Academic literature on the topic 'Dialysate pH'

We determined the activity of noradrenergic neurons in the nucleus of the posterior hypothalamus (PH) of sinoaortic-denervated (SAD) and sham-operated (SO) rats during cardiovascular responses to intravenous (iv) or local brain dialysis of NaCl. PH extracellular norepinephrine (NE) was collected by microdialysis from freely moving rats, and dialysate NE was measured by radioenzymatic assay. Three days after SAD or SO, mean arterial pressure (MAP) and heart rate (HR) were significantly higher in SAD rats than SO rats. Basal levels of PH dialysate were also significantly elevated in SAD rats. Local dialysis of PH with hypertonic NaCl produced pressor and tachycardiac responses coupled with increased NE release in PH in both groups, but the increases in MAP and dialysate NE were larger in SAD than SO rats. Ganglionic blockade with iv hexamethonium elicited significantly larger depressor and bradycardiac responses in SAD rats, whereas the percent increase of dialysate NE was smaller than that of SO rats. The iv infusion of hypertonic NaCl produced larger pressor responses in SAD than SO rats and a significant increase in dialysate NE from PH of SAD but not SO rats. These findings indicate that 1) PH is an important site of NaCl action and 2) noradrenergic input in PH receives tonic inhibitory input from baroreflex pathways and contributes to cardiovascular hyperactivity and hypertension in SAD rats.

Uremic acidosis accompanies chronic renal failure in hemodialysis patients because of a retention of nonvolatile acids. Standard bicarbonate (39 mEq/L) and acetate (38 mEq/L) dialysates do not completely correct the acidosis. The acid-base and biochemical effect of a high-bicarbonate (42 mEq/L) dialysate was evaluated in 38 patients during high-efficiency and high-flux dialysis over 12 wk. All patients were dialyzed on standard bicarbonate dialysate before the study and for 8 wk after the study. In order to monitor potential excessive alkalosis, predialysis and postdialysis arterial blood gases were measured in seven patients who initially had a normal predialysis pH. Serum chemistries revealed no significant changes in predialysis BUN, calcium, ionized calcium, or phosphorus during the 12-wk study. There was no change in postdialysis ionized calcium or phosphorus. Predialysis and postdialysis serum total CO2 (STCO2) increased over the 12-wk study (P < 0.0001). By week 12, 75% of the hemodialysis patients had an STCO2 > 23 mEq/L and no patient had an STCO2 > 30 mEq/L predialysis. After the 8-wk washout, all chemistries were no different from prestudy concentrations. Predialysis blood gases in seven patients with normal predialysis HCO3 revealed a significant increase (P < 0.009) in PCO2 and HCO3 over the 12-wk study; predialysis pH and PO2 did not change. There was no significant change in postdialysis blood gases. It was concluded that: (1) a high-bicarbonate dialysate corrects predialysis acidosis in 75% of hemodialysis patients without causing progressive alkalemia, hypoxia, or hypercarbia; and (2) predialysis BUN, calcium, ionized calcium, and phosphorus are unaffected by high-bicarbonate dialysate.

Poisoning is a significant cause of injury-related death worldwide. Dialysis is usually ineffective in removing the toxin once it has been absorbed because of drug protein binding and high volumes of distribution. In this work, we explore whether the addition of liposomes to peritoneal dialysate could extract protein bound amitriptyline. Liposomes were prepared using the thin film hydration method. In the in vitro experiment, 3 mL of 20% albumin with a concentration of 6000 nmol/L amitriptyline in a proprietary dialysis cartridge was dialysed against 125 mL of phosphate-buffered saline with and without 80 mg 1,2-dioleoyl-sn-glycero-3-phosphoglycerol (DOPG) liposomes. In the in vivo arm, peritoneal dialysis was undertaken in 6 rats with pH gradient liposome augmented dialysate after intravenous amitriptyline injection. Peritoneal blood flow was estimated by CO2 extraction. Total amitriptyline extracted was compared to freely dissolved (non-protein bound) and total amitriptyline perfusing the membrane during the peritoneal dwell. Mean liposome size for DOPG and acidic centre pH gradient liposomes was 119 nm and 430 nm, respectively. In the in vitro experiment, more amitriptyline was extracted into the liposome containing dialysate than the control dialysate (40 +/− 2 nmol/L vs. 27 +/− 1 nmol/L). In the in vivo experiment, the total amitriptyline in dialysate was 5240 +/− 2750 nmol. Mean total free amitriptyline perfusing the peritoneal membrane was 93 +/− 46 nmol. Mean total blood amitriptyline perfusing the peritoneal membrane was 23,920 +/− 6920 nmol. Two of the six animals were excluded due to overestimation of peritoneal blood flow. This exploratory work suggests the addition of liposome nanoparticles to peritoneal dialysate extracted protein bound amitriptyline from blood.

