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Clinical evaluation of a peritoneal dialysis solution with 33 mmol/L bicarbonate.

OBJECTIVE: To evaluate the efficacy and safety of a new peritoneal dialysis solution with 33 mmol/L bicarbonate. DESIGN: In an acute, prospective, randomized cross-over study, 8 patients were randomized in two groups of 4. On the first study day, the first group performed two consecutive 4-hour exchanges with a dialysis solution containing 35 mmol/L lactate: the first exchange with 13.6 g/L and the second with 38.6 g/L dextrose. On the second study day, the same type of exchanges were performed with bicarbonate. The second group underwent the same treatment, but used bicarbonate solutions on the first day and control solutions on the second study day. Thirty-three patients participated in a 2-month prospective and randomized study. After a 4-week baseline period using solutions containing 40 mmol/L lactate, the patients were dialyzed with either 33 mmol/L bicarbonate solutions or 40 mmol/L lactate solutions. SETTING: Peritoneal dialysis units at the University Hospital of Brescia and the Niguarda Hospital of Milan, Italy. RESULTS: Acute study: Control and bicarbonate solutions had similar effects on blood chemistries and peritoneal transport. Chronic study: Mean venous bicarbonate concentrations remained unchanged in the control group (26.6-27.2 mmol/L), but decreased significantly in the bicarbonate group from 28.8 mmol/L at the start of the study to 23.0 mmol/L after 2 months of bicarbonate administration. Other biochemical parameters remained unchanged. CONCLUSION: A peritoneal dialysis solution with a bicarbonate level of 33 mmol/L does not adequately correct uremic acidosis.

Adult↗

Bicarbonate is an essential constituent of the water-oxidizing complex of photosystem II.

It is shown that restoration of photoinduced electron flow and O2 evolution with Mn2+ in Mn-depleted photosystem II (PSII) membrane fragments isolated from spinach chloroplasts is considerably increased with bicarbonate in the region pH 5.0-8.0 in bicarbonate-depleted medium. In buffered solutions equilibrated with the atmosphere (nondepleted of bicarbonate), the bicarbonate effect is observed only at pH lower than the pK of H2CO3 dissociation (6.4), which indicates that HCO3- is the essential species for the restoration effect. The addition of just 2 Mn2+ atoms per one PSII reaction center is enough for the maximal reactivation when bicarbonate is present in the medium. Analysis of bicarbonate concentration dependence of the restoration effect reveals two binding sites for bicarbonate with apparent dissociation constant (Kd) of approximately 2.5 microM and 20-34 microM when 2,6-dichloro-p-benzoquinone is used as electron acceptor, while in the presence of silicomolybdate only the latter one remains. Similar bicarbonate concentration dependence of O2 evolution was obtained in untreated Mn-containing PSII membrane fragments. It is suggested that the Kd of 20-34 microM is associated with the donor side of PSII while the location of the lower Kd binding site is not quite clear. The conclusion is made that bicarbonate is an essential constituent of the water-oxidizing complex of PSII, important for its assembly and maintenance in the functionally active state.

Journal Article↗

C Fixation by Leaves and Leaf Cell Protoplasts of the Submerged Aquatic Angiosperm Potamogeton lucens: Carbon Dioxide or Bicarbonate?

Protoplasts were isolated from leaves of the aquatic angiosperm Potamogeton lucens L. The leaves utilize bicarbonate as a carbon source for photosynthesis, and show polarity; that is, acidification of the periplasmic space of the lower, and alkalinization of the space near the upper leaf side. At present there are two models under consideration for this photosynthetic bicarbonate utilization process: conversion of bicarbonate into free carbon dioxide as a result of acidification and, second, a bicarbonate-proton symport across the plasma membrane. Carbon fixation of protoplasts was studied at different pH values and compared with that in leaf strips. Using the isotopic disequilibrium technique, it was established that carbon dioxide and not bicarbonate was the form in which DIC actually crossed the plasma membrane. It is concluded that there is probably no true bicarbonate transport system at the plasma membrane of these cells and that bicarbonate utilization in this species apparently rests on the conversion of bicarbonate into carbon dioxide. Experiments with acetazolamide, an inhibitor of periplasmic carbonic anhydrase, and direct measurements of carbonic anhydrase activity in intact leaves indicate that in this species the role of this enzyme for periplasmic conversion of bicarbonate into carbon dioxide is insignificant.

