The effects of sodium hydrogen carbonate ingestion during the recovery period between two 200-m front-crawl time trials.

PURPOSE: The aim of this study was to determine how sodium hydrogen carbonate (NaHCO3) ingestion during a 1-h recovery period after a 200-m front-crawl swim affects blood-gas levels, acid-base balance, and performance during a successive trial. METHODS: Fourteen national-level male swimmers (age: 21 ± 3 years, body mass (BM):77 ± 10 kg, stature: 181 ± 7 cm) performed four maximal 200-m front-crawl tests. On one of the two days, the swimmers swam two 200-m tests with a 1-h recovery break, during which they drank water (WATER); on the other day, they performed the same protocol but consumed 0.3 g min-1 NaHCO3 solution during the recovery break (NaHCO3). RESULTS: The ingestion of NaHCO3 before the second test had no effect on swim time despite a greater [ HCO 3 - ] (19.2 ± 2.3 mmol L-1) than that measured during the first test (NaHCO3) (14.5 ± 1.1 mmol L-1) and the other two tests (WATER) (12.7 ± 2.4 and 14.8 ± 1.5 mmol L-1; F = 18.554; p = 0.000) and a higher blood pH (7.46 ± 0.03) than that measured during the first test (NaHCO3) (7.39 ± 0.02) and the other two tests (WATER) (7.16 ± 0.04 and 7.20 ± 0.05); (F = 5.255; p = 0.004). An increase in blood pCO2 (0.2 ± 0.3 kPa) between both tests (NaHCO3) compared to unchanged pCO2 values (- 0.1 ± 0.3 kPa) between the other two tests (WATER) (t = - 2.984; p = 0.011; power = 0.741) was confirmed. CONCLUSIONS: NaHCO3 ingestion during the recovery period between two 200-m front-crawl time trials had a strong buffering effect that did not positively affect performance. An increase in pCO2 may have counterbalanced this impact.

Effects of structural remodelling on gill physiology.

The complex relationships between the structure and function of fish gills have been of interest to comparative physiologists for many years. Morphological plasticity of the gill provides a dynamic mechanism to reversibly alter its structure in response to changes in the conditions experienced by the fish. The best known example of gill remodelling is the growth or retraction of cell masses between the lamellae, a rapid process that alters the lamellar surface area that is exposed to the water (i.e. the functional lamellar surface area). Decreases in environmental O2 availability and/or increases in metabolic O2 demand stimulate uncovering of the lamellae, presumably to increase the capacity for O2 uptake. This review addresses four questions about gill remodelling: (1) what types of reversible morphological changes occur; (2) how do these changes affect physiological function from the gill to the whole animal; (3) what factors regulate reversible gill plasticity; and (4) is remodelling phylogenetically widespread among fishes? We address these questions by surveying the current state of knowledge of gill remodelling in fishes, with a focus on identifying gaps in our understanding that future research should consider.

Metabolic Acidosis in CKD: Pathogenesis, Adverse Effects, and Treatment Effects.

Metabolic acidosis is a frequent complication of chronic kidney disease and is associated with a number of adverse outcomes, including worsening kidney function, poor musculoskeletal health, cardiovascular events, and death. Mechanisms that prevent metabolic acidosis detrimentally promote further kidney damage, creating a cycle between acid accumulation and acid-mediated kidney injury. Disrupting this cycle through the provision of alkali, most commonly using sodium bicarbonate, is hypothesized to preserve kidney function while also mitigating adverse effects of excess acid on bone and muscle. However, results from clinical trials have been conflicting. There is also significant interest to determine whether sodium bicarbonate might improve patient outcomes for those who do not have overt metabolic acidosis. Such individuals are hypothesized to be experiencing acid-mediated organ damage despite having a normal serum bicarbonate concentration, a state often referred to as subclinical metabolic acidosis. Results from small- to medium-sized trials in individuals with subclinical metabolic acidosis have also been inconclusive. Well-powered clinical trials to determine the efficacy and safety of sodium bicarbonate are necessary to determine if this intervention improves patient outcomes.

Mechanisms and physiological relevance of acid-base exchange in functional units of the kidney.