Objective To assess the in vivo peritoneal inflammatory reaction in rats dialyzed with neutral, bicarbonatelactate-buffered dialysis fluid. Methods Chronic peritoneal dialysis was performed for 4 weeks in Wistar rats with two solutions: (1) 40 mmol/l lactate-buffered fluid, pH 5.2, with a glucose concentration of 2.27 gldl (lac); and, (2) 15 mmolll lactate and 25 mmolll bicarbonate-buffered fluid, pH 7.0 -7.5, with a glucose concentration of 2.27gldl (Bic-lac). After 4 weeks, two peritoneal equilibration tests (PET 1 and PET 2) were performed in all animals with each respective solution. PET 1 was done with test solutions alone, whereas, on a subsequent day, PET 2 was performed with test solutions supplemented with endotoxin [lipopolysaccharide (IPS)] to induce peritonitis. Results During PET 1 no consistent differences were detected in peritoneal permeability between the lac and Bic-lac groups. Total dialysate cell count in the Bic-lac animals was lower than in rats treated with lac fluid: that is, at 8 hours, the respective counts were 1858 ± 524 cellslμl versus 2785 ± 1162 cellslμl (p < 0.01). Dialysate from animals dialyzed with Bic-lac contained more macrophages (at 4 hours: 53.6% ± 35.8% versus 35.8% ± 8.8%, p < 0.001) and fewer neutrophils (at 4 hours: 3.6% ± 1.8% versus 15.4%± 6.1%, p < 0.001) as compared to those dialyzed with the lac solution. Concentration of nitrites in 8-hour dwell dialysate samples from Bic-lac rats was lower than that in the lac group (0.98 ± 0.28 μmollml versus 2.32 ± 0.87 μmollml, p < 0.002), but cytokine levels in the dialysates were comparable. During PET 2, the in -crease in peritoneal permeability resulting from the lPS induced inflammatory response was similar for both test solutions. Dialysate cell count was higher in the lac group versus the Bic-lac group (at 8 hours: 8789 ± 4862 cellslμl versus 3961 ± 581 cellslμl, p < 0.001), contained more neutrophils (at 8 hours: 80.0% ± 11.3% versus 54.8% ± 4.4%, p < 0.001) and fewer macrophages (at 8 hours: 6.8% ± 5.6% versus 21.2% ± 3.3%, p < 0.05). During peritonitis, we found a higher overall dialysate concentration of both tumor necrosis factor (TNFα: +53%, p < 0.05) and of interferon gamma (lFN-y: +303%, p < 0.02), in the Bic-lac group than in the lac group. Conclusions A lower dialysate cell count, higher percentage of macrophages, and lower percentage of neutrophils in dialysate suggest that Bic-lac fluid induces a diminished nonspecific inflammatory response of the peritoneal cavity during dialysis. However, after in vivo stimulation, peritoneal cells from animals dialyzed with Bic-lac solution possess an augmented ability to produce inflammatory cytokines.

