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1Institute of Sports Medicine, Bispebjerg Hospital, Bispebjerg Bakke 23, Copenhagen, Denmark; 2Department of Human Biology and Nutritional Sciences, University of Guelph, Guelph, Ontario; 4Department of Medicine, McMaster University, Hamilton, Ontario, Canada; and 3Department of Integrative Biology, University of California-Berkeley, Berkeley, California
Submitted 19 July 2004 ; accepted in final form 6 October 2004
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ABSTRACT |
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 TOP ABSTRACT MATERIALS AND METHODSRESULTSDISCUSSIONGRANTSACKNOWLEDGMENTSREFERENCES |
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O2 peak) exercise with and without LC. During the control (Con) trial, subjects were administered an isotonic, isovolumetric saline infusion. During LC, plasma lactate concentration ([Lac–]) was elevated to 4 meq/l during rest and to 4–7 meq/l during exercise. During LC at rest, there were rapid and transient changes in plasma, erythrocyte, and blood volumes. LC resulted in decreased plasma [H+] (from 39.6 to 29.6 neq/l) at the end of exercise while plasma [HCO3–] increased from 26 to 32.9 meq/l. Increased plasma strong ion difference [SID], due to increased [Na+], was the primary contributor to decreased [H+] and increased [HCO3–]. A decrease in plasma total weak acid concentration also contributed to these changes, whereas PCO2 contributed little. The infusion of hypertonic LC caused only minor volume, acid-base, and CO2 storage responses. We conclude that an LC infusion is appropriate for studies of metabolic regulation. Stewart model; plasma volume; lactate infusion; strong ion difference; lactate transport
On resting subjects, the LC procedure results in increases in plasma pH and [HCO3–] (12, 35), an effect opposite to what occurs on infusion of strong inorganic anions such as Cl–. When circulating [Lac–] is elevated to concentrations in excess of what occurs in response to normal metabolic Lac– production, the result is increased Lac– oxidation and decreased glucose oxidation (29, 30), demonstrating that Lac– has a strong metabolic influence. LC also elicits a decrease in pulmonary respiratory exchange ratio (RER = CO2O2) due to an increase in O2 without a significant change in CO2 (8–10, 29, 30, 35, 40). The RER response is consistent with an increase in whole body HCO3– content, such that the infusion of Na+ with Lac– increases the extracellular content and concentrations of Na+ and HCO3– (12). If the increase in CO2 storage is appreciable, then the measured RER during LC may underestimate carbohydrate oxidation (29, 30). The second purpose of the present investigation was to characterize plasma HCO3– dynamics with LC during rest and prolonged light- to moderate-intensity exercise.
During infusion of hypertonic LC at rest, the facilitated transport of Lac– into cells, concomitant with increased plasma [Na+], alters acid-base balance. The physicochemical properties that define acid-base status of physiological solutions are described by a series of equations, reintroduced by Stewart (39). The physicochemical approach treats physiological solutions as systems possessing three independent variables, the strong ion difference ([SID]), PCO2, and the total weak acid concentration ([Atot]), that determine the dependent variables [H+] and [HCO3–]. Since its introduction, this physicochemical approach to acid-base assessment has been critically evaluated and validated (19, 43, 44). Infusion of hypertonic LC effectively increases plasma [SID] due to the increase in extracellular [Na+] and cellular removal of Lac–, which is also a strong acid anion with pK' = 3.9. In contrast, during high-intensity exercise, production and facilitated transport of Lac– from contracting muscle cells decreases plasma [SID] and, consequently, increases plasma [H+] and decreases [HCO3–] (25, 28). Thus whereas Lac– production and release from contracting muscle cells acidifies the extracellular environment, Lac– export is an important contributor to the regulation of intracellular [H+] within contracting cells (24). Furthermore, because MCTs act as Lac–-H+ cotransporters (18, 34), metabolic and acid-base consequences of Lac– production and transport are linked. Therefore, our third goal was to quantify acid-base responses during periods of increased plasma [Lac–] that exceed metabolic Lac– production to gain insight into the dual role of Lac– as a strong acid anion and metabolic intermediate.