This review discusses the importance of homeostasis with a particular emphasis on the acid-base (AB) balance, a crucial aspect of pH regulation in living systems. Two primary organ systems correct deviations from the standard pH balance: the respiratory system via gas exchange and the kidneys via proton/bicarbonate secretion and reabsorption. Focusing on kidney functions, we describe the complexity of renal architecture and its challenges for experimental research. We address specific roles of different nephron segments (the proximal convoluted tubule, the loop of Henle and the distal convoluted tubule) in pH homeostasis, while explaining the physiological significance of ion exchange processes maintained by the kidneys, particularly the role of bicarbonate ions (HCO3-) as an essential buffer system of the body. The review will be of interest to researchers in the fields of physiology, biochemistry and molecular biology, which builds a strong foundation and critically evaluates existing studies. Our review helps identify the gaps of knowledge by thoroughly understanding the existing literature related to kidney acid-base homeostasis.

The Impacts of Heat Stress on Rumination, Drinking, and Locomotory Behavior, as Registered by Innovative Technologies, and Acid-Base Balance in Fresh Multiparous Dairy Cows.

This study hypothesizes that heat stress adversely affects dairy cows, resulting in reduced rumination, altering eating and drinking behaviors, changes in their locomotory patterns, and significant variations in their acid-base balance. The aim of this study was to investigate the impacts of heat stress on rumination, drinking, and locomotory behavior, as registered by innovative technologies, and acid-base balance in fresh multiparous dairy cows. This study was conducted during the summer, from 15 June to 8 July 2023, on a Lithuanian commercial dairy farm. We assessed 350 German Holstein cows that produced an average of 11,400 kg of milk annually throughout their second and subsequent lactation periods. We used the temperature-humidity index (THI) to divide the cows under investigation into three periods: I. high HS-THI >78 (period: 15-23 June 2023); II. medium HS-THI 72-78 (period: 24-30 June 2023); and III. low HS-THI <72 (period: 1-8 July 2023). The appropriate RumiWatch sensor (RWS) parameters were assessed between 15 June 2023 and 8 July 2023. Cows were acclimatized to the rumination, drinking, and locomotory behavior parameters during the adaptation period (1-30 June 2023). The registration process started on 15 June 2023 and terminated on 8 July 2023 and was performed every hour during the 24 h day. The acid-base balance was recorded from 15 June 2023 until 8 July 2023, once per week. The cows' activity increased by 11.75% in the high HS period compared to the low HS period (p < 0.01); high mean differences were detected for rumination, which was 17.67% higher in the high HS period and 13.80% higher in the medium HS period compared to the low HS period (p < 0.01); and the change in activity was 12.82% higher in the low HS compared to the medium HS period (p < 0.01). Cows under high HS had higher blood urea nitrogen (BUN) levels compared with cows under medium HS (p < 0.01). The observed alterations in the rumination, drinking, and locomotory behaviors, in addition to the acid-base balance, highlight the multifaceted impacts of varying heat stress on the physiological and behavioral responses of dairy cows. This suggests that the utilization of advanced technologies may assist dairy farmers in effectively monitoring and controlling heat stress in cows. Additionally, regularly assessing blood urea nitrogen levels can enable farmers to modify their feeding practices, thus promoting optimal cow well-being and productivity.

The Effect of a Subsequent Dose of Dexmedetomidine or Other Sedatives following an Initial Dose of Dexmedetomidine on Electrolytes, Acid-Base Balance, Creatinine, Glucose, and Cardiac Troponin I in Cats: Part II.