The major objective of this study was to compare the magnitude and duration of cardiovascular (CV) responses to acute environmental stresses with the associated patterns of noradrenergic activity in the paraventricular nucleus (PVN) and posterior nucleus (PH) of the hypothalamus. Simultaneous microdialysis samples of extracellular norepinephrine (NE) were collected at 5-min intervals from PVN and PH and the CV responses were recorded before, during, and for 15 min after acute shaker (cage oscillation) stress or inhalation of ether vapor in freely moving rats. Five minutes of shaker stress, 60 and 150 cycles/min, elicited pressor responses coupled with increases in dialysate NE from both PVN and PH in a frequency-dependent manner. Tachycardia occurred at 150 but not 60 cycles/min. Ten minutes after 60 cycles/min and 15 min after 150 cycles/min, NE efflux in PH was still increased, whereas in PVN it returned to control as had arterial pressure and heart rate. Ether vapor elicited a transient CV response but a continuing efflux of NE in PH and PVN. Urethan anesthesia raised baseline values of dialysate NE in PH and PVN but significantly attenuated cardiovascular and dialysate NE responses to shaker stress. We conclude that acute environmental stress simultaneously elicits CV responses and the efflux of NE from PVN and PH but, during or after stress, CV values may return to control levels while NE efflux remains elevated in PVN and/or PH.

The soluble phase of milk was separated at 20 and 80°C using ultrafiltration. The resulting permeates were then subjected to further ultrafiltration and dialysis at close to these two temperatures. It was found that pH, Ca2+ and soluble Ca decreased as the separation temperature increased both in original UF permeates and in dialysates obtained from these permeates, but P decreased only slightly. The major reason for these changes was due to the precipitation of calcium phosphate/citrate complexes onto the casein micelle with concomitant release of H+. The pH of both permeates and dialysates from milk at 20°C were slightly higher than for milk. When UF permeates collected at 20 and 80°C, were each dialysed at both these temperatures, the dialysate collected at 80°C showed much less temperature dependence for pH and ionic calcium compared with that collected at 20°C. This is in contrast to milk, which shows considerable temperature dependence for pH and ionic calcium. Further experiments revealed that the pH and Ca2+ concentration of permeates showed high temperature dependence above the temperature at which they were separated, but a much lower temperature dependence below that temperature. These findings suggest that dialysis and UF of milk at high temperature provide the best means yet for estimating the pH and ionic calcium of milk at that temperature.

Background: Extracorporeal carbon dioxide removal may be used to manage hypercapnia, but compared to dialysis, it’s not widely available. A recent in vitro study showed that dialysis with low bicarbonate dialysates removes CO2. Objective: To show that bicarbonate dialysis removes CO2 in an animal model to validate in-vitro findings and quantify the effect on arterial pH. Methods: Male Sprague-Dawley hypercapnic rats were dialyzed with either a conventional dialysate (PrismasolTM) or a bicarbonate-free dialysate (Bicarb0). The effect of dialysis on standard blood gases and electrolytes was measured. Results: Partial pressure of CO2 and bicarbonate concentration in blood decreased significantly after exposure to Bicarb0 compared to PrismasolTM (filter outflow values 12.8 vs 81.1 mmHg; p < 0.01 for CO2 and 3.5 vs 22.0 mmol/L; p < 0.01 for bicarbonate). Total CO2 content of blood was reduced by 459 mL/L during dialysis with Bicarb0 (filter inflow 546 ± 91 vs filter outflow 87 ± 52 mL/L; p < 0.01), but was not significantly reduced with PrismasolTM. Conclusions: Bicarbonate dialysis removes CO2 at rates comparable to existing low-flow ECCO2R.