Journal Article↗

Hypertonic sodium bicarbonate partially reverses QRS prolongation due to flecainide in rats.

Hypertonic (1M) sodium bicarbonate can partially reverse the cardiac toxicity of some Class IA antiarrhythmic agents, presumably by antagonizing sodium channel inhibition. We studied the effects of 1M sodium bicarbonate on toxicity due to the Class IC drug flecainide. Anesthetized rats received i.v. loading and maintenance doses of flecainide to produce QRS prolongation of 76% that was stable over the 60 min study period. 20 min after the start of the maintenance infusion, groups of 8 rats received an i.v. infusion of 1M sodium bicarbonate (6 meq/kg) or an equal volume of 0.9% saline. QRS prolongation was reduced by 1M sodium bicarbonate but not only 0.9% saline (% change -12.2 +/- 10.0 v. +3.0 +/- 2.7, p = 0.001). Expressed as a percent of the flecainide-induced QRS prolongation, bicarbonate reduced this prolongation by 26.5%. The improvement in QRS duration persisted until sacrifice 30 min later. Compared to controls, the bicarbonate group had a significantly higher blood pH (7.55 +/- 0.06 v. 7.44 +/- 0.05) and serum sodium concentration (149 +/- 5 v. 137 +/- 2 meq/l). Serum flecainide concentrations were similar. These data suggest that 1M sodium bicarbonate can partially reverse flecainide-induced conduction delay in rats. This effect may be due to changes in the extracellular pH and sodium concentration. 1M sodium bicarbonate may be useful in assessing the role of sodium channel inhibition in mediating the toxicity of flecainide or other Class IC drugs.

Animals↗

Potassium bicarbonate supplementation blocks the hypocalciuric response to hydrochlorothiazide in rats.

Bicarbonate salts and thiazide diuretics each lower urinary calcium excretion. This study was undertaken to compare the effects of administering oral sodium or potassium bicarbonate supplements (4.5 mmol./day of each salt) each with or without hydrochlorothiazide (10 mg./kg. body weight/day) on urinary calcium excretion in rats. Urinary calcium decreased (p less than 0.01) by about 50 per cent after sodium bicarbonate supplementation and potassium bicarbonate supplementation. The hypocalciuric response to each bicarbonate salt was similar. However, although hydrochlorothiazide depressed urinary calcium in rats consuming sodium bicarbonate, rats receiving equimolar supplements of potassium bicarbonate did not lower urinary calcium when given hydrochlorothiazide, despite evidence of the expected thiazide-mediated diuresis. It is concluded that in the rat potassium bicarbonate loading blocks the ability of hydrochlorothiazide to lower urinary calcium excretion.

Animals↗

The effects of sodium bicarbonate and pyridoxine-alpha-ketoglutarate on short-term maximal exercise capacity.

The purpose of this study was to determine the effects of the simultaneous use of pyridoxine-alpha-ketoglutarate (PAK) and sodium bicarbonate (NaHCO3) on short-term maximal exercise capacity in eight well-trained male cyclists. The study consisted of the determination of maximal power output and the administration of various combinations of placebos, PAK and NaHCO3, followed by a short-term maximal exercise test. To determine maximal power output (power(max)), the subjects performed a continuous, incremental test on a Monark bicycle ergometer to symptom limited maximum (test 1). To determine the effects of NaHCO3 and PAK on short-term maximal exercise performance, the subjects were administered either placebo (PLA), PAK and sodium bicarbonate (P/B), PAK and placebo (PAK), or sodium bicarbonate and placebo (BIC) prior to performing short-term maximal exercise (test 2). Oral tablets of NaHCO3 and PAK were given in doses of 200 mg kg-1 and 50 mg kg-1 respectively. The subjects pedalled at the power output corresponding to 100% of their VO2 max at 70 rev min-1 until voluntary cessation or until they were unable to maintain pedal revolution rate. Venous blood samples were drawn at rest (RES), cessation of exercise (CES) and after 2 min of recovery (REC) and analysed for lactate, pH and bicarbonate ion concentration. The subjects attained an average maximum power output of 377 +/- 20 W during the graded maximal pre-test (test 1). There were no significant differences between treatments in the ability to sustain power(max) during test 2. During test 2, the subjects were able to sustain power(max) for 7.6 +/- 4.3 min with P/B, 6.7 +/- 2.9 min with PAK, 7.3 +/- 4.9 min with BIC and 6.9 +/- 2.7 min with placebo (mean +/- S.E.). Blood lactate (BLa) was significantly elevated at cessation of exercise and remained elevated during recovery, but there were no significant differences between treatments. Bicarbonate fell significantly during exercise and recovery in each treatment. At rest, bicarbonate levels were significantly higher in both the P/B and BIC than in the PAK or PLA treatments. Pooled data from the P/B and BIC treatments demonstrated a significant increase in pH at rest and end of exercise when compared to PLA treatment. These data suggest that sodium bicarbonate rather than PAK was responsible for this increase. In summary, our data suggest that in the dosages used in this study, administration of sodium bicarbonate or PAK, alone or in combination, is ineffective in increasing short-term maximal exercise capacity.

