Comparative Evaluation of 0.9% Normal Saline Versus Acetate-Gluconate-Based Balanced Solution on Acid-Base Status and Postoperative Liver Function in Donor Hepatectomy Patients.

Background Live donor liver transplantation, a widely practiced procedure, involves resecting a portion of a healthy donor's liver for transplantation. Despite advancements, it poses challenges like cardiovascular instability and electrolyte imbalances, with maintaining acid-base balance being critical. This study compares the effects of 0.9% normal saline and PlasmaLyte A® on acid-base status and postoperative liver function. Methodology This prospective observational study was conducted over one year among 40 healthy adults aged 18-60 years undergoing donor hepatectomy. Patients were alternately allocated to receive either 0.9% saline (Group 1; n = 20) or PlasmaLyte A® (Group 2; n = 20). Key parameters, including acid-base status, hemodynamic parameters, and postoperative liver function, were monitored at various intervals. Statistical analysis was performed using IBM SPSS Statistics for Windows, Version 25.0 (Released 2017; IBM Corp., Armonk, NY, USA), with appropriate statistical tests. A p-value <0.05 was considered statistically significant. Results The study included 40 patients, with 20 in each group. No significant differences were observed between the groups concerning age, gender, weight, hemodynamic parameters, and urine output. However, significant differences were found in acid-base parameters. Group 2 showed better preservation of acid-base balance with higher pH and HCO3 levels. Patients in Group 1 exhibited a significant decrease in HCO3 levels during surgery, while those in Group 2 maintained a more stable metabolic profile. Furthermore, nine patients in Group 1 required sodium bicarbonate supplementation for metabolic acidosis, compared to only three in Group 2. Postoperative liver function tests revealed no significant differences between the two groups, although a trend toward better outcomes was observed in Group 2. Conclusions PlasmaLyte A® demonstrated superior preservation of acid-base balance compared to 0.9% normal saline, with less need for bicarbonate supplementation. While liver function outcomes were similar, the balanced solution showed a trend toward better metabolic stability, suggesting it may offer safer and more effective fluid management in liver transplantation surgery.

Dynamic dosing for continuous renal replacement therapy: Service evaluation of the safety and effectiveness of titrating dose to biochemistry.

Introduction: Continuous renal replacement therapy (CRRT) dose is usually fixed and primarily weight-based. Whilst this is safe, theoretically, underdosing or overdosing may occur in those requiring acute versus maintenance CRRT respectively. We have developed a dynamic dosing protocol for CRRT which individualises and updates dosing according to biochemistry. Here we describe the protocol and compare it to a fixed dose protocol to evaluate its safety and effectiveness. Methods: We conducted a service evaluation of this novel protocol using data from consecutive non-COVID-19 admissions receiving CRRT within Barts Health NHS trust, United Kingdom (UK). Fifty admissions using the dynamic protocol were compared to historically collected data from 108 admissions who used the fixed protocol. Acute and maintenance CRRT subgroups were analysed. Results: For the dynamic protocol 49 patients were treated with 135 CRRT circuits. One patient had two admissions. Protocol compliance (compared in one ICU) was 76% (dynamic) vs 61% (fixed) (p < 0.05). For the dynamic versus fixed protocol, median CRRT lifespan censored for reasons other than clotting was: 56 h vs 58 h RCA (ns), 27 h versus 20 h heparin (ns) and 79 h versus 22 h no anticoagulation (p < 0.05). The dynamic vs fixed protocol average CRRT dose was: 30 ml/kg/h (14-57) vs 26 ml/kg/h (20-62) (p < 0.05). The dynamic protocol generated a similar rate of increase of bicarbonate in an acute phase (RCA: 0.2 mmol/l/h vs 0.21 mmol/l/h, ns) and maintained a more stable level in a maintenance phase (RCA: -0.01 mmol/l/h vs 0.07 mmol/l/h, p < 0.05). Discussion: Dynamic dosing for CRRT in this institution was safe and may lead to more tailored maintenance of biochemical homoeostasis.

Oral but Not Topical Sodium Bicarbonate Improves Repeated Sprint Performance During Simulated Soccer Match Play Exercise in Collegiate Athletes.

This study investigated the effect of oral and topical sodium bicarbonate (SB) on soccer-specific performance during simulated soccer exercise. In a block randomized, double-blind, crossover design, 10 collegiate male soccer players (stature: 181.7 ± 3.2 cm, body mass: 81.7 ± 10.5 kg) performed soccer-specific performance tests (countermovement jumps, Illinois agility, 8 × 25 m repeated sprints) throughout a 90-min soccer-specific aerobic field test (SAFT90) following 0.3 g/kg body mass SB in capsules (SB-ORAL), 0.9036 g/kg body mass PR Lotion (SB-LOTION), or placebo capsules and lotion (PLA). Soccer-specific performance tests were conducted pre-SAFT90, during half-time and post-SAFT90. Blood samples were analyzed for acid-base balance (pH; bicarbonate, HCO3-) and strong ions (sodium, Na+; potassium, K+). Average sprint times were quicker for SB-ORAL than PLA during half-time (3.7%; p = .049; g = .57) and post-SAFT90 (4.9%; p = .041; g = .66). SB-ORAL increased pH and HCO3- prewarm-up and during half-time (p < .05), and lowered K+ during half-time (p = .035) compared with PLA. SB-LOTION increased pH (p = .019) and lowered K+ (p = .012) during half-time compared with PLA. SB-LOTION increased Na+ postexercise compared with PLA (p = .008). Repeated sprint times during simulated soccer exercise improved for SB-ORAL, which might have been mechanistically underpinned by elevated blood buffering capacity and greater regulation of strong ion concentration. Consuming SB in capsules is a more effective strategy than topical SB application for improving blood buffering capacity and repeated sprint performance throughout competitive soccer matches.