Objective To investigate the possible effects of different concentrations of ionized sodium (NaI) on peritoneal ultrafiltration (UF) rate using lactate (Lac) and lactate/bicarbonate (Lac/Bic) dialysis solutions. Design Two random consecutive (after an interval of 48 hours) peritoneal equilibration tests (PETs) were performed in 13 patients (4 males and 9 females) on regular continuous ambulatory peritoneal dialysis (PD) treatment for at least 3 months. Two different PD solutions containing anhydrous glucose 3.86% were used: a 40 mmol/L Lac solution and a 15/25 mmol/L mixed Lac/Bic solution. Concentrations of total sodium (NaT) and NaI were measured by flame photometer and direct ion-selective electrode respectively. Results Dialysate concentrations of NaT were not different during PETs using Lac and Lac/Bic. Dialysate concentrations of NaI in fresh PD solutions were different (133.3 ± 1.7 vs 128.2 ± 3.9 mmol, p < 0.0001); however, these differences disappeared just after the end of the infusion of the fresh solutions. Peritoneal UF rate was not significantly different during PETs using Lac versus Lac/Bic (609 ± 301 mL vs 542 ± 362 mL). The dialysate-to-plasma ratios of sodium concentrations at 60 minutes of the PETs (which are expressions of free water transport) were not different using Lac versus Lac/Bic (0.89 ± 0.04 vs 0.89 ± 0.04 respectively, p = 0.96). All the other classical parameters of the PET were not different between Lac and Lac/Bic. Conclusions The higher dialysate concentrations of NaI due to lower dialysate pH and consequently the higher effective osmolality of the fresh Lac PD solutions did not influence peritoneal UF rate, probably because of the fast reduction of NaI concentrations due to rapid correction of dialysate pH at the end of the infusion of Lac solutions into the peritoneal cavity.

Objective To study the effect of dialysis fluid on the release of interleukin-1β (IL-1β) and tumor necrosis factor (TNFα) by peritoneal macrophages (PM) and peripheral blood mononuclear cells (MNC), and the time course and factors involved in this effect Design PM and MNC were incubated for various periods with Dianeal itself, or Dianeal of varying pH and composition.IL-1 β was measured by radioimmunoassay and TNFα by cytotoxicity assay. Patients PM were obtained by centrifugation of dialysis effluent from 3 continuous ambulatory peritoneal dialysis (CAPD) patients. MNC were obtained from healthy volunteers. Results Dialysis fluid inhibited the release of both cytokines. Indomethacin had no effect on the inhibition of TNFα release caused by dialysis fluid. Thus prostaglandins are not involved in this inhibition. Solutions of pH 5.2 and high lactate concentration caused an identical inhibition to that caused by dialysate, whereas the presence or absence of glucose had no effect. Thus it seems that pH and lactate are the important inhibitory factors. Time course studies showed that the inhibition of TNFα release was substantial after only 15 minutes of incubation with dialysate, whereas the inhibition of IL-1 β became significant only after 60 minutes of incubation. Conclusions Even though dialysate pH rises within 15–30 minutes after instillation into the abdomen, the initial low pH present for only a short time could have a significant effect on TNFα release by peritoneal macrophages, and thus on their ability to mount a normal inflammatory response. Lactate also has a significant inhibitory role. It is suggested that commercial dialysis solutions should have a pH of 7. Oandthata physiological buffer other than lactate be used.

BackgroundThe use of amino acid (AA) dialysate to ameliorate protein-energy malnutrition has been limited by adverse metabolic effects.ObjectiveWe undertook this study to examine the acute metabolic effects of escalating doses of AAs delivered with lactate/bicarbonate dialysate on automated peritoneal dialysis (APD).Patients and Methods12 APD patients were treated with conventional lactate-buffered dialysate (week 1), followed by lactate/bicarbonate-buffered dialysate (week 2), then 2 – 2.5 L 1.1% AA solution were added (week 3), and then an additional 2 – 2.5 L 1.1% AA were added (week 4). The primary outcomes were change in serum bicarbonate and pH, change in protein catabolic rate (PCR), and change in normalized ultrafiltration (milliliters/gram of carbohydrate infused).ResultsSerum bicarbonate rose from week 1 to week 2 (28.9 ± 3.2 vs 26.9 ± 4.1 mmol/L, p = 0.03). Addition of one bag of AAs led to a decline in plasma bicarbonate (26.9 ± 2.1 vs 28.9 ± 3.2 mmol/L, p < 0.01), which was further magnified by the addition of the second bag of AAs (23.8 ± 2.7 vs 26.9 ± 2.1 mmol/L, p < 0.01). Serum bicarbonate fell significantly by week 4 compared to week 1 (23.8 ± 2.7 vs 26.9 ± 3.2 mmol/L, p < 0.01) although there was no significant change in venous pH or PCR when week 4 was compared to week 1. Normalized ultrafiltration was stable for the first 3 weeks but rose significantly in week 4 compared to week 1 (5.32 ± 2.30 vs 4.14 ± 1.58 mL/g, p = 0.03).ConclusionsHigher doses of AAs mixed with newer bicarbonate/lactate dialysate on APD result in a small decrease in serum bicarbonate but improved normalized ultrafiltration. This merits further study as both a nutritional supplement and a glucose-sparing strategy.

