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A small dose of somatostatin inhibits the secretin stimulated secretion of bicarbonate, amylase, and chymotrypsin in man.

The effects of a small dose of somatostatin (0.025 mg/h) on the pancreatic secretion of bicarbonate, amylase, and chymotrypsin during stepwise increasing doses of secretin was examined in six healthy volunteers. The secretion of bicarbonate, amylase, and chymotrypsin in response to secretin was significantly reduced by somatostatin. Both output and concentration of pancreatic enzymes were reduced, whereas the concentration of bicarbonate remained unchanged. The pattern of inhibition suggests that somatostatin is a competitive inhibitor of secretin in the stimulation of pancreatic secretion of bicarbonate, which supports the hypothesis of a direct effect of somatostatin on the exocrine secretory cells of the pancreas. The pattern of inhibition of amylase and chymotrypsin secretion is different and difficult to interpret from the present study, but somatostatin may inhibit also the secretin stimulated pancreatic secretion of enzymes completely, as the inhibitory effect seemed to decline when larger doses of secretin were applied.

Amylases↗

Effect of bicarbonate and lactate buffer on glucose and lactate metabolism during hemodiafiltration in patients with multiple organ failure.

OBJECTIVE: To compare the effects of sodium bicarbonate and lactate for continuous veno-venous hemodiafiltration (CVVHDF) in critically ill patients. DESIGN AND SETTINGS: Prospective crossed-over controlled trial in the surgical and medical ICUs of a university hospital. PATIENTS: Eight patients with multiple organ dysfunction syndrome (MODS) requiring CVVHDF. INTERVENTION: Each patient received the two buffers in a randomized sequence over two consecutive days. MEASUREMENTS AND RESULTS: The following variables were determined: acid-base parameters, lactate production and utilization ((13)C lactate infusion), glucose turnover (6,6(2)H(2)-glucose), gas exchange (indirect calorimetry). No side effect was observed during lactate administration. Baseline arterial acid-base variables were equal with the two buffers. Arterial lactate (2.9 versus 1.5 mmol/l), glycemia (+18%) and glucose turnover (+23%) were higher in the lactate period. Bicarbonate and glucose losses in CVVHDF were substantial, but not lactate elimination. Infusing (13)C lactate increased plasma lactate levels equally with the two buffers. Lactate clearance (7.8+/-0.8 vs 7.5+/-0.8 ml/kg per min in the bicarbonate and lactate periods) and endogenous production rates (14.0+/-2.6 vs 13.6+/-2.6 mmol/kg per min) were similar. (13)C lactate was used as a metabolic substrate, as shown by (13)CO(2) excretion. Glycemia and metabolic rate increased significantly and similarly during the two periods during lactate infusion. CONCLUSION: Lactate was rapidly cleared from the blood of critically ill patients without acute liver failure requiring CVVHDF, being transformed into glucose or oxidized. Lactate did not exert undesirable effects, except moderate hyperglycemia, and achieved comparable effects on acid-base balance to bicarbonate.

Acid-Base Equilibrium↗

Impact of a bicarbonated saline solution on early resuscitation after major burns.

OBJECTIVE: The study aimed at assessing the impact of the introduction of a bicarbonated saline solution on total fluid load, weight gain and acid base status during acute burn resuscitation. DESIGN: Based on a retrospective patient record review. SETTING: Burn care centre of a surgical ICU in a tertiary university hospital. PATIENTS: Two groups of adult patients (20/20), with thermal burns of 25% or more body surface area were studied. INTERVENTION: Modification of the resuscitation fluid composition from lactated Ringer's solution (LR: Na 132 mmol/l, Cl 112 mmol/l, 263 mosm/l), to bicarbonated 0.9% saline (BS: Na 180 mmol/l, Cl 154 mmol/l, 340 mosm/l) METHODS: Age, weight, burn size and depth, inhalation injury, fluid intakes over 48 h post-injury, plasma sodium, chloride, creatinine, albumin levels, blood gases and ventilation support were recorded. RESULTS: The demographic characteristics of the patients (41 +/- 16 years) in the two groups were not different, with severe burns involving 44 +/- 17% body surface area. While the total fluid volumes administered did not differ, BS was associated with lower plasma pH, base excess and bicarbonate levels for 24 h and with hyperchloraemia. Clinical evolution did not differ. CONCLUSIONS: Using bicarbonated saline solution for resuscitation causes a transient hyperchloraemic dilutional acidosis compared with LR, and has no other detectable clinical impact over the first 10 days after severe burn injury.