The administered dose of dexmedetomidine may occasionally fail to produce the anticipated sedative effects. Therefore, a subsequent dose or administration of another sedative may enhance sedation; however, patient safety may be affected. The safety of seven different drugs administered at the following time point after an insufficient dose of dexmedetomidine was evaluated in a crossover, blind, experimental study that included six healthy adult cats. All cats received an initial dose of dexmedetomidine and a subsequent dose of either dexmedetomidine (Group DD), NS 0.9% (DC), tramadol (DT), butorphanol (DBT), buprenorphine (DBP), ketamine (DK), or midazolam (DM). Animal safety was assessed using repeated blood gas analysis and measurement of electrolytes, glucose, cardiac troponin I, and creatinine to evaluate cardiac, respiratory, and renal function. The median values of creatinine, cardiac troponin I, pH, partial pressure of carbon dioxide, potassium, and sodium did not change significantly throughout the study. Heart rate was significantly decreased in all groups after administration of the drug combinations, except for in the DK group. Respiratory rate decreased significantly after administration of the initial dose of dexmedetomidine and in the DBP and DM groups. The partial pressure of oxygen, although normal, decreased significantly after the administration of dexmedetomidine, whereas the median concentration of glucose increased significantly following the administration of dexmedetomidine. The results of our study suggest that the drug combinations used did not alter the blood parameters above normal limits, while cardiac and renal function were not compromised. Therefore, a safe level of sedation was achieved. However, the administration of dexmedetomidine reduced the partial pressure of oxygen; thus, oxygen supplementation during sedation may be advantageous. Additionally, the increase in glucose concentration indicates that dexmedetomidine should not be used in cats with hyperglycaemia, whereas the decrease in haematocrit suggests that dexmedetomidine is not recommended in anaemic cats.

Effects of low protein diets on acid-base balance, electrolyte balance, intestinal structure, and amino acid transport in piglets.

Reducing the dietary crude protein (CP) could effectively reduce pressure on protein ingredient supplies. However, few data have been reported about the extent to which CP can be reduced and whether limiting the use of soybean meal leads to electrolyte imbalance. In this experiment, using the low protein (LP) diet [2% lower than NRC (2012)], seventy-two piglets (35 days old) were randomly divided into 2 groups with 6 replicates of 6 piglets each: CON group (CP = 18.5%) and LP group (CP = 16.5%), to investigate the effect of the LP diet on electrolyte balance, acid-base balance, intestinal structure and amino acid transport in piglets. The results revealed that the LP diet decreased the average daily gain and dietary CP digestibility, and damaged the villi structure of the small intestine. Compared with the CON diet, the potassium content decreased and the chlorine content increased in the LP diet, and similar trends were shown in piglet serum. The arterial pH, pCO2, HCO3 -, and base excess of piglets in the LP group were lower than those in the CON group, while pO2 was higher than those in the CON group. Interestingly, the LP diet significantly increased the lysine content in piglet serum and significantly decreased the levels of arginine, leucine, and glutamic acid. Furthermore, the LP diet significantly affected the expression of some amino acid transport vectors (B0AT1, EAAC1, and y+LAT1). In summary, these findings suggested that the LP diet leads to acid-base imbalance, amino acid transport disorder and amino acids imbalance in piglets, and the dietary electrolyte may be a key factor in the impact of the LP diet on piglet growth performance and intestinal health.

A Comprehensive Review of Chloride Management in Critically Ill Patients.

Chloride, often overshadowed in electrolyte management, emerges as a crucial player in the physiological intricacies of critically ill patients. This comprehensive review explores the multifaceted aspects of chloride, ranging from its significance in cellular homeostasis to the consequences of dysregulation in critically ill patients. The pathophysiology of hyperchloremia and hypochloremia is dissected, highlighting their intricate impact on acid-base balance, renal function, and cardiovascular stability. Clinical assessment strategies, including laboratory measurements and integration with other electrolytes, lay the foundation for targeted interventions. Consequences of dysregulated chloride levels underscore the need for meticulous management, leading to an exploration of emerging therapies and interventions. Fluid resuscitation protocols, the choice between crystalloids and colloids, the role of balanced solutions, and individualized patient approaches comprise the core strategies in chloride management. Practical considerations, such as monitoring and surveillance, overcoming implementation challenges, and embracing a multidisciplinary approach, are pivotal in translating theoretical knowledge into effective clinical practice. As we envision the future, potential impacts on critical care guidelines prompt reflections on integrating novel therapies, individualized approaches, and continuous monitoring practices. In conclusion, this review synthesizes current knowledge, addresses practical considerations, and envisions future directions in chloride management for critically ill patients. By embracing a holistic understanding, clinicians can navigate the complexities of chloride balance, optimize patient outcomes, and contribute to the evolving landscape of critical care medicine.

The electroneutral Na+-HCO3- cotransporter NBCn1 (SLC4A7) modulates colonic enterocyte pHi, proliferation, and migration.