Adult↗

Effects of sodium bicarbonate on cardiorespiratory measurements and exercise capacity in thoroughbred horses.

We examined the effects of sodium bicarbonate in 6 Thoroughbred horses during submaximal and maximal treadmill exercise. Cardiorespiratory function was assessed together with the effect on exercise capacity by determining the run time to fatigue at maximal intensities. To discriminate between sodium bicarbonate's alkalinising effects and the fluid shifts that could result from the high osmotic load, we administered an equimolar solution of sodium chloride as a control. The horses were given sodium bicarbonate (1 g/kg bwt) or an equivalent number of moles of sodium chloride by nasogastric tube. Arterial blood samples were collected before exercise and 5 h after treatment, resulting in mean standard bicarbonate values of 39.6 mmol/l in horses treated with sodium bicarbonate compared with 24.2 mmol/l in horses that received saline. The horses were exercised on a treadmill at 40, 60 and 80% of their VO2max for 4, 2 and 2 mins respectively. The horses were walked for 3 mins and accelerated rapidly to a speed approximately equivalent to 110% VO2max and run until fatigued. The horses ran for 170 +/- 20 secs (mean +/- sem) after administration of sodium bicarbonate compared with 128 +/- 13 secs after receiving sodium chloride (P < 0.02). At rest and throughout submaximal and maximal exercise, the bicarbonate-treated horses had significantly lower arterial oxygen tensions and higher arterial carbon dioxide tensions. There were no differences in cardiac output, heart rate, oxygen uptake or carbon dioxide production between the saline and bicarbonate treatments.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Influence of sodium bicarbonate on growth and health of young calves.

Fifty-four Holstein and Jersey calves were assigned at 4 days of age within breed and sex to one of four treatments: control consisting of colostrum, milk replacer, and starter; buffered colostrum and replacer (.6% sodium bicarbonate) and starter (2% sodium bicarbonate); acidified colostrum (1% propionic), untreated replacer, and starter; and acidified, buffered colostrum (1% propionic, .6% sodium bicarbonate), buffered replacer (.6% sodium bicarbonate), and starter (2% sodium bicarbonate). The feeding regimen was colostrum once daily, day 4 to 14; milk replacer once daily, day 15 to 28; and calf starter ad libitum, day 4 to 84. Bull calves were fed for 42 days and heifers for 84 days. Calves fed acidified colostrum refused more feed and were less efficient from day 4 to 14 than calves fed buffered colostrum. Bulls were more sensitive to acidified colostrum than heifers. Starter intake, total dry matter intake, and average daily gains were similar for all calves during days 4 to 84. Rumen fluid from calves fed diets with sodium bicarbonate was higher in acetate and lower in propionate and lactate than that from calves fed diets without sodium bicarbonate. Sodium bicarbonate improved intake of acidified colostrum during the first 2 or 3 days of feeding but had no other effect on gain or feed intake.

Animals↗

The effect of carbonic anhydrase inhibition on bicarbonate reabsorption.