Adult↗

Effects of potassium bicarbonate supplementation on axial and peripheral bone mass in rats on strenuous treadmill training exercise.

We administered a potassium bicarbonate supplement to rats on strenuous treadmill training in order to determine the effect on bone mass and the metabolic acidosis seen with this type of training. A sample of 45 93-day-old female Wistar rats with a mean initial weight of 267 +/- 17 g were studied. The control group (15 rats) was not exercised or given potassium bicarbonate (Ex- PB-). The experimental group (30 rats) was randomly divided into two subgroups of 15 rats each, one that exercised and did not receive potassium bicarbonate (Ex+ PB-) and one that exercised and received potassium bicarbonate (Ex+ PB+), at a dose of 0.05 mg/kg/day administered by esophageal catheter on exercise days. Training consisted of treadmill running on 5 out of 7 days for a period of 11 weeks. Running time, treadmill speed, and the percent grade were gradually increased until week 7, then maintained until rats were sacrificed at the ened of 11 weeks. The bone mineral content (BMC) and bone mineral density (BMD) of the whole right femur and 5th lumbar vertebra were measured. Femoral and vertebral length were also measured. Femur length, weight, BMC, and BMD, and femur BMC/final weight ratio, and vertebral weight, BMD, and BMC, and vertebral BMC/final weight ratio were lower in the Ex+ PB- group than in either the controls or the Ex+ PB+ group (P < 0.01-P < 0.0001); the length of the 5th lumbar vertebra did not differ between groups.

Animals↗

A comparison of the effects of potassium citrate and sodium bicarbonate in the alkalinization of urine in homozygous cystinuria.

For many years, urine alkalinization has been one of the cornerstones in the treatment of homozygous cystinuria. Because of the relationship found between the excretion of urinary sodium and cystine, potassium citrate has emerged as the preferred sodium-free alkalizing agent. To evaluate the usefulness of potassium citrate for urine alkalization in cystinuric patients, sodium bicarbonate and potassium citrate were compared in 14 patients (10 on tiopronin treatment and four without treatment with sulfhydryl compounds). The study started with 1 week without the use of any alkalizing agents (Period 0) followed by 2 weeks with sodium bicarbonate (Period 1) and 2 weeks with potassium citrate (Period 2). Urinary pH, volume, excretion of sodium, potassium, citrate and free cystine, as well as the plasma potassium concentration, were recorded. Potassium citrate was shown to be effective as an alkalizing agent and, in this respect, not significantly different from sodium bicarbonate. Even though a normal diet was used, a significant increase in urinary sodium excretion was observed with sodium bicarbonate (Period 1). Urinary potassium and citrate excretion increased with potassium citrate (Period 2). A significant correlation was found between urinary sodium and cystine in the tio-pronin-treated patients. No significant differences in cystine excretion were recorded in Periods 0, 1 and 2. Plasma potassium was significantly higher during Period 2, but only one patient developed a mild hyperkalemia (5.0 mmol/l). The use of potassium citrate for urine alkalization in homozygous cystinuria is effective and can be recommended in the absence of severe renal impairment.

Adult↗

Sodium bicarbonate can be used as an ergogenic aid in high-intensity, competitive cycle ergometry of 1 h duration.

