Blood Bicarbonate Research Articles

NRF2 regulates the glutamine transporter Slc38a3 (SNAT3) in kidney in response to metabolic acidosis

Expression of the glutamine transporter SNAT3 increases in kidney during metabolic acidosis, suggesting a role during ammoniagenesis. Microarray analysis of Nrf2 knock-out (KO) mouse kidney identified Snat3 as the most significantly down-regulated transcript compared to wild-type (WT). We hypothesized that in the absence of NRF2 the kidney would be unable to induce SNAT3 under conditions of metabolic acidosis and therefore reduce the availability of glutamine for ammoniagenesis. Metabolic acidosis was induced for 7 days in WT and Nrf2 KO mice. Nrf2 KO mice failed to induce Snat3 mRNA and protein expression during metabolic acidosis. However, there were no differences in blood pH, bicarbonate, pCO2, chloride and calcium or urinary pH, ammonium and phosphate levels. Normal induction of ammoniagenic enzymes was observed whereas several amino acid transporters showed differential regulation. Moreover, Nrf2 KO mice during acidosis showed increased expression of renal markers of oxidative stress and injury and NRF2 activity was increased during metabolic acidosis in WT kidney. We conclude that NRF2 is required to adapt the levels of SNAT3 in response to metabolic acidosis. In the absence of NRF2 and SNAT3, the kidney does not have any major acid handling defect; however, increased oxidative stress and renal injury may occur.

The Neurovascular Coupling Response Remains Intact During Incremental Ascent to High Altitude (4370m) in Acclimatized Healthy Volunteers

Neurovascular coupling (NVC) is the link between neuronal metabolic activity and regional cerebral blood flow. NVC is responsible for ensuring adequate delivery of nutrients (O2 and glucose) during periods of increased neuronal metabolic demand. Exposure to high‐altitude (HA) elicits ventilatory and acid‐base adjustments for maintaining blood pH. Acute exposure to HA causes hypoxic vasodilation. Hypoxia also drives a ventilatory response, inducing hypocapnia, a potent vasoconstrictor. Whether these dynamic and conflicting responses affect NVC during incremental ascent to HA is unclear.The aim of this project was to assess whether changes in arterial blood gases (ABGs) associated with ascent to HA influences the NVC response. Given that CBF is particularly sensitive to changes in PaCO2, we hypothesized that hypocapnic vasoconstriction during ascent would decrease the NVC response with ascent.10 healthy study participants (21.7±1.3 yrs, 70.46±13.65kg, mean±SD) were recruited as part of a research expedition to Everest base camp, Nepal. Resting posterior cerebral artery velocity (PCAv), ABGs (PaO2, PaCO2), SaO2, arterial blood pH and bicarbonate [HCO3−] were measured at four locations: Calgary (1045m; baseline; BL), Namche (3440m), Deboche (3820m) and Pheriche (4370m). Resting PCAv was measured using transcranial Doppler ultrasound. Arterial blood draws were taken from the radial artery and analysed using a portable blood gas/electrolyte analyser used to monitor changes in ABGs (PaCO2, PaO2, SaO2), pH and [HCO3−] during ascent. NVC was tested via visual stimulation (VS; Strobe light; 6Hz; 30sec on/off ×3). The NVC response was averaged across three VS trials at each location. NVC was quantified as the change (delta) in mean and peak PCAv from baseline, during VS.A one‐factor‐repeated measures analysis of variance (ANOVA) was used to assess for differences in baseline PCAv, NVC, ABGs, blood pH and [HCO3−] between locations. PaO2, PaCO2 and SaO2 were significantly decreased from BL at each altitude (P<0.001, P<0.016 and P<0.013, respectively). No significant differences were found for pH at any location compared to BL (P>0.05) due to reductions in arterial [HCO3−] (P<0.043). No significant differences were found in baseline PCAv between locations (P>0.05) or for mean or peak NVC responses (P>0.085 and P>0.08 respectively).As expected, incremental ascent to HA induced a state of hypoxic hypocapnia, as demonstrated by significant reductions in PaO2, SaO2 and PaCO2, whereas arterial pH was maintained via reductions in [HCO3−]. Our data suggests that NVC remains remarkably intact during incremental ascent to HA in healthy acclimatized individuals. Despite the array of superimposed stressors associated with ascent to HA, CBF and NVC regulation may be a unique function of arterial pH maintenance.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Intestinal epithelial‐specific NHE3 knockout causes metabolic acidosis