In the present study, we used a sodium-lactate infusion (LC) to elevate plasma [Lac–] during rest and during a light- to moderate-intensity (55% O2 peak) exercise trial, which does not ordinarily result in a large elevation in arterial [Lac–]. We fixed arterial [Lac–] to levels seen during moderate-intensity (65% O2 peak) exercise trial (29), a procedure we previously termed a lactate clamp (LC).
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MATERIALS AND METHODS |
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Study design.
After screening, subjects completed an incremental cycling test (Quinton Excalibur, Quinton Instruments, Seattle, WA) to exhaustion to determine their O2 peak values. Expired gases were collected online (Quinton Q-plex 1, Quinton Instruments) to determine O2 uptake and heart rate responses (Polar Electro Heart Rate Monitor). One to three weeks later, subjects visited the laboratory 3 h after eating a light meal (toast and juice) on two subsequent occasions, separated by 1 wk. Subjects were instructed to eat the same breakfast on the morning of each trial and to refrain from alcohol, caffeine, and exercise for 48 h preceding each trial.
On arrival at the laboratory, subjects were fitted with a heart rate monitor (Polar Electro). The subject was seated for 15 min, at the end of which resting respiratory measurements were collected for a period of 5–10 min. Teflon catheters were inserted into an antecubital vein for LC/control (Con) infusions and into a radial artery for blood sampling. Catheters were kept patent by a constant saline drip (
200 µl/min, 0.9%, no heparin). A baseline blood sample was obtained before initiation of LC or Con infusion. Subjects remained seated in a comfortable chair for a 90-min resting period, which was immediately followed by a 90-min period of light- to moderate-intensity (55% O2 peak) exercise on an electronically braked cycle ergometer.
Subjects were infused with a sodium-lactate solution (LC trial) during the first visit and sodium chloride (Con trial) during the second visit. Accompanying the LC infusion was an isotonic saline infusion to mitigate the potentially irritating effect at the infusion site of low pH and hypertonic infusate. Because the rate of physiological saline infusion was variable, according to each subject's comfort to the infusate, LC was always performed before the Con trial. The Con trials consisted of an isotonic saline infusion at a rate and volume matching those used in the LC trial. The Con and LC trials were performed at identical work rates.
LC trials were performed with a sodium lactate/lactic acid mixture prepared by mixing 88% (L+) lactic acid (PCCA, Houston, TX) with 2N NaOH (Spectrum Chemicals, Auburn, WA), yielding a solution with pH 4.8. The individual components were United States Pharmacopeia-National Formulary (USP-NF) certified and tested to be sterile and negative for pyrogenicity (University of California, San Francisco, School of Pharmacy). The infusion was delivered with calibrated peristaltic pumps (IVAC 572, Alaris Medical Systems, Markham, ON, Canada) at rates approximating our previous LC trials to achieve a target plasma [Lac–] of 4 meq/l during rest and values approximating those found during 65% O2 peak exercise (29, 30). During LC, subjects received an average lactate infusion rate of 0.032 and 0.037 mmol·kg–1·min–1 during rest and exercise, respectively (Table 1), amounting to 239 mmol at rest and 276 mmol during exercise. The average volumes of LC solution infused were 182.5 and 211 ml during rest and exercise, respectively, and this was matched by equal volumes of isotonic saline for a total average infusate volume of 787 ml. A total of 36 ml of saline was dripped in via the arterial line. Thus, in the Con trial, the total volume of saline averaged 823 ml and 429.5 ml in the LC trial. The LC infusate had a [Lac–] of 1.3 eq/l, and when mixed with an equal volume delivery of isotonic saline, the solution entering the vein had an average [Lac–] of 650 meq/l. The LC infusate had a [Na+] of 1.07 eq/l, and when mixed with an equal volume delivery of isotonic saline, the solution entering the vein had an average [Na+] of 610 meq/l. Thus infusate osmolarity was 1,300 mosmol/kgH2O, with a total volume of 823 ml infused over 180 min; the total amount of Na+ infused averaged 502 meq.