The aim of this study was to determine whether a dose of 300-mg x kg(-1) body mass of sodium bicarbonate would effect a high-intensity, 1-h maximal cycle ergometer effort. Ten male, well-trained [maximum oxygen consumption 67.3 (3.3) ml x kg(-1) x min(-1), mean (SD)] volunteer cyclists acted as subjects. Each undertook either a control (C), placebo (P), or experimental (E) ride in a random, double-blind fashion on a modified, air-braked cycle ergometer, attached to a personal computer to which the work and power data was downloaded at 10 Hz. Fingertip blood was sampled at 10-min intervals throughout the exercise. Blood was also sampled at 1, 3, 5, and 10 min post-exercise. Blood was analysed for lactate, partial pressure of Carbon dioxide and oxygen, pH and plasma bicarbonate (HCO-) concentration. Randomly chosen pairs of subjects were asked to complete as much work as possible during the 60-min exercise periods in an openly competitive situation. The sodium bicarbonate had the desired effect of increasing blood HCO3- prior to the start of the test. The subjects in E completed 950.9 (81.1) kJ of work, which was significantly more (F(2,27) = 5.28, P < 0.01) than during either the C [835.5 (100.2) kJ] or P [839.0 (88.6) kJ] trials. No differences were seen in peak power or in the power:mass ratio between these three groups. The results of this study suggest that sodium bicarbonate may be used to offset the fatigue process during high-intensity, aerobic cycling lasting 60 min.

Adult↗

Effects of chronic bicarbonate ingestion on the performance of high-intensity work.

We have evaluated whether sodium bicarbonate, taken chronically (0.5 g x kg(-1) body mass) for a period of 5 days would improve the performance of eight subjects during 60 s of high-intensity exercise on an electrically braked cycle ergometer. The first test was performed prior to chronic supplementation (pre-ingestion) while the post-ingestion test took place 6 days later. A control test took place approximately 1 month after the cessation of all testing. Acid-base and metabolite data (n = 7) were measured from arterialised blood both pre- and post-exercise, as well as daily throughout the exercise period. The work completed by the subjects in the control and pre-ingestion test [21.1 (0.9) and 21.1 (0.9) MJ, respectively] was less than (P<0.05) that completed in the post-ingestion test [24.1 (0.9) MJ; F(2,21) = 3.4, P<0.05, power = 0.57]. Peak power was higher after the 5-day supplementation period (P<0.05). Ingestion of the sodium bicarbonate for a period of 5 days resulted in an increase in pH (F(5,36) = 12.5, P<0.0001, power = 1.0) over the 5-day period. The blood bicarbonate levels also rose during the trial (P<0.05) from a resting level of 22.8 (0.4) to 28.4 (1.1) mmol x l(-1) after 24 h of ingestion. In conclusion, the addition of sodium bicarbonate to a normal diet proved to be of ergogenic benefit in the performance of short-term, high-intensity work.

Acid-Base Equilibrium↗

Carbon dioxide pneumoperitoneum causes severe peritoneal acidosis, unaltered by heating, humidification, or bicarbonate in a porcine model.

BACKGROUND: Carbon dioxide (CO(2)) is the most common gas used for insufflation in laparoscopy, but its effects on peritoneal physiology are poorly understood. This study looks at the changes in peritoneal and bowel serosal pH during CO(2) pneumoperitoneum, and whether heating and humidification with or without bicarbonate alters the outcomes. METHODS: Twenty-one pigs divided into four groups as follows: (1) standard (STD) laparoscopy (n = 5); (2) heated and humidified (HH) laparoscopy (n = 6); (3) heated and humidified with bicarbonate (HHBI) laparoscopy (n = 5); and (4) laparotomy (n = 5). Peritoneal pH, bowel serosal pH, and arterial blood gas (ABG) were obtained at 15-min intervals for 3 h. RESULTS: Severe peritoneal acidosis (pH range 6.59-6.74) was observed in all laparoscopy groups, and this was unaltered by heating and humidification or the addition of bicarbonate. Bowel serosal acidosis was observed in all laparoscopy groups with onset of pneumoperitoneum, but it recovered after 45 minutes. No significant changes in peritoneal or bowel serosal pH were observed in the laparotomy group. CONCLUSION: CO(2) pneumoperitoneum resulted in severe peritoneal acidosis that was unaltered by heating and humidification with or without bicarbonate. Alteration in peritoneal pH may conceivably be responsible for providing an environment favorable for tumor-cell implantation during laparoscopy.