The Na+/H+ exchanger isoform 3 (NHE3) has an important role in intestinal and renal Na+ uptake and acid‐base regulation. While renal‐specific NHE3 knockout models have been successfully generated, no intestinal‐specific model has been described. Of note, renal‐specific NHE3 knockout does not result in altered blood pH or bicarbonate levels (Kidney International; 2017, 92:397–414) and conventional intestinal epithelial cell‐specific NHE3 knockout mice die shortly after birth. To determine the role of NHE3 selectively in the intestine, we generated tamoxifen (Tam)‐inducible epithelial‐specific NHE3 knockout mice (NHE3IEC‐KO) by intercrossing NHE3loxlox (control, Con) and VillinCreERT2 mice. Semiquantitative fluorescent labeling determined that application of Tam (5 days, 200 mg/kg via oral gavage) deleted NHE3 from the small intestine and colon of NHE3IEC‐KO mice, whereas labeling in the proximal tubule and thick ascending limb of the kidney was unaffected. Before Tam, Con and NHE3IEC‐KO (n=8 and 4, respectively) mice had comparable blood pH (7.4±0.01 vs 7.4±0.01), HCO3− (24.7±0.7 vs 24.6±0.6 mM), base excess (0.5±0.2 vs 0.6±0.1 mM) and Na+ concentrations (147±0.4 vs 148±0.8 mM). Two weeks after Tam, compared to Con mice, NHE3IEC‐KO mice show significant metabolic acidosis (Δ change: 0±0.01 vs −0.15±0.03, P<0.05), lower HCO3− (Δ change: 0±0.4 vs −7±1, P<0.05) and negative base excess (Δ change: 0±0.7 vs −9±2, P<0.05), whereas plasma Na+ was unaffected (Δ change: 0.5±0.6 vs −0.3±1, NS). Indirect evidence for impaired intestinal HCO3− uptake using intestinal flushes showed a significantly higher flush pH in NHE3IEC‐KO compared to Con mice (7.9±0.1 vs 7.4±0.1, P<0.05). In conclusion, we successfully generated intestinal epithelial cell‐specific NHE3 knockout mice. The mouse model will be useful to study different aspects of NHE3 in the intestine and colon. The data indicate a prominent unrecognized role of the intestine for acid‐base regulation.Support or Funding InformationNovo Nordisk Foundation, the Lundbeck Foundation, Danish Medical Research Council, NIH 1R01DK110621, APS STRIDE Undergraduate Summer Research Fellowship 1R25HL115473‐01This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Insulin receptor‐related receptor as an extracellular pH sensor regulating bicarbonate excretion

The acid‐base balance in the organism at the system level is controlled primarily by the kidneys and lungs. In the kidneys, this function is performed by the intercalated cells of two types; alpha cells excrete excess acids while beta cells excrete excess bases as bicarbonate. In a result of the biochemical analysis of the insulin receptor‐related receptor (IRR), a receptor‐like tyrosine kinase enriched in beta‐intercalated cells, we discovered its ability to activate upon the extracellular treatment with mildly alkaline media. IRR is a close homolog of the receptors of insulin and insiln‐like growth factor but cannot be activated by to their agonists whereas IRR homologs do not respond to extracellular pH changes. This pH‐sensing property of IRR is evutionary conserved from amphibians to mammals. The IRR activation by alkali resembles a typical ligand‐receptor interaction since it is dose‐dependent and saturable, specific in relation to other homologous receptors, defined by the structure of the IRR ectodomain and accompanied by its conformational changes. Mutagenesis revealed two sites in the IRR ectodomain that act synergystically to induce the receptor activation. IRR activation triggers intracellular signaling resembling the insulin receptor pathway. We obtained a panel of monoclonal antibodies against the IRR ectodomain, one of them being able to activate the receptor, and another – to inhibit its response to alkaline media. Altogether, the obtained data suggest that IRR is a cellular pH sensor. We used kcnockout mice to address IRR systemic functions. The knockout mice are viable in normal conditions but fail to excrete excees bicarbonate upon experimentally induced alkalosis. Nevertheless, the increased blood bicarbonate is compensated by CO2 retention that keeps the blood pH within the physiological range. We performed comparative analyses of knockout and wild type mice kidney and brain transcriptomes and identified statistically valid changes in the expression of several proteins, in particular, ion transporters. Also, a behavioral phenotype of the knockout mice was revealed. They appeared to be less socially active and less agressive as compared to their wild‐type littermates.Support or Funding InformationThis work was financially supported by the Russian Science Foundation (grant № 14‐50‐00131)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Responses to short‐term acid loading in proximal‐tubule‐select insulin/insulin‐like growth factor receptor dual knockout mice

Acidosis has been associated with increased renal gluconeogenesis, which in the absence of liver compensation, can lead to hyperglycemia. Acidosis leads to glutamine uptake in the proximal tubule (PT) to liberate bicarbonate and neutralize acids. The remaining carbon skeleton can be used for glucose production at this site. Whether insulin or the related hormone, insulin‐like‐growth‐factor, type 1 (IGF1), modulate these responses to acidosis is unclear. To address this, we bred mice with dual knockout (KO) of the insulin (Insr) and the Igf1r receptors from PT by Cre‐lox recombination using a γ‐glutamyl transferase promoter. KO mice had on average 40% lower expression of both Igf1r and Insr in cortex homogenates. To address the effects of acidosis, male (M) and female (F) wild‐type (WT, Cre negative) and KO (Cre positive) mice were provided ad libitum access to normal drinking water or a water‐based solution containing 1.5% NH4Cl for 7 days (n = 6/treatment/genotype/sex). Fasting (18‐hr) blood glucose was determined in a subset of mice after one week of control then acid treatment. MKO mice showed the greatest mean rise in fasting blood glucose with acid (mg/dl, delta acid‐control): −1.67 (MWT); +15.75 (MKO); −6.40 (FWT); +4.08 (FKO). Urine (24 hr) was collected in metabolic cages on days 5–6. Acid water led to a 30–64% reduction in urine volume in all groups except MWT (ml, delta acid‐control): +0.49 (MWT); −0.54 (MKO); −0.90 (FWT); −1.50 (FKO). Blood chemistry revealed greater sensitivity to acid loading in the male KO. Mean deltas (acid‐control) for blood bicarbonate, base excess, and anion gap, respectively were (mM): −5.73, −7.8, +1.24 (MWT); −8.86, −11.30, +4.67 (MKO); −7.35, −10.36, +4.74 (FWT); −1.67, −1.92, −0.6 (FKO). Western blotting for 3 rate‐limiting enzymes in gluconeogenesis conducted on the cortex from male mice revealed a significant rise in glucose‐6‐phosphatase (G6P), phosphoenolpyruvate carboxykinase (PEPCK), and fructose bisphosphatase (FBP1) in the acid drinking WT males (16–34%). In contrast, MKO mice had a significant reduction in G6P (22%) with acid water; however, FBP1 was increased by acid drinking to a greater extent (60%) in the KO, (as compared to WT, significant interaction). Overall our studies reveal a role for PT‐associated Insr and/or Igf1r signaling in regulating PT responses to an acid load and glucose homeostasis.Support or Funding InformationGeorgetown University Medical CenterGeorgetown/Howard CTSA awardThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Evaluation of capillary leakage after vasopressin resuscitation in a hemorrhagic shock model