NBCn1 (SLC4A7) is one of the two major Na+-HCO3- cotransporters in the human colonic epithelium, expressed predominantly in the highly proliferating colonocytes at the cryptal base. Increased NBCn1 expression levels are reported in tumors, including colorectal cancer. The study explores its importance for maintenance of the intracellular pH (pHi), as well as the proliferative, adhesive, and migratory behavior of the self-differentiating Caco2BBe colonic tumor cell line. In the self-differentiating Caco2BBe cells, NBCn1 mRNA was highly expressed from the proliferative stage until full differentiation. The downregulation of NBCn1 expression by RNA interference affected proliferation and differentiation and decreased intracellular pH (pHi) of the cells in correlation with the degree of knockdown. In addition, a disturbed cell adhesion and reduced migratory speed were associated with NBCn1 knockdown. Murine colonic Nbcn1-/- enteroids also displayed reduced proliferative activity. In the migrating Caco2BBe cells, NBCn1 was found at the leading edge and in colocalization with the focal adhesion markers vinculin and paxillin, which suggests that NBCn1 is involved in the establishment of cell-matrix adhesion. Our data highlight the physiological significance of NBCn1 in modulating epithelial pH homeostasis and cell-matrix interactions in the proliferative region of the colonic epithelium and unravel the molecular mechanism behind pathological overexpression of this transporter in human colorectal cancers.NEW & NOTEWORTHY The transporter NBCn1 plays a central role in maintaining homeostasis within Caco2BBe colonic epithelial cells through its regulation of intracellular pH, matrix adhesion, migration, and proliferation. These observations yield valuable insights into the molecular mechanism of the aberrant upregulation of this transporter in human colorectal cancers.

ß3-Adrenoceptor as a new player in the sympathetic regulation of the renal acid-base homeostasis.

Efferent sympathetic nerve fibers regulate several renal functions activating norepinephrine receptors on tubular epithelial cells. Of the beta-adrenoceptors (ß-ARs), we previously demonstrated the renal expression of ß3-AR in the thick ascending limb (TAL), the distal convoluted tubule (DCT), and the collecting duct (CD), where it participates in salt and water reabsorption. Here, for the first time, we reported ß3-AR expression in the CD intercalated cells (ICCs), where it regulates acid-base homeostasis. Co-localization of ß3-AR with either proton pump H+-ATPase or Cl-/HCO3 - exchanger pendrin revealed ß3-AR expression in type A, type B, non-A, and non-B ICCs in the mouse kidney. We aimed to unveil the possible regulatory role of ß3-AR in renal acid-base homeostasis, in particular in modulating the expression, subcellular localization, and activity of the renal H+-ATPase, a key player in this process. The abundance of H+-ATPase was significantly decreased in the kidneys of ß3-AR-/- compared with those of ß3-AR+/+ mice. In particular, H+-ATPase reduction was observed not only in the CD but also in the TAL and DCT, which contribute to acid-base transport in the kidney. Interestingly, we found that in in vivo, the absence of ß3-AR reduced the kidneys' ability to excrete excess proton in the urine during an acid challenge. Using ex vivo stimulation of mouse kidney slices, we proved that the ß3-AR activation promoted H+-ATPase apical expression in the epithelial cells of ß3-AR-expressing nephron segments, and this was prevented by ß3-AR antagonism or PKA inhibition. Moreover, we assessed the effect of ß3-AR stimulation on H+-ATPase activity by measuring the intracellular pH recovery after an acid load in ß3-AR-expressing mouse renal cells. Importantly, ß3-AR agonism induced a 2.5-fold increase in H+-ATPase activity, and this effect was effectively prevented by ß3-AR antagonism or by inhibiting either H+-ATPase or PKA. Of note, in urine samples from patients treated with a ß3-AR agonist, we found that ß3-AR stimulation increased the urinary excretion of H+-ATPase, likely indicating its apical accumulation in tubular cells. These findings demonstrate that ß3-AR activity positively regulates the expression, plasma membrane localization, and activity of H+-ATPase, elucidating a novel physiological role of ß3-AR in the sympathetic control of renal acid-base homeostasis.

Adenosine in Intestinal Epithelial Barrier Function.