Renal reabsorption of bicarbonate was studied in Merino ewes during carbonic anhydrase inhibition. Bicarbonate reabsorption was directly proportional to plasma bicarbonate concentration. No tubular maximum for bicarbonate was demonstrated. Elevation of arterial PCO2 or depression of arterial pH caused slight increases in bicarbonate reabsorption. The data suggest that bicarbonate is reabsorbed by 2 distinct processes. The quantitatively more significant process may involve ionic reabsorption of bicarbonate secondary to Na+ reabsorption and a relatively minor part of bicarbonate reabsorption may be secondary to H+ secretion.

Acetazolamide↗

Effect of enprostil on amphibian gastroduodenal and human gastric bicarbonate secretion.

The protective and ulcer healing properties of prostaglandins are well established. We have explored the possible mode of action of enprostil, a synthetic dehydroprostaglandin E2, on amphibian gastroduodenal mucosal bicarbonate secretion in vitro and on human gastric bicarbonate secretion in vivo. Addition of enprostil (10(-6) M) to the luminal solution of isolated amphibian gastric mucosa produced a 28% increase in bicarbonate secretion without a change in transmucosal potential difference. The same concentration of enprostil added to the luminal solution of isolated amphibian duodenal mucosa produced a 37% increase in bicarbonate secretion and was associated with a rise in transmucosal potential difference. The gastric output of bicarbonate from the human stomach has been calculated using a perfusion technique before, during, and after perfusion with enprostil (35 micrograms) in six healthy volunteers. A significant 78% increase in bicarbonate secretion occurred during the period of enprostil perfusion, falling to normal during the postenprostil period. These changes were caused mainly by an increase in gastric secretory volume with insignificant increases in bicarbonate concentration. These results suggest that stimulation of gastroduodenal bicarbonate secretion by enprostil may play a role in its protective actions.

Adult↗

Hydrogen peroxide production is an early event during bicarbonate induced stomatal closure in abaxial epidermis of Arabidopsis.

The presence of 2 mM bicarbonate in the incubation medium induced stomatal closure in abaxial epidermis of Arabidopsis. Exposure to 2 mM bicarbonate elevated the levels of H(2)O(2) in guard cells within 5 min, as indicated by the fluorescent probe, dichlorofluorescein diacetate (H(2)DCF-DA). Bicarbonate-induced stomatal closure as well as H(2)O(2) production were restricted by exogenous catalase or diphenylene iodonium (DPI, an inhibitor of NAD(P)H oxidase). The reduced sensitivity of stomata to bicarbonate and H(2)O(2) production in homozygous atrbohD/F double mutant of Arabidopsis confirmed that NADP(H) oxidase is involved during bicarbonate induced ROS production in guard cells. The production of H(2)O(2) was quicker and greater with ABA than that with bicarbonate. Such pattern of H(2)O(2) production may be one of the reasons for ABA being more effective than bicarbonate, in promoting stomatal closure. Our results demonstrate that H(2)O(2) is an essential secondary messenger during bicarbonate induced stomatal closure in Arabidopsis.

Abscisic Acid↗

Determination of urinary bicarbonate with the Henderson-Hasselbalch equation. Comparison using two different methods.

The determination of urinary bicarbonate with the Henderson-Hasselbalch equation was compared using two methods: (1) correcting the pK in every urine sample according to ionic strength and using the solubility constant of CO2 in urine (alpha=0.0309) and (2) using a fixed pK value (6.1) and a CO2 solubility constant of 0.0301, which we use to calculate blood bicarbonate. Nine patients were studied and 29 determinations were performed. A high correlation was found between the methods (r=0.99). Bicarbonate calculated with corrected pK was 24.3+/-6.6 mEq/l (95% confidence interval 11.4-37.2) and bicarbonate calculated with pK fixed at 6.1 was 25.6+/-6.6 mEq/l (95% confidence interval 12.7-38.5). For each urine sample, the delta bicarbonate was calculated as the difference between the bicarbonate obtained with pK at 6.1 minus that obtained with the corrected pK (mean 1.25, standard error 0.83, P=0.15). This indicates that the difference between the methods was not significant. No difference was found whether pK was corrected or fixed (6.1). Therefore, our results suggest that it is valid to take the value shown by the equipment for blood gas determination as the urinary bicarbonate value. This would allow the rapid and accurate determination of urinary bicarbonate in patients with hyperchloremic acidosis, especially those with renal tubular acidosis.