BackgroundHemorrhagic shock (HS) is a major threat to patients with trauma and spontaneous bleeding. The aim of the study was to investigate early effects of vasopressin on metabolic and hemodynamic parameters and endothelium permeability by measuring capillary leakage compared to those of other resuscitation strategies in a HS model.MethodsForty-five Sprague-Dawley rats were randomized into five groups: S group (n = 5), sham-operated rats without shock or resuscitation; HS group (n = 10), HS and no resuscitation; RL group (n = 10), HS and resuscitation with Ringer’s lactate (RL); RLB group (n = 10), HS and resuscitation with two-third shed blood plus RL; and vasopressin group (n = 10), HS and resuscitation with RL, followed by continuous infusion of 0.04 U/kg/min vasopressin. The effects of resuscitation on hemodynamic parameters [mean arterial pressure (MAP), superior mesenteric artery blood flow (MBF), and mesenteric vascular resistances (MVR)], arterial blood gases, bicarbonate, base deficit, and lactate levels as well as on capillary leakage in the lung, ileum, and kidney were investigated. Capillary leakage was evaluated with Evans blue dye extravasation.ResultsIn the vasopressin group, the MAP was higher than in the RL and RLB groups (p < 0.001), while MBF was decreased (p < 0.001). MVR were increased only in the vasopressin group (p < 0.001). Capillary leakage was increased in the lungs of the animals in the vasopressin group compared to that in the lungs of animals in the RLB group (p < 0.05); this increase was associated with the lowest partial pressure of oxygen (p < 0.05). Conversely, decreased capillary leakage was observed with vasopressin in the ileum (p < 0.05). Increased capillary leakage was observed in the kidney in the RLB and vasopressin groups (p < 0.05). Lastly, vasopressin use was associated with higher base deficit and lactate levels when compared to the RL and RLB groups (p < 0.001).ConclusionAlthough vasopressin was proposed as a vasoactive drug for provisional hemodynamic optimization in the early phase of HS resuscitation, the overall findings of this experimental study focus on the possible critical side effects of vasopressin on metabolic parameters and endothelium permeability.

The effect of isohydric hemodialysis on the binding and removal of uremic retention solutes.

BackgroundThere is growing evidence that the accumulation of protein- bound uremic retention solutes, such as indoxyl sulfate, p-cresyl sulfate and kynurenic acid, play a role in the accelerated cardiovascular disease seen in patients undergoing chronic hemodialysis. Protein-binding, presumably to albumin, renders these solutes poor-dialyzable.We previously observed that the free fraction of indoxyl sulfate was markedly reduced at the end of hemodialysis. We hypothesized that solute binding might be pH-dependent and attributed the changes in free solute concentration to the higher serum pH observed at the end of standard hemodialysis with dialysis buffer bicarbonate concentration greater than 35 mmol/L. We observed that acidification of uremic plasma to pH 6 in vitro greatly increased the proportion of freeIS.MethodsWe tested our hypothesis by reducing the dialysate bicarbonate buffer concentration to 25 mmol/L for the initial half of the hemodialysis treatment (“isohydric dialysis”). Eight stable hemodialysis patients underwent “isohydric dialysis” for 90 minutes and then were switched to standard buffer (bicarbonate = 37mmol/L). A second dialysis, 2 days later, employed standard buffer throughout.ResultsWe found a clearcut separation of blood pH and bicarbonate concentrations after 90 minutes of “isohydric dialysis” (pH = 7.37, bicarbonate = 22.4 mmol/L) and standard dialysis (pH = 7.49, bicarbonate = 29.0 mmol/L). Binding affinity varied widely among the 10 uremic retention solutes analyzed. Kynurenic acid (0.05 free), p-cresyl sulfate (0.12 free) and indoxyl sulfate (0.13 free) demonstrated the greatest degree of binding. Three solutes (indoxyl glucuronide, p-cresyl glucuronide, and phenyl glucuronide) were virtually unbound. Analysis of free and bound concentrations of uremic retention solutes confirmed our prediction that binding of solute is affected by pH. However, in a mixed models analysis, we found that the reduction in total uremic solute concentration during dialysis accounted for a greater proportion of the variation in free concentration, presumably an effect of saturation binding to albumin, than did the relatively small change in pH produced by isohydric dialysis. The effect of pH on binding appeared to be restricted to those solutes most highly protein-bound.The solutes most tightly bound exhibited the lowest dialyzer clearances. An increase in dialyzer clearance during isohydric and standard dialyses was statistically significant only for kynurenic acid.ConclusionThese findings provide evidence that the binding of uremic retention solutes is influenced by pH. The effect of reducing buffer bicarbonate concentration (“isohydric dialysis:”), though significant, was small but may be taken to suggest that further modification of dialysis technique that would expose blood to a greater decrease in pH would lead to a greater increase the free fraction of solute and enhance the efficacy of hemodialysis in the removal of highly protein-bound uremic retention solutes.