At the intestinal front, several lines of defense are in place to resist infection and injury, the mucus layer, gut microbiome and strong epithelial junctions, to name a few. Their collaboration creates a resilient barrier. In intestinal disorders, such as inflammatory bowel disease (IBD), barrier function is compromised, which results in rampant inflammation and tissue injury. In response to the destruction, the intestinal epithelium releases adenosine, a small but powerful nucleoside that functions as an alarm signal. Amidst the chaos of inflammation, adenosine aims to restore order. Within the scope of its effects is the ability to regulate intestinal epithelial barrier integrity. This review aims to define the contributions of adenosine to mucus production, microbiome-dependent barrier protection, tight junction dynamics, chloride secretion and acid-base balance to reinforce its importance in the intestinal epithelial barrier.

The Effects of a Carbohydrate Hydrogel System for the Delivery of Bicarbonate Mini-Tablets on Acid-Base Buffering and Gastrointestinal Symptoms in Resting Well-trained Male Cyclists.

BACKGROUND: A new commercially available sodium bicarbonate (SB) supplement claims to limit gastrointestinal (GI) discomfort and increase extracellular buffering capacity. To date, no available data exists to substantiate such claims. Therefore, the aim of this study was to measure blood acid-base balance and GI discomfort responses following the ingestion of SB using the novel "Bicarb System" (M-SB). Twelve well-trained male cyclists completed this randomised crossover designed study. Maximal oxygen consumption was determined in visit one, whilst during visits two and three participants ingested 0.3 g∙kg-1 BM SB using M-SB (Maurten, Sweden) or vegetarian capsules (C-SB) in a randomised order. Finger prick capillary blood samples were measured every 30 min for pH, bicarbonate (HCO3-), and electrolytes (potassium, chloride, calcium, and sodium), for 300 min. Visual analogue scales (VAS) were used to assess GI symptoms using the same time intervals. RESULTS: Peak HCO3- was 0.95 mmol∙L-1 greater following M-SB (p = 0.023, g = 0.61), with time to peak HCO3- achieved 38.2 min earlier (117 ± 37 vs. 156 ± 36 min; p = 0.026, r = 0.67) and remained elevated for longer (p = 0.043, g = 0.51). No differences were observed for any electrolytes between the conditions. Aggregated GI discomfort was reduced by 79 AU following M-SB (p < 0.001, g = 1.11), with M-SB reducing stomach cramps, bowel urgency, diarrhoea, belching, and stomach-ache compared to C-SB. CONCLUSIONS: This is the first study to report that M-SB can increase buffering capacity and reduce GI discomfort. This presents a major potential benefit for athletes considering SB as an ergogenic supplement as GI discomfort is almost eliminated. Future research should determine if M-SB is performance enhancing.

The novel 'Bicarb System' (M-SB) reduced, and almost eliminated the gastrointestinal (GI) discomfort compared to vegetarian capsules (C-SB). The changes in acid-base balance following ingestion of M-SB were significantly greater compared to C-SB. It is unkown if this would translate to increased performance benefits, however, and the next step therefore is to determine the performance responses from M-SB. The increase in HCO₃⁻ was sustained >5 mmol L⁻¹ HCO₃⁻ for longer with M-SB ingestion versus C-SB. This might suggest there is an "ergogenic window", and ingestion timing could therefore be flexible prior to exercise.

The influence of substituting dietary peptide-bound with free amino acids on nitrogen metabolism and acid-base balance of broiler chickens depends on asparagine and glutamine supply.

Reducing dietary crude protein (CP) concentration while maintaining adequate amino acid (AA) supply by free AA inclusion can contribute to attenuate the negative environmental effects of animal farming. This study investigated upper limits of dietary free AA inclusions without undesirable effects including the dependence on asparagine (Asn) and glutamine (Gln) supply. Ten broilers were allocated to sixty-three metabolism units each and offered nine experimental diets from day (d) 7-21 (n 7). One diet (167 g CP/kg) contained 80 g soya protein isolate (SPI)/kg. In the other diets, 25, 50, 75 and 100 % of the digestible AA from SPI were substituted with free AA. Digestible Asn+aspartic acid (Asp) and Gln+glutamic acid (Glu) were substituted with Asp/Glu or 50/50 mixes of Asp/Asn and Glu/Gln, respectively. Total excreta were collected from d 11-14 and from d 18-21. Growth and nitrogen accretion were unaffected by 25 and 50 % substitution without and with free Asn/Gln, respectively, but decreased at higher substitution (P ≤ 0·024). Circulating concentrations of Asp, Glu and Gln were unaffected by treatment, while Asn decreased at substitution higher than 50 % when Asn/Gln were not provided (P ≤ 0·005). Blood gas analysis on d 21 indicated a compensated metabolic acidosis at substitution higher than 50 and 75 % without and with free Asn/Gln, respectively (P ≤ 0·017). Results suggest that adding Asn/Gln increased an upper limit for proportion of dietary free AA from 10 to 19 % of dietary CP and enabled higher free AA inclusion without affecting the acid-base balance.