Acidosis↗

Duodenal secretion of phospholipase A2, amylase, and bicarbonate in chronic pancreatitis.

Phospholipase A2 has been suggested to be involved in the pathogenesis and pathophysiology of acute pancreatitis. We determined phospholipase A2 and amylase activities in duodenal juice collected during a secretin test from 30 consecutive patients who were suspected to have chronic pancreatitis or biliary disease. The patients underwent endoscopic retrograde cholangiopancreatography (ERCP) the following day. In the 8 patients with ERCP findings of advanced chronic pancreatitis, the mean outputs of phospholipase A2, amylase, and bicarbonate were reduced by 74%, 72%, and 60% compared to the respective values in the 13 (control) patients without a diagnosis of any pancreatic disorder or jaundice. In the 3 patients with recurrent pancreatitis but normal ERCP findings and in the 6 patients with jaundice the output values were not significantly reduced compared to those in the patients without any pancreatic disorder or jaundice. The outputs of amylase and phospholipase A2 were not significantly interrelated, whereas the outputs of phospholipase A2 and bicarbonate correlated well. Receiver characteristic (ROC) curves confirmed the high specificity and sensitivity of phospholipase A2 or bicarbonate output in patients with ERCP findings of advanced chronic pancreatitis compared to those with no changes in pancreatic ducts, with similar probability values of 0.880 +/- 0.111 (SEM), compared to the respective lower value of amylase, 0.676 +/- 0.118. Phospholipase A2 and bicarbonate output proved of equal value as markers of chronic pancreatitis and were superior to amylase output in the secretin test.

Acute Disease↗

Bicarbonate-buffered peritoneal dialysis. An effective adjunct in the treatment of lactic acidosis.

Severe lactic acidosis is associated with poor prognosis. Usually, the patient is treated with massive amounts of intravenous sodium bicarbonate, which in itself carries many undesirable consequences such as fluid overload and hypernatremia. We have successfully used peritoneal dialysis with a bicarbonate-buffered dialysate in the management of severe acidosis. Bicarbonate-buffered peritoneal dialysis provided an unlimited supply of physiologic buffer over a prolonged period without causing hypervolemia or hypernatremia. Furthermore, significant amounts of lactate were removed by dialysis. We, therefore, recommend the use of bicarbonate-buffered peritoneal dialysis as an adjunct in the treatment of severe lactic acidosis.

Acidosis↗

Protection of gastric mucosa against acute ulceration by intravenous infusion of sodium bicarbonate.

The influence of intravenous infusion of sodium bicarbonate on gastric mucosal injury induced by topical sodium taurocholate and hemorrhagic shock was assessed in a canine ex vivo model. As expected, exposure of the gastric mucosa to sodium taurocholate and acid resulted in excessive back diffusion of hydrogen ions (H+) and mild mucosal damage. This mucosal injury was enhanced by hemorrhagic shock in the control dogs. The degree of mucosal injury was significantly less in the test dogs that received intravenous infusions of sodium bicarbonate. The protection afforded by intravenous bicarbonate was not due to a reduction in the amount of H+ entering the tissue, since the net H+ loss from the lumen was not significantly different between the control and the test dogs. The protection effect of intravenous infusion of sodium bicarbonate is probably secondary to an enhancement of mucosal tolerance to H+. These results support the hypothesis that the enhancement of mucosal injury during hemorrhagic shock may be a result of a decrease in the ability of the gastric mucosa to buffer the influxing H+.

Animals↗

The effects of carbonic anhydrase inhibitors formate, bicarbonate, acetazolamide, and imidazole on photosystem II in maize chloroplasts.