Clinical Outcome of Urgent Thoracotomy in Patients with Penetrating and Blunt Chest Trauma: A Retrospective Survey.

In contrast to an emergency department of thoracotomy (EDT), an urgent thoracotomy (UT) is defined as a surgical thoracic intervention performed in the operating room within the first 48 hours of the patient's intensive care unit (ICU) stay. The factors affecting survival after UT are not fully understood. In this study, we retrospectively analyzed the clinical data and outcome of patients with blunt and penetrating chest injuries who underwent UT. All adult patients who had blunt or penetrating chest trauma and who underwent UT, were included in the study. All data were collected from the patients' hospital and ICU records. Forty-five patients with thoracic injuries who underwent UT during the first 48 hours of ICU stay were analyzed. Of these, 25 had penetrating chest injuries, and 20 had blunt thoracic injuries. Of the penetrating injuries, 16 were stab wounds, and 9 were gunshot wounds. Overall ICU mortality was 29% (n = 13) and was significantly higher in the blunt chest trauma group than in the penetrating trauma group (45% vs 16%; p = 0.04). Lung parenchyma injuries (lacerations and contusions) were the most common intraoperative findings in both groups. The following independent predictors of in-hospital mortality were found: an Injury Severity Score (ISS) of >40; an Acute Physiology and Chronic Evaluation II (APACHE II) score of >30; prolonged duration of UT; low body temperature on admission to the ED; abnormal arterial blood lactate, bicarbonate, and pH at the end of UT; and use of vasopressors during the first 24 hours of ICU stay. Mortality after UT was higher in patients with blunt chest trauma. The UT should be performed in both penetrating and blunt chest trauma as quickly as possible and should be limited to damage control. It also emerges that acidosis and hypothermia in chest trauma patients need to be treated extremely aggressively before, during, and after UT.

Sodium bicarbonate improves 4 km time trial cycling performance when individualised to time to peak blood bicarbonate in trained male cyclists

ABSTRACTThe aim of this study was to investigate the effects of sodium bicarbonate (NaHCO3) on 4 km cycling time trial (TT) performance when individualised to a predetermined time to peak blood bicarbonate (HCO3−). Eleven male trained cyclists volunteered for this study (height 1.82 ± 0.80 m, body mass (BM) 86.4 ± 12.9 kg, age 32 ± 9 years, peak power output (PPO) 382 ± 22 W). Two trials were initially conducted to identify time to peak HCO3− following both 0.2 g.kg−1 BM (SBC2) and 0.3 g.kg−1 BM (SBC3) NaHCO3. Thereafter, on three separate occasions using a randomised, double-blind, crossover design, participants completed a 4 km TT following ingestion of either SBC2, SBC3, or a taste-matched placebo (PLA) containing 0.07 g.kg−1 BM sodium chloride (NaCl) at the predetermined individual time to peak HCO3−. Both SBC2 (−8.3 ± 3.5 s; p < 0.001, d = 0.64) and SBC3 (−8.6 ± 5.4 s; p = 0.003, d = 0.66) reduced the time to complete the 4 km TT, with no difference between SBC conditions (mean difference = 0.2 ± 0.2 s; p = 0.87, d = 0.02). These findings suggest trained cyclists may benefit from individualising NaHCO3 ingestion to time to peak HCO3− to enhance 4 km TT performance.

Short-term aerobic exercise does not change kidney function in students of Nnamdi Azikiwe University, Nigeria

BackgroundExercise has been known to have beneficial effects on human health. The kidneys play an important role in regulating acid-base and water-electrolyte balance disturbances induced by exercise. The objective of this study was to investigate the effect of short term aerobic exercise (volleyball training) on the kidney function of apparently healthy individuals. MethodsAn experimental study of pre-post test design was conducted involving 41 amateur volleyball players, comprising 22 males and 19 females. They were randomly divided into seven different teams. Each team trained for at least 45 minutes for four consecutive days for two weeks. Both pre-and post-exercise blood pressure (BP) was measured using an automatic blood pressure measuring device OMRON 907 (OMRON, Hoofddorp, Netherlands). Likewise, both pre- and post-exercise blood samples were collected into lithium heparin tubes and centrifuged at 3000 rpm for 10 minutes and the plasma separated into plain tubes. Electrolytes were analysed using ion selective electrode machine (SFRI 4000, Germany), urea using modified Berthelot method, creatinine using Jaffe-Slot method and uric acid using the uricase method and estimated glomerular filtration state (eGFR) was calculated using the Modification of Diet in Renal Disease (MDRD) formula. ResultsThe mean levels of pre- and post-exercise systolic blood pressure, creatinine, urea, sodium, potassium, chloride, bicarbonate and eGFR did not differ significantly (p&gt;0.05). However, serum uric acid was significantly increased (p&lt;0.05), while diastolic BP significantly decreased after exercise (p&lt;0.05).ConclusionThe study showed that short-term moderate intensity aerobic exercise does not have any significant effect on the renal functions.