The aims of this thesis were to: 1) develop a new method for the determination of interstitial pH at rest and during exercise in vivo, 2) systematically explore the effects of different ingestion regimes of 300 mg.kg-1 sodium citrate on blood and urine pH at rest, and 3) to combine the new interstitial pH technique with the findings of the second investigation in an attempt to provide a greater understanding of H+ movement between the extracellular compartments. The purpose of the first study was to develop a method for the continuous measurement of interstitial pH in vastus lateralis was successfully developed using microdialysis and 2,7-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein (BCECF). To avoid the presence of an artificial alkalosis during exercise, it was necessary to add 25 mM HCO3- to the perfusate. The outlet of the probe was cut less than 10 mm from the skin and connected to a stainless steel tube completing the circuit to a microflow-through cuvette (8 fÝl) within a fluorescence spectrophotometer. This prevented the loss of carbon dioxide from the dialysate and any subsequent pH artefact. Interstitial pH was collected from six subjects before, during and after five minutes of knee-extensor exercise at three intensities 30, 50, and 70 W. Mean,,bSEM interstitial pH at rest was 7.38,,b0.02. Exercise reduced interstitial pH in an almost linear fashion. The nadir value for interstitial pH at 30, 50 and 70 W exercise was 7.27, 7.16 and 7.04, respectively. The lowest pH was obtained 1 min after exercise, irrespective of workload, after which the interstitial pH recovered in a nearly exponential manner. The mean half time of interstitial recovery was 5.2 min. The changes in interstitial pH exceeded the changes in venous blood pH. This study demonstrated that interstitial pH can be measured using microdialysis and that it is continuously decreased during muscle activity. The purpose of the second study was to establish an optimal ingestion regime for the ingestion of 300 mg.kg-1 of sodium citrate and maximise the alkalotic effect while minimising any side effects. Increasing the effectiveness of alkali ingestion may lead to further increases in muscle performance. Ingesting 300 mg.kg-1 sodium citrate at a rate of 300 mg.min-1 was identified as the optimal ingestion regime to maximise alkalosis at rest, which occurred 3.5 h post-ingestion. This was determined by monitoring eight human subjects ingesting 300 mg.kg-1 sodium citrate at five different rates, control (no ingestant), bolus, 300, 600 and 900 mg.kg.min-1 on five days separated by at least 48 hours. Sodium citrate was ingested in capsule form with water ad libitum, with the exception of bolus, which was combined with 400 ml less than 25 percent orange juice and consumed in less than 1 min. Arterialised blood (mean 71.3,,b3.5 mmHg) acid-base and electrolyte status was assessed via the withdrawal of ~5 ml of blood every 30 min across an eight hour duration, placed on ice and analysed within five minutes. No alkalotic difference was found between ingestion rates (mean 7.445,,b0.004, 7.438,,b0.004 and 7.442,,b0.004 for 300, 600 and 900 mg.min-1, respectively). All experimental ingestion regimes were associated with elevations in [HCO3-] (29.6, 29.7, 29.8, 29.9 and 26.3 mmol.l-1 for bolus, 300, 600, 900 and control, respectively). The 300 ingestion regime had the greatest impact on [H+], a 0.66 meq.l-1,,e10-8 change. Bolus ingestion (3.93,,b0.08 mmol.l-1) of sodium citrate had no effect on control (4.06,,b0.08 mmol.l-1) blood [K+], however, 300 mg.min-1 decreased blood [K+] (p less than 0.05). There was no effect of sodium citrate on blood [Cl-], but after 2.5 h blood [Cl-] was lower than pre-ingestion values (p less than0.05). All ingestion rates of sodium citrate increased (p less than 0.05) urine pH above control. This is the first study to investigate the effect of varying ingestion rates on acid-base status at rest in humans. The results suggest that ingesting sodium citrate in small doses in quick succession induce a greater blood alkalosis than