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Subjects remained seated in a comfortable chair for a 90-min resting period during which blood was sampled at 0, 10, 20, 30, 60, and 90 min of rest. During exercise, blood was sampled at 10, 20, 30, 60, and 90 min. Respiratory gases were analyzed at 0, 30, 60, and 90 min of rest, and exercise. Samples were collected during a 7-min period before blood sampling with the first 2-min period disregarded to allow proper equilibration. These gases were used for calculation of O2, CO2, E, and RER (CO2/O2).
Blood samples were collected anaerobically from a radial artery in 7-ml tubes containing lithium-heparin (10 IU lithium heparin/ml; Sarstedt, Numbrecht, Germany). Blood was immediately analyzed for Hct (by electrical conductivity; calibrated to microcapillary tube centrifugation), plasma strong ions (Na+, K+, Cl–, Lac–), gases, and pH (Nova StatProfile 9+ blood gas/electrolyte analyzer; Nova Biomedical, Waltham, MA). Plasma [HCO3–] was calculated from measured plasma PCO2 and pH using the Henderson-Hasselbach equation. A portion of the whole blood sample was analyzed for total hemoglobin content (Radiometer OSM3 hemoximeter, Copenhagen, Denmark). Remaining blood was separated into two aliquots. One milliliter of blood was hemolyzed [by repeated (4 times) freezing in liquid nitrogen and thawing in warm water] for analysis of whole blood ion concentrations. Remaining blood was immediately centrifuged at 15,000 g for 5 min, and the plasma was removed for analysis of total protein concentration ([PP]) using a clinical refractometer (Atago model 331, Atago, Japan).
Calculations
Hematology.
Percent change in the volumes of blood (%
BV), plasma (%PV), and erythrocyte (%EV) were calculated as detailed previously (15, 27):
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Physicochemical calculations.
Calculations of physicochemical parameters were made using AcidBasics II software (2003; PD Watson). Plasma [SID] was calculated as the sum of the strong cation concentrations minus the sum of the strong anion concentrations (39):
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Erythrocyte ion concentration (meq/l cell water) was calculated as:
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The contributions of each of the independent variables ([SID], [Atot], and PCO2), to the dependent variables ([H+] and [HCO3–]), were determined by holding two of the three independent variables constant while calculating [H+] and [HCO3–] in response to changes in the third independent variable (25).
Statistics
Data are presented as means ± SE. Work rate, heart rate, and respiratory parameters were compared by one-way ANOVA with differences determined by the least significant squares post hoc test. Significant changes over time were determined by a two-way (treatment and time) repeated-measures ANOVA with the Bonferroni adjustment. Statistical analyses were performed with SPSS 10.0 (SPSS, Chicago, IL), and significance was set at P 
0.05.
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RESULTS |
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Subjects exercised at an average work rate of 121 ± 5 W during the Con and LC trials (Table 1). Heart rate was increased during exercise but was not different at rest or exercise between LC and Con.
During rest, LC resulted in initially rapid and subsequently slowed increases in plasma (Fig. 1 and Table 2), whole blood, and erythrocyte [Lac–] (Table 2). During LC, plasma [Lac–] at rest reached 4.2 meq/l, whereas exercise values peaked at 5.7 meq/l. The plasma [Lac–] during exercise approximated those seen during exercise at 65% O2 peak in our previous study (30).
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During rest, there were no significant differences in O2 and CO2 between LC and Con trials (Table 1). However, during exercise, LC resulted in a higher O2 compared with Con. The E responses were not different during rest but were lower during exercise with LC compared with Con. Consequently, E/O2 and E/CO2 were lower during exercise with LC compared with Con. There were no differences in RER at rest and during exercise.