The Reproducibility of 4-km Time Trial (TT) Performance Following Individualised Sodium Bicarbonate Supplementation: a Randomised Controlled Trial in Trained Cyclists

BackgroundIndividual time to peak blood bicarbonate (HCO3−) has demonstrated good to excellent reproducibility following ingestion of both 0.2 g kg−1 body mass (BM) and 0.3 g kg−1 BM sodium bicarbonate (NaHCO3), but the consistency of the time trial (TT) performance response using such an individualised NaHCO3 ingestion strategy remains unknown. This study therefore evaluated the reproducibility of 4-km TT performance following NaHCO3 ingestion individualised to time to peak blood bicarbonate.MethodsEleven trained male cyclists completed five randomised treatments with prior ingestion of 0.2 g kg−1 (SBC2) or 0.3 g kg−1 BM (SBC3) NaHCO3, on two separate occasions each, or a control trial entailing no supplementation. Participants completed a 4-km cycling TT on a Velotron ergometer where time to complete, power and speed were measured, whilst acid-base blood parameters were also recorded (pH and blood bicarbonate concentration HCO3−) and lactate [La−].ResultsAlkalosis was achieved prior to exercise in both SBC2 and SBC3, as pH and HCO3− were greater compared to baseline (p < 0.001), with no differences between treatments (p > 0.05). The reproducibility of the mean absolute change from baseline to peak in HCO3− was good in SBC2 (r = 0.68) and excellent in SBC3 (r = 0.78). The performance responses following both SBC2 and SBC3 displayed excellent reproducibility (r range = 0.97 to 0.99).ConclusionsResults demonstrate excellent reproducibility of exercise performance following individualised NaHCO3 ingestion, which is due to the high reproducibility of blood acid-base variables with repeat administration of NaHCO3. Using a time to peak HCO3- strategy seems to cause no dose-dependent effects on performance for exercise of this duration and intensity; therefore, athletes may consider smaller doses of NaHCO3 to mitigate gastrointestinal (GI) discomfort.

The dynamics of the metabolism of acetate and bicarbonate associated with use of hemodialysates in the ABChD trial: a phase IV, prospective, single center, single blind, randomized, cross-over, two week investigation

BackgroundIn the United States, hemodialysis (HD) is generally performed via a bicarbonate dialysate. It is not known if small amounts of acid used in dialysate to buffer the bicarbonate can meaningfully contribute to overall buffering administered during HD. We aimed to investigate the metabolism of acetate with use of two different acid buffer concentrates and determine if it effects blood bicarbonate concentrations in HD patients.MethodsThe Acid-Base Composition with use of hemoDialysates (ABChD) trial was a Phase IV, prospective, single blind, randomized, cross-over, 2 week investigation of peridialytic dynamics of acetate and bicarbonate associated with use of acid buffer concentrates. Eleven prevalent HD patients participated from November 2014 to February 2015. Patients received two HD treatments, with NaturaLyte® and GranuFlo® acid concentrates containing 4 and 8 mEq/L of acetate, respectively. Dialysate order was chosen in a random fashion. The endpoint was to characterize the dynamics of acetate received and metabolized during hemodialysis, and how it effects overall bicarbonate concentrations in the blood and dialysate. Acetate and bicarbonate concentrations were assessed before, at 8 time points during, and 6 time points after the completion of HD.ResultsData from 20 HD treatments for 11 patients (10 NaturaLyte® and 10 GranuFlo®) was analyzed. Cumulative trajectories of arterialized acetate were unique between NaturaLyte® and GranuFlo® (p = 0.003), yet individual time points demonstrated overlap without remarkable differences. Arterialized and venous blood bicarbonate concentrations were similar at HD initiation, but by 240 min into dialysis, mean arterialized bicarbonate concentrations were 30.2 (SD ± 4.16) mEq/L in GranuFlo® and 28.8 (SD ± 4.26) mEq/L in NaturaLyte®. Regardless of acid buffer concentrate, arterial blood bicarbonate was primarily dictated by the prescribed bicarbonate level. Subjects tolerated HD with both acid buffer concentrates without experiencing any related adverse events.ConclusionsA small fraction of acetate was delivered to HD patients with use of NaturaLyte® and GranuFlo® acid buffers; the majority of acetate received was observed to be rapidly metabolized and cleared from the circulation. Blood bicarbonate concentrations appear to be determined mainly by the prescribed concentration of bicarbonate.Trial registrationThis trial was registered on ClinicalTrials.gov on 11 Dec 2014 (NCT02334267).

A short-term supranutritional vitamin E supplementation alleviated respiratory alkalosis but did not reduce oxidative stress in heat stressed pigs.

ObjectiveHeat stress (HS) triggers oxidative stress and respiratory alkalosis in pigs. The objective of this experiment was to study whether a short-term supranutritional amount of dietary vitamin E (VE) can mitigate oxidative stress and respiratory alkalosis in heat-stressed pigs.MethodsA total of 24 pigs were given either a control diet (17 IU/kg VE) or a high VE (200 IU/kg VE; HiVE) diet for 14 d, then exposed to thermoneutral (TN; 20°C, 45% humidity) or HS (35°C, 35% to 45% humidity, 8 h daily) conditions for 7 d. Respiration rate and rectal temperature were measured three times daily during the thermal exposure. Blood gas variables and oxidative stress markers were studied in blood samples collected on d 7.ResultsAlthough HiVE diet did not affect the elevated rectal temperature or respiration rate observed during HS, it alleviated (all p<0.05 for diet×temperature) the loss of blood CO2 partial pressure and bicarbonate, as well as the increase in blood pH in the heat-stressed pigs. The HS reduced (p = 0.003) plasma biological antioxidant potential (BAP) and tended to increase (p = 0.067) advanced oxidized protein products (AOPP) in the heat-stressed pigs, suggesting HS triggers oxidative stress. The HiVE diet did not affect plasma BAP or AOPP. Only under TN conditions the HiVE diet reduced the plasma reactive oxygen metabolites (p<0.05 for diet× temperature).ConclusionA short-term supplementation with 200 IU/kg VE partially alleviated respiratory alkalosis but did not reduce oxidative stress in heat-stressed pigs.