Water, mineral, and blood acid-base balance in calves with naturally occurring diarrhea receiving two alternative oral rehydration solutions or a placebo.

Quantifying the water and mineral losses in feces is essential to determine the optimal composition of oral rehydration solutions (ORS) for diarrheic animals. In a randomized complete block design, this study evaluated water, mineral, and blood acid-base balance of calves with naturally occurring diarrhea receiving ORS or a placebo. On d 0, 45 calves (age: 18 ± 3.2 d; mean ± SD) were selected based on the presence of visual signs of diarrhea, such as dirty tail or wet feces, along with clinical symptoms evaluated by measuring the skin turgor and the degree of enophthalmos. On d 1, calves were divided into blocks of 3 animals based on blood base excess (BE) measured at 0900 h, and within each block, calves were randomly assigned to 1 of 3 treatments (15 calves per treatment) including (1) a hypertonic ORS (HYPER; Na+ = 110 mmol/L; 370 mOsm/kg; strong ion difference [SID] = 60 mEq/L), (2) a hypotonic ORS with low Na+ (HYPO; Na+ = 77 mmol/L; 278 mOsm/kg; SID = 71 mEq/L), and (3) a placebo consisting of lukewarm water with 5 g/L of whey powder (CON). Milk replacer (MR) was fed through teat buckets twice daily at 0630 h and 1700 h in 2 equally sized meals of 2.5 L from d 1 to 3 and of 3.0 L on d 4 and 5. Treatments consisting of 2.0 L lukewarm solutions were administered between milk meals from d 1 to 3 at 1200 h and 2030 h through teat buckets. Refusals of MR and treatments were recorded daily, and blood samples were collected from the jugular vein once daily at arrival in the afternoon of d 0 and at 0900 h from d 1 to 5 after arrival. Urine and feces were collected quantitatively over a 48-h period from 1200 h on d 1 to 1200 h on d 3, and a representative sample of each 24-h period was stored. In addition, the volume of extracellular fluid was evaluated on d 2 by postprandial sampling over a 4-h period relative to the injection of sodium thiosulfate at 1300 h. Total daily fluid intake (MR, treatment, and water) from d 1 to 3 was greater in HYPER (LSM ± SEM; 8.9 ± 0.36 L/d) and HYPO (7.8 ± 0.34 L/d) than in CON (6.6 ± 0.34 L/d). This resulted in a greater water balance (water intake - fluid output in urine and feces) in calves receiving ORS (59.6 ± 6.28 g/kg BW per 24 h vs. 39.6 ± 6.08 g/kg BW per 24 h). Fecal Na+ losses were greater in HYPER than in the other treatments (81 ± 12.0 mg/kg BW per 24 h vs. 24 ± 11.8 mg/kg BW per 24 h). Blood pH was higher in HYPO (7.41 ± 0.016) than CON (7.35 ± 0.016) over the 5 monitoring days, whereas HYPER (7.37 ± 0.017) did not differ with other treatments. In this experimental model, diarrheic calves were likely unable to absorb the high Na+ load from HYPER, resulting in greater Na+ losses in feces, which might have impaired the alkalinizing capacity of HYPER. In contrast, HYPO significantly sustained blood acid-base balance compared with CON, whereas HYPER did not. This suggests that low tonicity ORS with a high SID are more suitable for diarrheic calves.

Acid base homeostasis and serum bicarbonate concentration in syndrome of inappropriate anti-diuretic hormone secretion (SIADH) with hyponatremia.