Temperature effects on blood gases in embryonic American alligators (Alligator mississippiensis).

Numerous studies report on the influence of temperature on blood gases in ectothermic vertebrates, but there is merely a cursory understanding of these effects in developing animals. Animals that develop in eggs are at the mercy of environmental temperature and are expected to lack the capacity to regulate gas exchange and may regulate blood gases by means of altered conductance for gas exchange. We, therefore, devised a series of studies to characterize the developmental changes in blood gases when embryonic alligators were exposed to 25, 30 and 35 °C. To determine how blood parameters were impacted by changes in embryonic temperature, blood was sampled from the chorioallantoic membrane artery. The blood in the chorioallantoic membrane artery is a mixture of oxygen-poor and oxygen-rich blood, which based on the embryonic vascular anatomy may reflect blood that perfuses the chemoreceptors of the developing animal. Our findings indicate that following a 48 h exposure to 25 °C or 35 °C, there was a positive relationship between CAM artery blood PO2, PCO2 and glucose. However, blood pH suggests embryonic alligators lack an acute regulatory mechanism for adjusting blood pH.

Enhancing exercise performance and recovery through sodium bicarbonate supplementation: introducing the ingestion recovery framework.

Sodium bicarbonate (SB) supplementation is an ergogenic strategy for athletes competing in high-intensity exercise, but the efficacy of SB for accelerating recovery from exercise and thus improving performance during repeated bouts of exercise is not fully understood. In a similar fashion to using SB as a pre-exercise buffer, it is possible accelerated restoration of blood pH and bicarbonate following an exercise bout mechanistically underpins the use of SB as a recovery aid. Physiological mechanisms contributing to beneficial effects for SB during repeated bout exercise could be more far-reaching however, as alterations in strong ion difference (SID) and attenuated cellular stress response might also contribute to accelerated recovery from exercise. From inspection of existing literature, ingestion of 0.3 g kg-1 body mass SB ~60-90 min pre-exercise seems to be the most common dosage strategy, but there is evidence emerging for the potential application of post-exercise supplementation timing, gradual SB doses throughout a competition day, or even ingestion during exercise. Based on this review of literature, an SB ingestion recovery framework is proposed to guide athletes and practitioners on the use of SB to enhance performance for multiple bouts of exercise.

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.

Responses of the blood acid-base balance and blood plasma metabolomics of broiler chickens after change to diets with high free amino acid levels.

Free amino acids (AA) are needed to fulfill the AA requirements of broiler chickens in diets low in CP. This study investigated whether the acid-base balance and the blood plasma metabolome are affected immediately after a change to diets with high free AA levels. Male broiler chickens received a starter diet with 164 g CP/kg and 80 g soy protein isolate/kg until d 7 post-hatch. From this day on, birds were offered a diet almost identical to the starter diet (0FAA) or 2 diets with 50% (50FAA) or 100% (100FAA) of the digestible AA from soy protein isolate substituted with free AA. Blood was sampled to determine the acid-base status and for untargeted metabolomics analysis on d 0, 1, 2, 4, 7, and 14 and d 1, 7, and 14 after diet change, respectively (n = 14 birds/treatment). Compared to 0FAA, blood pH was decreased on d 4 and 7 for 100FAA and on d 4 for 50FAA (P ≤ 0.019). On d 4, 7, and 14, bicarbonate, base excess, and total carbon dioxide were lower for 100FAA than for 0FAA (P ≤ 0.006). The partial pressure of carbon dioxide was higher for 50FAA than for 0FAA on d 4 (P = 0.047). Compared to 0FAA, chloride was higher for 100FAA on d 1, 2, 4, 7, and 14, and for 50FAA on d 1, 2, and 4 (P ≤ 0.030). In the metabolomics assay, 602, 463, and 302 metabolites were affected by treatment on d 1, 7, and 14, respectively (P < 0.050), but they did not indicate that metabolic pathways were affected. Flavonoids were the most consistently affected category of metabolites. The results indicated a metabolic acidosis for 100FAA from d 4 to 7 and a respiratory acidosis for 50FAA on d 4 after diet change. These types of acidosis were compensated later on in the experiment. The metabolomics analysis did not indicate that high free AA inclusion affected metabolic pathways.

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.

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.

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 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.

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 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.

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.

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.

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.

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.