Blood, Plasma, and Erythrocyte Volumes
Hct and Hb were not different between groups or over time (Table 3). [PP] was not different between groups, although [PP] was decreased by the end of the resting period with LC and increased at the onset of exercise in Con (Table 3). During the first 20 min of LC rest, BV and PV tended to decrease, and this was then followed by increases in BV and PV by 60 min (Fig. 2, A and B). The changes were accompanied by a 3 + 1% increase in EV at 30 min that resolved by 90 min (Fig. 2C). The 5% increase in PV at 90 min of LC rest, assuming equilibrium among ECF compartments, represents a 5% (800 ml) increased total ECF volume. This is double the total volume infused during the 90-min rest period. The first 10 min of exercise resulted in rapid and pronounced decreases in BV and PV, with no change in EV (Fig. 2). This was followed by complete restoration of PV and BV during the remainder of the LC exercise period. In contrast, during Con exercise, there was minimal recovery of BV and only partial recovery of PV.
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During rest, LC resulted in a decrease in plasma [K+] (Table 2). The increase in plasma [SID] during LC was mainly due to increased plasma [Na+]. At the onset of exercise, arterial plasma [SID] was increased compared with Con, and this difference widened during exercise (Fig. 3A). With exercise, in the Con trial there was no change in [Na+] (Table 2), whereas during LC, exercise [Na+] continued to increase while [Cl–] was significantly decreased compared with Con. The exercise-induced increase in plasma [K+] was greater in Con than LC (Table 2) and, with respect to [SID], was numerically offset by simultaneous increases in plasma [Lac–] (Fig. 1).
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Whole blood and erythrocyte [SID] were increased with LC (both rest and exercise) compared with Con (Table 2). Erythrocyte [Cl–] decreased by 12–15 meq/l in both trials, but the 3 meq/l greater decrease in LC than Con more than offset the 2–3 meq/l increase in erythrocyte [Lac–] (Table 2). Erythrocyte [Na+] and [K+] remained unchanged during rest and exercise in both trials.
PCO2
During rest, plasma PCO2 was similar between treatments and did not change over time. During exercise, PCO2 was greater in LC than Con (Fig. 3B), although it did not differ from time 0.
Total Weak Acid Concentration
Plasma [Atot] decreased during LC rest (Fig. 3C). Exercise resulted in abrupt increases in [Atot] of similar magnitude in both trials.
Dependent Variables
Measured arterial plasma [H+] decreased over time and approached a significant decrease from time 0 (P = 0.08) by the last sample. Throughout exercise, [H+] was decreased in LC compared with Con (Fig. 4A). In contrast, in the Con trial, [H+] remained unchanged during both rest and exercise. During LC, the increased plasma [SID] was the primary contributor to the decrease in [H+] (Fig. 4B), whereas the decreased [Atot] (compared with Con) also contributed to the alkalosis (Fig. 4D). Changes in PCO2 had no effect on [H+] (Fig. 4C).
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DISCUSSION |
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TOPABSTRACTMATERIALS AND METHODSRESULTSDISCUSSIONGRANTSACKNOWLEDGMENTSREFERENCES |
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CO2 with a concomitant increase in CO2 storage (29, 30) during LC. Our main findings were that 1) the infusion of the hypertonic sodium-lactate solution caused cellular and extracellular volume shifts; 2) with sodium-lactate infusion, both during rest and exercise, plasma [H+] decreased and [HCO3–] increased over time primarily due to increased [SID] and secondarily to decreased [Atot]; and 3) the CO2 and PCO2 responses indicate that respiratory compensation was minimal and did not counter the mild alkalosis that occurred in response to sodium-lactate infusion. Volume Responses in Plasma and Erythrocytes
Plasma and erythrocyte ion concentrations are a function of the water content of these two blood compartments and the net flux of water among extracellular and intracellular compartments. The study was designed so that the rates of infusion and total volumes of solution infused in the Con and LC trials were identical. Therefore, differences in volume responses between the two trials can be attributed to the LC ionic composition and osmolarity (1,300 mosmol/kgH2O) compared with Con (308 mosmol/kgH2O), and the responses of cells to increased extracellular osmolality, [Na+], and [Lac–], particularly at the site of infusion. Erythrocytes passing the infusion site would be exposed to a sharp increase in plasma osmolarity; this, together with sharply increased plasma [Lac–] and [H+] would activate mechanisms for regulating erythrocyte volume and ion balance. During LC, the total amount of Na+ infused during 180 min of rest and exercise averaged 502 meq, which, if retained in and evenly distributed throughout 16.8 liters of ECF, would have raised ECF [Na+] by 30 meq/l; plasma osmolarity would similarly have increased. Clearly, the infusion rate was sufficiently slow to allow for the renal and cellular clearance of 67% of the infused Na+. Furthermore, during 90 min of LC rest, the 380 ml of solution infused represented only 50% of the ECF volume expansion, suggesting net loss of fluid from cells into the extracellular compartments in response to increased extracellular osmolality (27).