123 A COMPARISON STUDY BETWEEN PRISMASOL SOLUTION AND SELF-IMPROVISED REGIME USING NORMAL SALINE, HARTMANN SOLUTION AND DEXTROSED BASED LACTATE SOLUTION IN CONTINUOUS RENAL REPLACEMENT THERAPY

NMRR-16-694-29424 Category: RRT Technique Characteristics Presenter: Dr KENG-HEE KOH Keyword: Prismasol; self-improvised regime; CRRT Corresponding Author: Koh Keng Hee (email: [email protected]) Continuous Renal Replacement Therapy (CRRT) for critically ill and hemodynamically unstable patients with Primasol solutions are well established regime. We used self-improvised regime as a substitute of prismasol solution after finishing stock of prismasol. Our self improvised regime utilizes normal saline, dextrose based lactate solution, hartmann solution and bicarbonate infusion. To compare the survival rate of self-revised CRRT compared to conventional CRRT. To compare blood pressure, carbon dioxide and bicarbonate retention, risk of hypoglycemia and duration of assisted ventilation with different CRRT regime. All adult cases with history of admission to intensive care unit and had undergone CVVH from January 2016 till April 2017 were identified and a retrospective study is performed. In this study, 72 patients were admitted to intensive care unit and undergone CRRT between January 2016 and April 2017. We only managed to retrieve 52 medical case notes from the medical record unit. There were 36 males and 16 females in this study with the median age of 54 years old. Majority of the patients (n=41,78.9%) were having sepsis, remaining of the patients was diagnosed to have intracranial bleeding (n=4, 7.7%), perforated viscus(n=3, 5.8%), polytrauma (n=2, 3.9%) and others. Out of the 40 patients who have survived more than 24 hours, 22 and 18 of them received prismasol and self-revised regime respectively. Comparisons of the outcome show that there was no difference in regards to bicarbonate level, blood pressure measurement nor risk of hypoglycemia in both group (Table 1). It showed that mean carbon dioxide level was higher in the prismasol group (mean=51.0mmHg/kPa) than the self-revised group (mean=42.7mmHg/kPa) though it was not statistically significant. Nevertheless, there was not much difference in terms of assisted ventilation duration with mean reading of 8 days and 10 days respectively. Overall, there were 19/24 subjects (79%) died in the prismasol group and 24/28 subjects (86%) died in the second group (p=0.716). Both cohorts have no differences in term of Sequential Organ Failure Assessment (SOFA) score, age, Hb and albumin levels. Although initial urea level is higher in prismasol versus self-improvised regime, adjusted univariate analysis (of survived versus fatal patients) followed by multivariate logistic regression shows that the both CRRT regime did not have differences in survival. In these cohorts, there is no much difference between prismasol and self-improvised regime group in terms of survival rate and pCO2 retention, or risk of hypoglycemia. In case of resources limitation, self improvised regime is a viable option but one need to perform surveillance to ensure acceptable survival outcome.Table 1Comparison of Outcomes between Prismasol regime and Self-improvised regimePrismasol regimeSelf-improvised regimep-valueSystolic Blood pressure (mmHg)Pre-CRRT115±21118±180.663Post-CRRT115±19125±160.076Bicarbonate level (mmol/L)Pre-CRRT12.8±4.411.3±4.70.303Post-CRRT17.3±4.815.1±5.10.135Glucose level (mmol/L)Pre-CRRT10.5±5.09.5±5.20.535Post-CRRT8.8±3.38±2.90.432Carbon dioxide level (mmHg/kPa)Pre-CRRT43.8±12.933.2±15.30.022Post-CRRT51±42.742.3±14.90.932Duration of assisted ventilation after CRRT initiation (days)8±610±90.411mean ± standard deviation are shown and comparison is with t-test.Note: Post level was taken a day after CRRT commencement Open table in a new tab

142 TIMING OF NEPHROLOGY REFERRAL AND OUTCOME IN ACUTE KIDNEY INJURY PATIENTS RECEIVING CONTINUOUS RENAL REPLACEMENT THERAPY