the commonly practised bolus protocol. Using the interstitial pH technique described above and the optimal ingestion regime (300 mg.min-1) identified above, the final experiment was designed to assess the influence of sodium citrate ingestion on interstitial pH at both rest and during exercise. Five subjects ingested 300 mg.kg-1 sodium citrate at 300 mg.min-1 again in capsule form with water ad libitum. Prior to ingestion, each subject had a cannula placed into their cephalic vein and one microdialysis probe (CMA-60) inserted into their left thigh, orientated along the fibres of vastus lateralus. This probe was used for the measurement of pH as described above. At the end of this period, an exercise protocol required five subjects to perform light exercise (10 W) for 10 min, before starting an intense exercise period (~90-95% leg VO2peak) to exhaustion followed by a 15 min recovery period. Dialysate and blood samples were collected across all periods. Mean,,bSEM interstitial pH for placebo and alkalosis were 7.38,,b0.12 and 7.24,,b0.16, respectively. Sodium citrate ingestion was not associated with an interstitial alkalosis. An exercise induced acidosis was observed in the interstitium during placebo but not during alkalosis (p less than 0.05). Mean,,bSEM venous pH were 7.362,,b0.003 and 7.398,,b0.003 for placebo and alkalosis, respectively. Sodium citrate ingestion was not associated with a venous alkalosis. Sodium citrate ingestion was associated with an increase in mean,,bSEM venous [HCO3-] (placebo 25.5,,b0.2, alkalosis 28.1,,b0.2). This increase in the blood bicarbonate buffer system was not associated with an increase in time to exhaustion (placebo 352,,b71, alkalosis 415,,b171). This was the first study to investigate the effects of sodium citrate ingestion on interstitial pH. The results of this study demonstrated that an interstitial alkalosis does not ensue after alkali ingestion, however, it was associated with the lack of an exercise induced acidosis suggesting an improved pH regulation during exercise.

The aims of this thesis were to: 1) develop a new method for the determination of interstitial pH at rest and during exercise in vivo, 2) systematically explore the effects of different ingestion regimes of 300 mg.kg-1 sodium citrate on blood and urine pH at rest, and 3) to combine the new interstitial pH technique with the findings of the second investigation in an attempt to provide a greater understanding of H+ movement between the extracellular compartments. The purpose of the first study was to develop a method for the continuous measurement of interstitial pH in vastus lateralis was successfully developed using microdialysis and 2,7-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein (BCECF). To avoid the presence of an artificial alkalosis during exercise, it was necessary to add 25 mM HCO3- to the perfusate. The outlet of the probe was cut less than 10 mm from the skin and connected to a stainless steel tube completing the circuit to a microflow-through cuvette (8 fÝl) within a fluorescence spectrophotometer. This prevented the loss of carbon dioxide from the dialysate and any subsequent pH artefact. Interstitial pH was collected from six subjects before, during and after five minutes of knee-extensor exercise at three intensities 30, 50, and 70 W. Mean,,bSEM interstitial pH at rest was 7.38,,b0.02. Exercise reduced interstitial pH in an almost linear fashion. The nadir value for interstitial pH at 30, 50 and 70 W exercise was 7.27, 7.16 and 7.04, respectively. The lowest pH was obtained 1 min after exercise, irrespective of workload, after which the interstitial pH recovered in a nearly exponential manner. The mean half time of interstitial recovery was 5.2 min. The changes in interstitial pH exceeded the changes in venous blood pH. This study demonstrated that interstitial pH can be measured using microdialysis and that it is continuously decreased during muscle activity. The purpose of the second study was to establish an optimal ingestion regime for the ingestion of 300 mg.kg-1 of sodium citrate