During LC at rest, PV increased, plasma [Lac–] and [H+] increased, plasma [K+] and [HCO3–] decreased, whereas plasma [Cl–] remained unchanged. The increased plasma [Na+] and [Lac–] (and osmolality) were due to the infusate composition. Within the erythrocyte compartment, EV was transiently increased at 30 min, [Lac–] increased, and [Cl–] decreased, whereas [Na+] and [K+] remained unchanged; small changes in the concentrations of the latter two ions would not be detectable due to their relatively high concentrations. Erythrocyte [H+] and [HCO3–] could not be determined using the present techniques.
Increased extracellular osmolality results in rapid cellular volume changes and regulatory responses in both erythrocytes (22, 31) and skeletal muscle (13, 23). The initial cellular response is a net loss of fluid and cellular shrinkage, consistent with the observed increase in PV. Within the cells, shrinkage elicits a regulatory volume increase (RVI) driven by increased activity of an inwardly directed NKCC with concomitant increase in Na+-K+-ATPase activity to maintain favorable transmembrane Na+ and Cl– gradients (31). It is likely that an initial erythrocyte shrinkage occurred and was completed within the first 10 min of the infusion (22). It may be that the later transient increase in EV (increased at 30 min of rest) resulted from increased osmotic water flux associated with increased erythrocyte [Lac–] and possibly partially due to an overshoot in the RVI response. The decrease in plasma [K+] during resting LC is consistent with expansion of the ECF volume and increased activities of the NKCC and Na+-K+-ATPase. Corresponding changes in plasma and erythrocyte concentrations of Na+ and Cl– would be masked by their relatively large concentrations.
The reason(s) for the decrease in erythrocyte [Cl–] during both rest and exercise with LC may be related to activation of regulatory volume-decreasing mechanisms. This net loss of Cl– from cells, in the face of unchanged plasma [Cl–], also suggests an increased clearance of Cl– from the vascular compartment by other cells or by the kidneys, in addition to the net exchange of extracellular weak anion (HCO3– or OH–) for erythrocyte Cl–. At the level of the erythrocyte, an HCO3–/Cl– exchange could be affected by band-3 protein, and this is reasonable given the progressive increases in plasma [HCO3–] and decreases in [H+] as exercise continued (14).
A net loss of cellular Cl– has also been seen from muscle perfused with elevated (11 meq/l) plasma [Lac–], although in those experiments plasma was acidic with [H+] 71 neq/l and [HCO3–] 9.2 meq/l (6). Those and the present results can be interpreted to mean that a lactate/chloride exchange by band-3 protein across the cell membrane favors cellular Cl– loss when plasma [Lac–] is elevated (32, 42). It is possible that there was an increased fractional excretion of Cl– by the kidneys in response to hypertonic LC, but this does not appear to have been characterized in the experimental or clinical literature.
There is also evidence in support of increased renal Cl– excretion in response to Na+ loading. In the present study, during 180 min of LC, 67% of infused Na+ was cleared from the ECF compartment. In contrast to rapid and effective Lac– removal/oxidation mechanisms (see below), removal of infused [Na+] is primarily the responsibility of the kidneys, subject to hypothalamic-pituitary regulation and relatively slow onset (20). The renal response for removal of excess extracellular Na+ is an increased excretion of Cl– (20). From the observed maintenance of plasma [Cl–] and the progressive decrease in erythrocyte [Cl–] during LC, it appears that plasma [Cl–] was well regulated, but we suggest that this occurred at the expense of intracellular Cl– to balance increased renal Cl– excretion.