Category: Epidemiology and Outcomes from AKI Presenter: Dr ASIAH USAMAH Keywords: Acute kidney injury, continuous renal replacement therapy, timing of referral Timing of nephrology referral in critically ill acute kidney injury patients is a subject of debate. Some studies have found that late nephrology referral is associated with poor prognosis. No consensus exists on the best timing of nephrology consult and initiation of CRRT. To determine the factors and outcome in relation to timing of nephrology referral in acute kidney injury (AKI) patients receiving continuous renal replacement therapy (CRRT). This is a retrospective study involving all AKI patients aged more than 18 years old receiving CRRT in ICU, HKL from October 2016 till April 2017. A total of 107 patients were screened and 68 patients were included in the study. Patients were divided into 2 categories based on timing of referral from onset of AKI. Early referral is defined as referral less than 48 hours while late referral is more than 48 hours. AKI is defined as per KDIGO guideline. Data were collected from ICU local database and analysed using SPSS version 20. Categorical and demographic data were expressed as frequency (n) and percentage (%), whilst continuous variables was expressed as mean and standard deviation (SD). Sixty eight patients, comprising 51 early referral and 17 late referral were analysed. Patients who were referred late had higher mortality (n=15, 88.2%) compared to early referral group (n=35, 15.7%, p=0.22). Patients who were in the late referral group also had longer length of stay, 12days (3.5-22) compared to patients in early referral group, 4 days (2-10), p=0.049. There were no significant difference in blood urea, serum creatinine, serum lactate, bicarbonate, serum potassium and urine output volume at referrals in both groups. Late referral group had higher mortality, albeit statistically not significant most likely due to small sample size. This study did not include disease severity as a confounding factor for mortality.

The effect of air pollution on diurnal variation of performance in anaerobic tests, cardiovascular and hematological parameters, and blood gases on soccer players following the Yo–Yo Intermittent Recovery Test Level-1

ABSTRACTThis study aimed to investigate the effect of air pollution on diurnal variation of performance in anaerobic tests, cardiovascular and hematological parameters, and blood gases on soccer players following the Yo–Yo Intermittent Recovery Test Level-1 (YYIRT1). In a randomized order, 11 healthy soccer players (mean age: 21.8 [range: 20–24] years; height: 178.00 [range: 1.64–1.83] cm; body mass index [BMI]: 23.57 [range: 20.45–28.03] kg.m−2) performed a YYIRT1 at two different times of day (TOD) (08:00 h and 18:00 h) in two areas (i.e. polluted (PA) and non-polluted (NPA)) with a recovery period of ≥ 72 h in between, to determine the maximal oxygen uptake (VO2max). In each test session: resting oral temperature is measured, anaerobic performances (pre- and post-YYIRT1) were performed, cardiovascular parameters and blood samples were collected at: rest, 3 min and 60 min after the YYIRT1, to assess blood gases and hematological parameters. Our results showed that, agility performance, VO2max, red blood cells (RBC), hemoglobin (Hb), pH, and bicarbonate levels (HCO3−) decrease significantly (p < 0.001) following the YYIRT1 in PA compared to NPA. Likewise, the heart rate (HR), systolic blood pressure (SBP), platelets (PLT), white blood cells (WBC), neutrophiles (NEUT), lymphocytes (LYM), and partial pressure of CO2 levels (PvCO2) were significantly higher (p < 0.001) in PA. This effect was slightly accentuated at 18:00 h for some parameters (i.e. Agility, HCO3−, HR, PvCO2, RBC, SBP). However, performances of sprint and Sargent jump test (SJT), oral temperature, rate of perceived exertion scales (RPE), partial pressure of O2 (PvO2), diastolic blood pressure (DBP), and monocytes (MON) were not affected by pollution (p > 0.05). In conclusion, pollution seems to be critical for health stability and performance in response to YYIRT1 especially in the evening and the winter season. Therefore, coaches and athletes should draw attention to the potential importance of land use planning in their training sessions and competitions in the morning in polluted area to minimize the risk of pollution exposure.

Ingestion of Sodium Bicarbonate (NaHCO3) Following a Fatiguing Bout of Exercise Accelerates Postexercise Acid-Base Balance Recovery and Improves Subsequent High-Intensity Cycling Time to Exhaustion.

This study evaluated the ingestion of sodium bicarbonate (NaHCO3) on postexercise acid-base balance recovery kinetics and subsequent high-intensity cycling time to exhaustion. In a counterbalanced, crossover design, nine healthy and active males (age: 23 ± 2 years, height: 179 ± 5 cm, body mass: 74 ± 9 kg, peak mean minute power (Wpeak) 256 ± 45 W, peak oxygen uptake (V̇O2peak) 46 ± 8 ml.kg-1.min-1) performed a graded incremental exercise test, two familiarization and two experimental trials. Experimental trials consisted of cycling to volitional exhaustion (TLIM1) at 100% WPEAK on two occasions (TLIM1 and TLIM2) interspersed by a 90 min passive recovery period. Using a double-blind approach, 30 min into a 90 min recovery period participants ingested either 0.3 g.kg-1 body mass sodium bicarbonate (NaHCO3) or a placebo (PLA) containing 0.1 g.kg-1 body mass sodium chloride (NaCl) mixed with 4 ml.kg-1 tap water and 1 ml.kg-1 orange squash. The mean differences between TLIM2 and TLIM1 was larger for PLA compared with NaHCO3 (-53 ± 53 vs. -20 ± 48 s; p = .008, d = 0.7, CI =-0.3, 1.6), indicating superior subsequent exercise time to exhaustion following NaHCO3. Blood lactate [Bla-] was similar between treatments post TLIM1, but greater for NaHCO3 post TLIM2 and 5 min post TLIM2. Ingestion of NaHCO3 induced marked increases (p < .01) in both blood pH (+0.07 ± 0.02, d = 2.6, CI = 1.2, 3.7) and bicarbonate ion concentration [HCO3-] (+6.8 ± 1.6 mmo.l-1, d = 3.4, CI = 1.8, 4.7) compared with the PLA treatment, before TLIM2. It is likely both the acceleration of recovery, and the marked increases of acid-base after TLIM1 contributed to greater TLIM2 performance compared with the PLA condition.