The Syndrome of Inappropriate ADH secretion (SIADH) presents with excess ADH release caused by a range of conditions; including pneumonia, brain tumors, certain lung cancers, and diseases of the hypothalamus. It presents with significant reduction in both sodium and chloride concentrations in the blood. However, reports examining the acid base status indicate a normal serum bicarbonate concentration and systemic acid base homeostasis. The mechanisms for the absence of abnormalities in acid base homeostasis remain speculative. This mini review is highlighting the recent advances in renal molecular physiology to provide answers for the maintenance of acid base status and serum bicarbonate in a physiological range.

A Comparative Kidney Transcriptome Analysis of Bicarbonate-Loaded insrr-Null Mice.

The maintenance of plasma pH is critical for life in all organisms. The kidney plays a critical role in acid-base regulation in vertebrates by controlling the plasma concentration of bicarbonate. The receptor tyrosine kinase IRR (insulin receptor-related receptor) is expressed in renal ß-intercalated cells and is involved in alkali sensing due to its ability to autophosphorylate under alkalization of extracellular medium (pH > 7.9). In mice with a knockout of the insrr gene, which encodes for IRR, urinary bicarbonate secretion in response to alkali loading is impaired. The specific regulatory mechanisms in the kidney that are under the control of IRR remain unknown. To address this issue, we analyzed and compared the kidney transcriptomes of wild-type and insrr knockout mice under basal or bicarbonate-loaded conditions. Transcriptomic analyses revealed a differential regulation of a number of genes in the kidney. Using TaqMan real-time PCR, we confirmed different expressions of the slc26a4, rps7, slc5a2, aqp6, plcd1, gapdh, rny3, kcnk5, slc6a6 and atp6v1g3 genes in IRR knockout mice. Also, we found that the expression of the kcnk5 gene is increased in wild-type mice after bicarbonate loading but not in knockout mice. Gene set enrichment analysis between the IRR knockout and wild-type samples identified that insrr knockout causes alterations in expression of genes related mostly to the ATP metabolic and electron transport chain processes.

Sodium L-Aspartate Supplementation Improves Repeated-Sprint Performance.

Aspartate supplementation has been reported to improve endurance performance by facilitating the tricarboxylic acid cycle flux. The present study was performed to investigate the effects of aspartate supplementation on repeated-sprint performance and blood pH. Following an overnight fast, fourteen healthy males completed three sets of 10 × 6 s maximal sprints after consuming sodium L-aspartate (ASP) or placebo (PLA), in a double-blind manner. Both supplements were taken twice on each test day (2 × 4.5 g). Exercise performance (e.g., cadence and power output) and blood variables (e.g., pH and plasma amino acid levels) were measured. The ASP trial evidenced significantly higher plasma aspartate concentration during the first (ASP, 45.3 ± 9.2 µM; PLA, 6.1 ± 0.8 µM) and the second exercise sets (ASP, 24.2 ± 4.5 µM; PLA, 6.6 ± 0.9 µM) and peak cadence during the second set (ASP, 153 ± 3 rpm; PLA, 152 ± 3 rpm) compared with the PLA trial (all p < 0.05). The peak power output during the second exercise set (ASP, 743 ± 32 W; PLA, 734 ± 31 W; p = 0.060) and the blood pH immediately before (ASP, 7.280 ± 0.020; PLA, 7.248 ± 0.016; p = 0.087) and after the third exercise set (ASP, 7.274 ± 0.019; PLA, 7.242 ± 0.018; p = 0.093) tended to be higher in the ASP than in the PLA trial. In conclusion, ASP supplementation partially improved repeated-sprint performance (peak cadence during the second exercise set). However, it did not affect the mean power output.

Effect of different hypoxic and hypobaric interventions on blood gas and erythrocyte-related indicators in rats. / ä¸åŒç¼ºæ°§å¹²é¢„å¯¹ä½ŽåŽ‹ä½Žæ°§æ¨¡åž‹é¼ è¡€æ°”åŠçº¢ç»†èƒžç›¸å ³æŒ‡æ ‡çš„å½±å“.