The time course and magnitude of plasma, erythrocyte, and muscle volumes in response to moderate-intensity exercise have been characterized (27) and warrants further comment only with respect to LC. PV recovered more rapidly and to a greater extent in LC than in Con, and this may be attributed to already increased activities of the NKCC and Na+-K+-ATPase in the face of increased plasma osmolality.
Acid-Base Responses
During Con, changes in independent plasma acid-base variables during rest and exercise were small and effectively cancelled each other such that there were no changes in dependent acid-base variables over time. In the LC trials, both during rest and exercise, the infusion resulted in increased plasma [Na+], which was the main contributor to increased plasma [SID], as the increased [Lac–] would reduce [SID]. During LC, with respect to the quantitative contribution of independent variables to the decreases in plasma [H+] and increases in [HCO3–], it was the increase in plasma [Na+] (and hence [SID]) that was primarily responsible. The elevated osmolality of the infusate resulted in an increase in PV, and hence plasma [Atot] decreased; this was the secondary contributor to decreased [H+] and increased [HCO3–]. There was minimal effect of plasma PCO2 on dependent acid-base variables. Therefore, under these conditions, the acid-base disturbance was caused by the infusion and extracellular accumulation of strong base cation (plasma Na+), by a decrease in the concentration of extracellular weak acid anions (plasma proteins), and from cellular Lac– (strong acid anion) removal.
The indirect contribution of Lac– removal to the observed progressive increase in plasma [SID] during rest and exercise in LC warrants further consideration. The net extraction and oxidation of Lac– by cells throughout the body (29, 30, 38) effectively reduces plasma [Lac–] while leaving [Na+] relatively unchanged (Ref. 6; Table 2). On average, the total amount of Lac– infused during 90 min of rest was 240 mmol, which would have raised plasma [Lac–] from 1 to 49 meq/l if all of the infused Lac– was distributed evenly within the 5 liters of total blood volume. However, peak plasma and erythrocyte [Lac–] were 4.1 and 3.3 meq/l, respectively, indicating that 44 mmol (92%) of the infused Lac– was removed from the vascular compartment during the 90-min resting period. With an average lactate distribution volume of 53 liters (0.64 x body mass), steady-state plasma [Lac–] would have been increased by 4.5 meq/l. However, plasma [Lac–] during the resting period increased by 3 meq/l, suggesting conversion to other metabolites (e.g., increased contribution to gluconeogenesis) and oxidation. This effective removal of circulating Lac– continued during the exercise period, with virtually all of the 274 mmol of Lac– infused during 90 min of exercise removed. Clearly, an inability to effectively remove circulating Lac– would have resulted in pronounced decreases in plasma [SID] with concomitant large increases in [H+] and decreases in [HCO3–].
PCO2 and Ventilatory Contributions to Plasma Acid-Base Regulation and HCO3– Dynamics
During exercise with LC, O2 was increased compared with Con. It was reported that, during rest, LC results in an increased O2 presumably due to the energetic cost of gluconeogenesis from Lac– (40) or glycogen synthesis (10). The present study can neither confirm nor discount these possibilities. However, we speculate that there is an increased requirement for cellular Na+/K+ pumping during LC and that increased Na+-K+-ATPase activity may at least partially contribute to the increased O2 (41).
The decrease in E in response to LC is similar to that seen previously (40) and may be explained by decreased peripheral chemoreceptor drive in response to lowered plasma [H+] (36), although this decrease was <10 meq/l, or increased plasma osmolality (1). Others reported that sodium-acetate infusion increased [HCO3–], and the increased [HCO3–] was followed by increased urinary HCO3– excretion (5). Therefore, in the present study, although some CO2 could have escaped pulmonary excretion, the decreased E was adequate to sustain an increased O2 and maintain PCO2 constant. Thus during Con and LC, PCO2 had little effect on acid-base status.