Inhibitors of carbonic anhydrase were tested for their effects on Photosystem II (PS II) activity in chloroplasts. We find that formate inhibition of PS II turnover rates increases as the pH of the reaction medium is lowered. Bicarbonate ions can inhibit PS II turnover rates. The relative potency of the anionic inhibitors N-3, I-, OA-c, and Cl- is the same for both carbonic anhydrase and PS II. The inhibitory effect of acetazolamide on PS II increases as light intensity decreases, indicating a lowering of quantum yields in the presence of the inhibitor. Imidazole inhibition of PS II increases with pH in a manner suggesting that the unprotonated form of the compound is inhibitory. Formate, bicarbonate, acetazolamide, and imidazole all inhibit DCMU-insensitive, silicomolybdate-supported oxygen evolution, indicating that the site(s) of action of the inhibitors is at, or before, the primary stable PS II electron acceptor, Q. This inhibitory effect of low levels of HCO-3 along with the known enhancement by HCO-3 of quinone-mediated electron flow suggests an antagonistic control effect on PS II photochemistry. We conclude that the responses of PS II to anions (formate, bicarbonate), acetazolamide, and imidazole are analogous to the responses shown by carbonic anhydrase. These findings suggest that the enzyme carbonic anhydrase may provide a model system to gain insight into the "bicarbonate-effect" associated with PS II in chloroplasts.

Acetazolamide↗

A new site of bicarbonate effect in photosystem II of photosynthesis: evidence from chlorophyll fluorescence transients in spinach chloroplasts.

Recent studies on oxygen evolution of corn chloroplast fragments in flashing light [Stemler, A., Babcock, G.T. and Govindjee (1974) Proc. Natl. Acad. Sci. 71, 4679-4683] have shown that the absence of bicarbonate ions increases the turnover time of the Photosystem II reaction center. The rate limiting steps in Photosystem II turnover can be interpreted in terms of reactions either on the oxidizing (electron donor) or reducing (electron acceptor) side of the reaction center. Experiments are reported here that suggest at least one site of bicarbonate action on the reducing side. In Tris-washed spinach chloroplasts (incapable of O2 evolution), the chlorophyll a fluorescence transient in the presence of various artificial electron donors (hydroquinone, diphenylcarbazide, MnCl2 and NH2OH) and in the absence of bicarbonate ions shows a rapid initial rise; the addition of 10 mM NaHCO3 restores the transient to one characteristic of normal chloroplast. Furthermore, the transients measured as a function of decreasing bicarbonate concentrations are qualitatively similar to those observed with increasing concentrations of 3-(3, 4-dichlorophenyl)-1, 1-dimethyl urea which imposes a block on the reducing side, rather than to transients observed with increasing concentrations of NH2OH or prolonged heat treatments, which impose a block on the oxidizing side.

2,6-Dichloroindophenol↗

Inhibition of the reoxidation of the secondary electron acceptor of photosystem II by bicarbonate depletion.

In bicarbonate-depleted chloroplasts, the chlorophyll a fluorescence decayed with a halftime of about 150 ms after the third flash, and appreciably faster after the first and second flash of a series of flashes given after a dark period. After the fourth to twentieth flashes, the decay was also slow. After addition of bicarbonate, the decay was fast after all the flashes of the sequence. This indicates that the bicarbonate depletion inhibits the reoxidation of the secondary acceptor R2- by the plastoquinone pool; R is the secondary electron acceptor of pigment system II, as it accepts electrons from the reduced form of the primary electron acceptor (Q-). This conclusion is consistent with the measurements of the DCMU (3-(3,4-dichlorophenyl)-),)-dimethylurea)- induced chlorophyll a fluorescence after a series of flashes in the presence and the absence of bicarbonate, if it is assumed that DCMU not only causes reduction of Q if added in the state QR-, but also if added in the state QT2-.

Bicarbonates↗

Gadolinium block of calcium channels: influence of bicarbonate.