and maximise the alkalotic effect while minimising any side effects. Increasing the effectiveness of alkali ingestion may lead to further increases in muscle performance. Ingesting 300 mg.kg-1 sodium citrate at a rate of 300 mg.min-1 was identified as the optimal ingestion regime to maximise alkalosis at rest, which occurred 3.5 h post-ingestion. This was determined by monitoring eight human subjects ingesting 300 mg.kg-1 sodium citrate at five different rates, control (no ingestant), bolus, 300, 600 and 900 mg.kg.min-1 on five days separated by at least 48 hours. Sodium citrate was ingested in capsule form with water ad libitum, with the exception of bolus, which was combined with 400 ml less than 25 percent orange juice and consumed in less than 1 min. Arterialised blood (mean 71.3,,b3.5 mmHg) acid-base and electrolyte status was assessed via the withdrawal of ~5 ml of blood every 30 min across an eight hour duration, placed on ice and analysed within five minutes. No alkalotic difference was found between ingestion rates (mean 7.445,,b0.004, 7.438,,b0.004 and 7.442,,b0.004 for 300, 600 and 900 mg.min-1, respectively). All experimental ingestion regimes were associated with elevations in [HCO3-] (29.6, 29.7, 29.8, 29.9 and 26.3 mmol.l-1 for bolus, 300, 600, 900 and control, respectively). The 300 ingestion regime had the greatest impact on [H+], a 0.66 meq.l-1,,e10-8 change. Bolus ingestion (3.93,,b0.08 mmol.l-1) of sodium citrate had no effect on control (4.06,,b0.08 mmol.l-1) blood [K+], however, 300 mg.min-1 decreased blood [K+] (p less than 0.05). There was no effect of sodium citrate on blood [Cl-], but after 2.5 h blood [Cl-] was lower than pre-ingestion values (p less than0.05). All ingestion rates of sodium citrate increased (p less than 0.05) urine pH above control. This is the first study to investigate the effect of varying ingestion rates on acid-base status at rest in humans. The results suggest that ingesting sodium citrate in small doses in quick succession induce a greater blood alkalosis than the commonly practised bolus protocol. Using the interstitial pH technique described above and the optimal ingestion regime (300 mg.min-1) identified above, the final experiment was designed to assess the influence of sodium citrate ingestion on interstitial pH at both rest and during exercise. Five subjects ingested 300 mg.kg-1 sodium citrate at 300 mg.min-1 again in capsule form with water ad libitum. Prior to ingestion, each subject had a cannula placed into their cephalic vein and one microdialysis probe (CMA-60) inserted into their left thigh, orientated along the fibres of vastus lateralus. This probe was used for the measurement of pH as described above. At the end of this period, an exercise protocol required five subjects to perform light exercise (10 W) for 10 min, before starting an intense exercise period (~90-95% leg VO2peak) to exhaustion followed by a 15 min recovery period. Dialysate and blood samples were collected across all periods. Mean,,bSEM interstitial pH for placebo and alkalosis were 7.38,,b0.12 and 7.24,,b0.16, respectively. Sodium citrate ingestion was not associated with an interstitial alkalosis. An exercise induced acidosis was observed in the interstitium during placebo but not during alkalosis (p less than 0.05). Mean,,bSEM venous pH were 7.362,,b0.003 and 7.398,,b0.003 for placebo and alkalosis, respectively. Sodium citrate ingestion was not associated with a venous alkalosis. Sodium citrate ingestion was associated with an increase in mean,,bSEM venous [HCO3-] (placebo 25.5,,b0.2, alkalosis 28.1,,b0.2). This increase in the blood bicarbonate buffer system was not associated with an increase in time to exhaustion (placebo 352,,b71, alkalosis 415,,b171). This was the first study to investigate the effects of sodium citrate ingestion on interstitial pH. The results of this study demonstrated that an interstitial alkalosis does not ensue after alkali ingestion, however, it was associated with the lack of an exercise induced acidosis suggesting an improved pH regulation during exercise.