Acidosis, Renal Tubular↗

Bicarbonate exchange between body compartments after changes of temperature in the larger spotted dogfish (Soyliorhinus stellaris).

Intracellular/extracellular and extracellular/sea-water bicarbonate exchanges were measured in Larger Spotted Dogfish (Sycliorhinus stellaris) exposed to 10 degrees C temperature step changes in a closed sea-water recirculation system. Changes of the bicarbonate concentration in blood plasma (= extracellular space) and in the recirculating sea-water were monitored for 36 h after the temperature change. Intracellular/extracellular transfer of bicarbonate was computed from bicarbonate changes in the extracellular space and sea-water. When the temperature was changed from 10 to 20 degrees C a signigicant transfer of bicarbonate was observed from the intracellular to the extracellular compartment and from the extracellular compartment to the sea-water. These transfers were reversed when the temperature was lowered from 20 to 10 degrees C. The exchange processes were practically completed after 18 h. The amount of bicarbonate exchanged between intracellular and extracellular compartments and sea-water was larger than predicted on the basis of in vitro buffer values of white, red and heart muscle, suggesting that additional tissues exchange significant amounts of bicarbonate with the extracellular space. It is concluded that physicochemical buffering is not sufficient to account for the observed adjustment of intracellular and extracellular pH and that bicarbonate exchange between body compartments and environment may be the most important regulatory mechamism, responsible for the final adjustment of acid-base balance in dogfish.

Acid-Base Equilibrium↗

Increase in bicarbonate stores with exercise.

We previously described bicarbonate exchange dynamics in humans at rest and during exercise using a three-compartment model. In the present study we tested the effect of certain assumptions of this model on the prediction of the change in exchangeable bicarbonate with the increased metabolic rate of exercise. We compared this prediction with a measurement of CO2 retention after exercise onset determined from gas exchange data. The change in tissue bicarbonate stores was estimated from differences in the kinetics of adjustment of VO2 and VCO2, and this was added to an estimate of the changes in venous blood gas stores to estimate the total change in bicarbonate. When the commonly held assumption that endogenous CO2 production, thought to occur in a rapidly equilibrating peripheral compartment at rest, was also applied to the exercise condition, the three-compartment bicarbonate model predicted an unphysiologically large increase in bicarbonate stores (700 mmol, or over 15 L). In contrast, the 'gas exchange' approach predicted a relatively small increase in bicarbonate (26 mmol), consistent with other reports. The incompatibility of these findings with the assumption about the source of endogenous CO2 production in the bicarbonate model requires that the underlying physiological correlates of the three compartments change from rest to exercise.

Bicarbonates↗

Effects of neuropeptides on gastric acid and duodenal bicarbonate secretions in freely moving rats.

The central nervous system effects of neuropeptides on gastric acid and duodenal bicarbonate secretions were examined. In freely moving rats, i.c.v. administration of thyrotropin-releasing hormone (TRH), human gastrin-17 (hG-17) and the somatostatin analogue, desAA 1,2,4,5,12,13 [D-Trp8]somatostatin (ODT8-SS), significantly increased gastric acid secretion, while vasoactive intestinal peptide (VIP) had no effect. In the order of potency and efficacy, the following peptides decreased acid secretion: bombesin (BOM) greater than calcitonin gene-related peptide (CGRP) greater than calcitonin (CT) greater than corticotropin-releasing factor (CRF) greater than beta-endorphin (beta-END) greater than neurotensin (NT). In anesthetized rats, none of these peptides significantly altered proximal duodenal bicarbonate secretion. In awake, freely moving rats, cerebroventricular administration of CGRP significantly decreased while ODT8-SS, TRH and CRF significantly increased duodenal bicarbonate secretion. beta-Endorphin, VIP, CT, BOM, NT and hG-17 given i.c.v. did not significantly alter the bicarbonate response. These results indicate that neuropeptides administered into the central nervous system modulate gastric acid as well as duodenal bicarbonate secretions in awake, freely moving rats in a differentiated fashion. CGRP inhibits both acid and bicarbonate secretions, a somatostatin analogue and TRH both stimulate acid and bicarbonate secretions and CRF inhibits gastric acid but stimulates duodenal bicarbonate secretions.

Animals↗

Bicarbonate requirement for the water-oxidizing complex of photosystem II.