CO2 storage during the LC trial could contribute to pulmonary RER underestimating the cell respiratory quotient. Because, in the present study, the infused Na+ remained extracellular or was cleared (see above) and most of the Lac– that enters the cell was removed, there was likely no significant increase in intracellular CO2 storage. During LC rest, ECF volume expanded by 800 ml from 16-liter preinfusion, thus the 3.5 meq/l increase in plasma [HCO3–] represents a 58 mmol (12%) increase in extracellular CO2 storage; an additional 50 mmol was added during 90 min of LC exercise. The rate of extracellular CO2 storage at rest equates to 0.007 l/min, which if added to CO2, would increase RER from 0.79 (Table 1) to 0.82, suggesting a higher rate of carbohydrate metabolism than that estimated from gas-exchange measurements. With exercise, however, the additional increase in CO2 storage is negligible compared with the high rates of cellular CO2 production and would not affect the RER and the estimation of substrate oxidation.
Lactate Infusate
As previously discussed (29), the pH of the infusate (4.8) was selected because it represented the best compromise between subject comfort and excess Na+ load. In a previous study on dogs by Gladden and Yates (12), it was demonstrated that lactate infusates between pH 3.4 and 7.0 had the least impact on arterial pH. Although an infusate pH of 3.4 to 4.0 left blood pH unchanged, infusion of a mixture this acidic is impractical in human subjects due to local irritation at the infusion site. Conversely, a mixture containing a pH greater than the one chosen would introduce a substantial quantity of Na+ into the participant. Therefore, it was important for us to clarify the effects of the chosen infusate because we believe that it represents a means to maximize [Lac–] while minimizing [Na+].
Acid-Base and Metabolic Perspectives
Lactate is unique among the strong ions because it is organic, highly permeant to cell membranes, and readily oxidized. Although the inorganic strong ions can be considered in terms of cellular transport, intracellular and extracellular [Lac–] are functions of production, transport, and oxidation. Lactate production, transport, and removal all play integral roles in the regulation of cellular, extracellular, and whole body acid-base balance (6, 17, 34). Lactate shuttling and oxidation occurs both between (2) and within (4) skeletal muscle and is facilitated by the distribution of Lac– through the body by erythrocytes (26). Additionally, it has been demonstrated that when plasma [Lac–] is elevated, Lac– is a preferred carbohydrate substrate by skeletal muscle at rest (7) and during moderate-intensity exercise (29, 30). The high rates of skeletal muscle Lac– removal and oxidation under these conditions clearly plays an important role in decreasing the extracellular acidification that would occur if Lac– was allowed to accumulate. When viewed in this context, cellular energy metabolism (of lactate specifically) is the primary mechanism for regulation of extracellular acid-base balance compared with mechanisms that regulate extracellular inorganic ion concentrations.
In summary, sodium-lactate infusions have been used as a clinical intervention and to reveal the role of lactate as a metabolic intermediate. However, the introduction of hypertonic solutions containing the strong ions sodium and lactate causes rapid fluid and acid-base changes. On the whole, compared with exercise-induced ion, volume, and acid-base changes, the changes induced by hypertonic sodium-lactate solutions in resting subjects are modest at best. The increase in extracellular CO2 storage has only a minor effect on measured RER at rest and no effect during exercise, so its effects on the measurement of substrate partitioning can be ignored. Although changes in respiratory parameters must be taken into consideration, the clamp technique is appropriate for studies of lactate flux and lactate-glucose interactions.
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TOPABSTRACTMATERIALS AND METHODSRESULTSDISCUSSIONGRANTSACKNOWLEDGMENTSREFERENCES |
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ACKNOWLEDGMENTS |
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TOPABSTRACTMATERIALS AND METHODSRESULTSDISCUSSIONGRANTSACKNOWLEDGMENTSREFERENCES |
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FOOTNOTES |
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The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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, LC; 
, control trial (Con). #Significantly different from Con (P < 0.05). 
Significantly different from LC time 0 (P < 0.05).
