoconcentration, values of αT_plasma decreased [–5.4 (7.5)%, P<0.05] in the treadmill test, were unchanged [+0.7 (8.7)%] in the training run and increased [+7.8 (8.3)%, P<0.05] in the marathon. αT_RBC decreased [pre vs post: 22.7 (3.2) nmol^.g haemoglobin^–1 (nmol^.g Hb^–1) vs 18.9 (3.8) nmol^.g Hb^–1, P<0.05] in the treadmill test and was not significantly changed in either the training run [20.8 (1.9) nmol^.g Hb^–1 vs 19.1 (3.0) nmol^.g Hb^–1] or the marathon [21.6 (2.9) nmol^.g Hb^–1 vs 23.4 (2.7) nmol^.g Hb^–1]. ΔαT_RBC and ΔαT_plasma were positively related to Δ[glycerol]. The reduction in αT_RBC and αT_plasma after short-lasting heavy exercise indicates the consumption of αT, whereas the association between ΔαT and Δ[glycerol] suggests mobilisation of αT, especially in long-lasting exercises. However, although αT appears to be influenced by exercise, the results suggest a well-balanced regulation of αT during exercise resulting in small, and only in part, significant ΔαT in blood. Electronic Publication     

Effect of exercise mode on blood glucose disposal during physiological hyperinsulinaemia in humans

The aim of this study was to compare whole-body glucose uptake in cycling and running performed during physiological hyperinsulinaemia. On three occasions, seven male subjects underwent a hyperinsulinaemic (30 mU m⁻² min⁻¹), euglycaemic (5 mmol l⁻¹) clamp for 120 min. On one occasion, subjects rested for the duration of the trial (CON). On the other two occasions, after an initial resting period of 30 min, subjects either cycled (CYC) or ran (RUN) for 90 min at 65% of maximal O₂ uptake (V˙O_2max). Insulin infusion resulted in physiological hyperinsulinaemia that was maintained for the duration of each trial [CON: 61 (3) mU l⁻¹; CYC: 77 (7) mU l⁻¹; RUN: 77 (5) mU l⁻¹]. The rate of glucose uptake was greater during RUN than during CYC [last 30 min of exercise: 140 (4) vs 109 (8) μmol kg⁻¹ min⁻¹, respectively; P <0.01]. A differential amount of active muscle mass and/or muscle fibre type recruitment might account for the observed differences in glucose disposal between cycling and running. Electronic Publication     

Influence of two pedalling rate conditions on mechanical output and physiological responses during all-out intermittent exercise

The purpose of this study was to investigate the effect of two cycling velocities on power output and concomitant metabolic and cardiorespiratory responses to repeated all-out exercises. Mean power output (P _m), total work (W _tot), total oxygen consumption (VO_2tot) and blood lactate accumulation (Δ[La]_b) were evaluated in 13 male subjects who performed two series of twelve 5-s bouts of sprint cycling. Recovery periods of 45-s were allowed between trials. One series was executed at optimal velocity (V _opt: velocity for greatest power) and the other one at 50% V _opt (0.5V _opt). Velocities obtained in these conditions were V_opt=116.6 (4.7) rpm; 0.5V_opt=60.6 (4.9) rpm. After a phase of adaptation in oxygen uptake in the first part of the series, the data from the 6th to the 12th sprint were as follows: P _m, 924.6 (73.9) versus 689.2 (61.8) W; W _tot, 29.95 (4.14) versus 22.04 (3.17) kJ; VO_2tot, 12.80 (1.36) versus 10.58 (1.37) l; Δ[La]_b, 2.72 (1.22) versus 0.64 (0.79) mmol.l⁻¹, respectively (P<0.001). Both W _tot and VO_2tot were consistently higher at optimal velocity (+21 and +35.8%, respectively). The present findings demonstrate that during intermittent short-term all-out exercise requiring maximal activation, the energy turnover is not necessarily maximal. It depends on muscle contraction velocity. The increase, lower than expected, in metabolic response from 0.5V _opt to V _opt suggests also that mechanical efficiency is higher at V _opt. Electronic Publication