The selectivity of block of voltage-activated barium (Ba2+) currents by lanthanide ions was studied in a rat dorsal root ganglion (DRG) cell line (F11-B9), rat and frog peripheral neurons, and rat cardiac myocytes using the whole-cell patch clamp technique. Gadolinium (Gd3+) produced a dose-dependent and complete inhibition of whole-cell Ba2+ current in all cells studied, including cells expressing identified dihydropyridine-sensitive L-type currents and omega-conotoxin-sensitive N-type currents. Like Gd3+, lutetium (Lu3+) and lanthanum (La3+) blocked all Ba2+ current with little selectivity for different components of the whole-cell current. Gd3+ block of Ba2+ currents was incomplete, however, when sodium bicarbonate (5-22.6 mM) was added to the standard HEPES-buffered external Ba2+ solution. In rat DRG neurons and F11-B9 cells, a fraction of the whole-cell Ba2+ current recorded in the presence of bicarbonate was resistant to block by saturating concentrations of Gd3+ (50-100 microM). The resistant current inactivated more rapidly than the original current giving the appearance that, under these conditions, Gd3+ block is more selective for the slowly inactivating component of the whole-cell current. Bicarbonate modification of Gd3+ block occurred both before and after omega-conotoxin block of N-type currents in rat DRG neurons, suggesting that even in the presence of bicarbonate, Gd3+ block was not selective for N-type currents.

Animals↗

Assessment of the 'mucus-bicarbonate' barrier in the stomach of patients with chronic gastric disorders.

The composition of gastric mucus and the amount of gastric bicarbonate secretion have been investigated in 26 subjects including healthy controls, duodenal ulcer patients and subjects with chronic gastric disorders (benign gastric ulcer or chronic superficial gastritis). Qualitative changes in gastric mucus (expressed as a reduction in the values of 'mucoprotective index') were found in the gastric ulcer group, but not in patients with chronic superficial gastritis. Basal bicarbonate secretion was significantly reduced (p less than 0.01) in subjects with gastric ulcer and chronic gastritis, compared with healthy controls. Mucus secretion and bicarbonate production proved to be normal in duodenal ulcer patients. Our results support the concept that impairment of the 'mucus-bicarbonate' barrier is an important pathogenetic factor in gastric ulcer and chronic gastritis.

Adult↗

Rod photoreceptor disc shedding in eye cups: relationship to bicarbonate and amino acids.

We previously demonstrated that disc shedding in eye cups from Xenopus laevis depends on medium bicarbonate concentration, but also found that other unidentified medium components influenced the response. Here, in order to determine which medium components influence shedding, we used high bicarbonate salt solutions supplemented with medium components in amphibian tissue culture medium. Compared to the high bicarbonate salt solution alone, addition of fetal bovine serum or whole egg ultrafiltrate enhanced disc shedding. However, a response fully comparable to that in intact animals was obtained on addition of a mixture of 14 amino acids. The full light-evoked response depended on the simultaneous presence of high bicarbonate (35 mM) and amino acids. In the presence of amino acids, photoreceptor tips and RPE showed tight interdigitation and less tendency for in vitro separation, suggesting that these medium components promote such interdigitation. Using the defined medium we have additionally shown that shedding is related to HCO3- concentration under conditions of controlled medium pH, Cl- content and osmolality.

Amino Acids↗

Effects of ambient bicarbonate, phosphate and carbonic anhydrase inhibitors on fluid transport across rabbit corneal endothelium.

Bicarbonate has been long held to be indispensable for fluid pumping by the endothelium; however, such need has been disputed recently. We investigated this issue and found that: (1) the corneal endothelium pumps fluid equally well (at 6-8 microliters hr-1 cm-2) whether the bathing solution contains 43 mM bicarbonate or 10 mM phosphate, (2) if bicarbonate and most of the phosphate are absent, fluid pumping is noticeably lowered (2-4 microliters hr-1 cm-2), (3) carbonic anhydrase inhibitors (5 mM acetazolamide; 0.1, 0.2 and 0.3 mM ethoxzolamide) block this lowered fluid pumping, and (4) in the absence of external bicarbonate, 20 mM HEPES is insufficient to preserve adequate fluid pumping. These results are consistent with existing models for endothelial transport in which exogenous and endogenous CO2 are converted to HCO3- by carbonic anhydrase, with HCO3- fueling the transport mechanism and therefore the fluid pump.

Acetazolamide↗