Effect of handling intensity at the time of transport for slaughter on physiological response and carcass characteristics in beef cattle fed ractopamine hydrochloride.

The effects of handling intensity on the physiological response and carcass characteristics of feedlot cattle fed ractopamine hydrochloride were evaluated at the time of transport to slaughter. Eighty steers (BW = 668 ± 36 kg) representing 10 lots of similar breed, frame size, and degree of finish were blocked by lot, stratified by weight, and randomly assigned to 1 of 2 handling intensities (HI) over a 1,600 m dirt alley course: 1) low-stress handling (LSH) or 2) high-stress handling (HSH). For the LSH treatment, 4 penmates were kept at a walk with the use of a lead rider. For the HSH treatment, 4 penmates were kept at a minimum of a trot and received 2 applications of an electric prod (approximately 1 s per impulse) at 2 separate instances: first in the alley before post-handling sampling, and again during loading for transportation to the abattoir. Behavioral observations and physical indicators of stress were recorded a minimum of 1 h before handling (baseline), immediately after handling (POSTHAND), and while in lairage after a 200 km transport to the abattoir. Vital parameters were recorded at baseline and POSTHAND. Venous blood samples were collected via jugular venipuncture at baseline and POSTHAND, and mixed arterial and venous blood samples were collected during exsanguination at slaughter. Muscle tremors tended to be more prevalent in HSH cattle at POSTHAND ( = 0.10). The HSH cattle tended to have greater POSTHAND heart rate ( = 0.08); however, there was no effect of HI on POSTHAND respiration rate or rectal temperature ( 0.34). The HSH cattle had greater lactate, epinephrine, norepinephrine, cortisol, and glucose concentrations at POSTHAND ( ≤ 0.02). Additionally, HSH cattle had lower POSTHAND blood pH, bicarbonate, base excess, and partial pressure carbon dioxide ( < 0.0001). Bicarbonate concentrations were greater in HSH cattle at slaughter ( = 0.05); however, there were no differences between HI treatments for the remaining blood variables ( 0.11). Concentrations of stress hormones and CK were significantly greater at slaughter relative to baseline and POSTHAND for both LSH and HSH cattle ( < 0.001). These findings suggest cattle trotted without a lead rider develop metabolic acidosis, and illustrate the importance of low-stress handling at the time of transport for slaughter. Further research is warranted to develop strategies to mitigate stress at the time of transport and ensure the welfare of beef cattle presented to abattoirs.

Nucleated Red Blood Cells as a Marker of Acute and Chronic Fetal Hypoxia in a Rat Model.

ObjectiveTo examine the relationship between duration of fetal hypoxia, nucleated red blood cell (NRBC) count, and fetal growth.MethodsPregnant rats were exposed to a severe hypoxia (9.5%–10% O2) for varying time intervals (2, 6, 12, 24, 48, and 120 hours; n=4 for each time interval) immediately prior to delivery at term. Normoxic controls were exposed to room air (21% O2) and matched for all other study variables (n=4 rats for each time interval). Pups were delivered via hysterotomy while maintaining exposure gas concentrations. Blood gas analysis and NRBC counts were performed, and fetal body and liver weights were recorded. Student’s t test and simple regression were used for statistical analysis.ResultsAs the duration of hypoxia increased, fetal weight, liver weight, blood bicarbonate, and base excess levels decreased significantly; concomitantly, NRBC counts increased. This increase in NRBCs became statistically significant after 24 hours of exposure. After 48 hours of hypoxia there was a 2.5-fold rise in NRBC count, and after 120 hours of hypoxia there was a 4.5-fold rise in NRBC count over control levels. After 12 or more hours of hypoxia, fetal body weights were significantly reduced; 120 hours of hypoxia resulted in a 35% reduction in fetal body weight, a 34% reduction in fetal liver weight, and 356% increase in NRBC count.ConclusionIn a pregnant rat model, chronic maternal hypoxia (≥24 hours) results in a significant increase in fetal NRBC counts as well as reduced fetal body weight and organ growth.

Similarity of osmoregulatory capacity in coastal and inland alligator gar

The alligator gar Atractosteus spatula is a primitive fish species, occupying a wide range of temperature and salinity habitats. Long-distance movements are limited, leading to genetic differentiation between inland and coastal populations. Unknown is whether physiological capacity differs between geographically separated populations, particularly for traits important to osmoregulation in saline environments. Alligator gar from inland and coastal populations were reared in a similar environment and exposed to temperature (10, 30°C) and salinity (0, 20ppt) extremes to determine whether iono- and osmoregulatory ability differed between populations. There were few differences in osmoregulatory ability between populations, with similar gill, blood and gastrointestinal tract osmoregulatory parameters. Blood plasma osmolality, ion concentrations, intestinal pH and bicarbonate base concentrations, intestinal fluid osmolality, ion concentrations and gill Na+, K+-ATPase (NKA) activity were similar between populations. Notably, gar from both populations did not osmoregulate well at low temperature and high salinity, with elevated plasma osmolality and ion concentrations, low gill NKA, and little evidence of gastrointestinal tract contribution to ionic and base regulation based on a lack of intestinal fluid and low base content. Therefore, the hypothesis that coastal gar would have improved osmotic regulatory ability in saline environments as compared to inland alligator gar was not supported, suggesting physiological capacity may be retained in primitive species possibly due to its importance to their persistence through time.