It is well established that bicarbonate stimulates electron transfer between the primary and secondary electron acceptors, Q(A) and Q(B), in formate-inhibited photosystem II; the non-heme Fe between Q(A) and Q(B) plays an essential role in the bicarbonate binding. Strong evidence of a bicarbonate requirement for the water-oxidizing complex (WOC), both O2 evolving and assembling from apo-WOC and Mn2+, of photosystem II (PSII) preparations has been presented in a number of publications during the last 5 years. The following explanations for the involvement of bicarbonate in the events on the donor side of PSII are considered: (1) bicarbonate serves as an electron donor (alternative to water or as a way of involvement of water molecules in the oxidative reactions) to the Mn-containing O2 center; (2) bicarbonate facilitates reassembly of the WOC from apo-WOC and Mn2+ due to formation of the complexes MnHCO3+ and Mn(HCO3)2 leading to an easier oxidation of Mn2+ with PSII; (3) bicarbonate is an integral component of the WOC essential for its function and stability; it may be considered a direct ligand to the Mn cluster; (4) the WOC is stabilized by bicarbonate through its binding to other components of PSII.

Bicarbonates↗

Effect of graded doses of intraluminal H+, prostaglandin E2, and inhibition of endogenous prostaglandin synthesis on proximal duodenal bicarbonate secretion in unanesthetized rat.

The purpose of this study was to examine the effect of graded doses of intraluminal HCl and prostaglandin E2 on proximal duodenal bicarbonate secretion in unanesthetized rats. Basal bicarbonate secretion was approximately 14 mumol/cm . h and increased significantly in a dose-related manner to 50, 100, and 150 mM HCl as follows: 22.0 +/- 1.5, 29.2 +/- 4.0, and 42.0 +/- 4.3 mumol/cm . h, respectively (mean +/- SE). After a single 5-min infusion of 150 mM HCl, duodenal bicarbonate secretion remained significantly above basal for almost 3 h. The responses to 100 mM HCl and 10(-4) M prostaglandin E2 were similar (29.2 +/- 4.0 and 26.9 +/- 4.4 mumol/cm . h, respectively). Indomethacin (4 mg/kg, intraperitoneally) suppressed the bicarbonate response to 150 mM HCl; whereas the response to 10(-4) M prostaglandin E2 was unaltered. These studies in the in vivo rat indicate that (a) graded doses of intraluminal HCl produced graded increases in proximal duodenal bicarbonate secretion; (b) the bicarbonate output in response to a 5-min infusion of HCl persisted for almost 3 h; and (c) the bicarbonate response to HCl was essentially abolished by indomethacin pretreatment, suggesting that endogenous prostaglandins are at least in part involved in acid-induced proximal duodenal bicarbonate secretion.

Animals↗

The role of bicarbonate and fluid loading in improving resuscitation from prolonged cardiac arrest with rapid manual chest compression CPR.

Rapid manual chest compression (120 compressions/min) CPR has been shown to improve hemodynamics and survival when compared with standard CPR (60 compressions/min) in a canine model of prolonged cardiac arrest. The study showing improved survival with rapid manual CPR empirically included treatment with bicarbonate and initial fluid loading. To determine the role of bicarbonate and fluid loading in the success of rapid manual chest compression CPR, 31 mongrel dogs were studied. After instrumentation with micromanometer-tipped catheters to measure aortic and right atrial pressures, the animals were assigned sequentially to three treatment groups. Group A underwent rapid manual chest compressions at 120 compressions/min, bicarbonate treatment, and initial fluid loading. Group B underwent rapid manual compressions at 120 compressions/min without bicarbonate or fluid loading. Group C underwent standard CPR at 80 compressions/min with bicarbonate and fluid loading. After 30 minutes of ventricular fibrillation, defibrillation was attempted. Seven of 11 dogs in group A survived 24 hours. None of the animals in group B resuscitated or survived. Three of the ten dogs in group C survived 24 hours. Survival with rapid manual CPR without bicarbonate and initial fluid loading was significantly less than when these interventions were used (P less than .01). To examine the separate contribution of bicarbonate and fluid therapy, two additional groups of animals were studied. Fourteen animals (group D) received rapid manual CPR with bicarbonate therapy, and 12 (group E) received rapid manual CPR with fluid loading only.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