OBJECTIVES: To explore the effects of hypoxic and hypobaric conditions on blood gas and erythrocyte-related indicators in rats. METHODS: SD male rats were exposed to low-pressure hypoxic conditions simulating an altitude of 6500 m in a small or a large experimental cabin. Abdominal aortic blood samples were collected and blood gas indicators, red blood cells (RBCs) count, and hemoglobin (Hb) content were measured. The effects of exposure to different hypoxia times, different hypoxia modes, normal oxygen recovery after hypoxia, and re-hypoxia after hypoxia preconditioning on blood gas indicators, RBCs count and Hb content were investigated. RESULTS: The effect of blood gas indicators was correlated with the length of exposure time of hypoxia and the reoxygenation after leaving the cabin. Hypoxia caused acid-base imbalance and its severity was associated with the duration of hypoxia; hypoxia also led to an increase in RBCs count and Hb content, and the increase was also related to the time exposed to hypoxia. The effects of reoxygenation on acid-base imbalance in rats caged in a small animal cabin were more severe that those in a large experimental cabin. Acetazolamide alleviated the effects of reoxygenation after leaving the cabin. Different hypoxia modes and administration of acetazolamide had little effect on RBCs count and Hb content. Normal oxygen recovery can alleviate the reoxygenation and acid-base imbalance of hypoxic rats after leaving the cabin and improve the increase in red blood cell and hemoglobin content caused by hypoxia. The improvement of hypoxia preconditioning on post hypoxia reoxygenation is not significant, but it can alleviate the acid-base imbalance caused by hypoxia in rats and to some extent improve the increase in red blood cell and hemoglobin content caused by hypoxia. CONCLUSIONS: Due to excessive ventilation and elevated RBCs count and Hb content after hypoxia reoxygenation, oxygen partial pressure and other oxygenation indicators in hypoxic rats are prone to become abnormal, while blood gas acid-base balance indicators are relatively stable, which are more suitable for evaluating the degree of hypoxia injury and related pharmacological effects in rats.

The reduction in arterial pH with increased temperature is not affected by hyperoxia in toads (Rhinella marina) and pythons (Python molurus).

It is well established that arterial pH decreases with increased temperature in amphibians and reptiles through an elevation of arterial PCO2, but the underlying regulation remains controversial. The alphastat hypothesis ascribes the pH fall to a ventilatory regulation of protein ionisation, but the pH reduction with temperature is lower than predicted by the pKa change of the imidazole group on histidine. We hypothesised that arterial pH decreases at high, but not at low, temperatures when toads (Rhinella marina) and snakes (Python molurus) are exposed to hyperoxia. In toads, hyperoxia caused similar elevations of arterial PCO2 at 20 and 30°C, indicative of a temperature-independent oxygen-mediated drive to breathing, whereas PCO2 was unaffected by hyperoxia in snakes at 25 and 35°C. These findings do not support our hypothesis of an increased oxygen-mediated drive to breathing as body temperature increases.

Sodium bicarbonate induces alkalosis, but improves high-intensity cycling performance only when participants expect a beneficial effect: a placebo and nocebo study.

The study aimed to investigate the effects of sodium bicarbonate (NaHCO3) intake with divergent verbal and visual information on constant load cycling time-to-task failure, conducted within the severe intensity domain. Fifteen recreational cyclists participated in a randomized double-blind, crossover study, ingesting NaHCO3 or placebo (i.e., dextrose), but with divergent information about its likely influence (i.e., likely to induce ergogenic, inert, or harmful effects). Performance was evaluated using constant load cycling time to task failure trial at 115% of peak power output estimated during a ramp incremental exercise test. Data on blood lactate, blood acid-base balance, muscle electrical activity (EMG) through electromyography signal, and the twitch interpolation technique to assess neuromuscular indices were collected. Despite reduced peak force in the isometric maximal voluntary contraction and post-effort peripheral fatigue in all conditions (P < 0.001), neither time to task failure, EMG nor, blood acid-base balance differed between conditions (P > 0.05). Evaluation of effect sizes of all conditions suggested that informing participants that the supplement would be likely to have a positive effect (NaHCO3/Ergogenic: 0.46; 0.15-0.74; Dextrose/Ergogenic: 0.45; 0.04-0.88) resulted in improved performance compared to control. Thus, NaHCO3 ingestion consistently induced alkalosis, indicating that the physiological conditions to improve performance were present. Despite this, NaHCO3 ingestion did not influence performance or indicators of neuromuscular fatigue. In contrast, effect size estimates indicate that participants performed better when informed that they were ingesting an ergogenic supplement. These findings suggest that the apparently ergogenic effect of NaHCO3 may be due, at least in part, to a placebo effect.