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Coral calcification is intricately linked to the chemical composition of the fluid in the extracellular calcifying medium (ECM), which is situated between the calcifying cells and the skeleton. Here we demonstrate that the acid-base sensing enzyme soluble adenylyl cyclase (sAC) is expressed in calcifying cells of the coral Stylophora pistillata. Furthermore, pharmacological inhibition of sAC in coral microcolonies resulted in acidification of the ECM as estimated by the pH-sensitive ratiometric indicator SNARF, and decreased calcification rates, as estimated by calcein labeling of crystal growth. These results indicate that sAC activity modulates some of the molecular machinery involved in producing the coral skeleton, which could include ion-transporting proteins and vesicular transport. To our knowledge this is the first study to directly demonstrate biological regulation of the alkaline pH of the coral ECM and its correlation with calcification., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Sodium-glucose co-transporter 2 (SGLT2) inhibitors have been reported to cause euglycemic diabetic ketoacidosis (eDKA), a diagnosis that may be challenging to establish in the emergency department (ED)., Case Report: This is a case report of missed eDKA in a 47-year-old male taking empagliflozin (a SGLT2 inhibitor) that presented to the ED with generalized weakness. His past medical history included multiple sclerosis (MS) diagnosed 4 years ago and type 2 diabetes mellitus. The patient attributed his weakness to MS. His neurologist was consulted and agreed with the plan to discharge the patient with diagnoses of asthenia and dehydration and a prescription of prednisone. The patient returned to the ED the next day with similar symptoms and was admitted to the hospital for treatment of eDKA. He was eventually treated per the hospital diabetic ketoacidosis (DKA) protocol and discharged home with instructions to discontinue empagliflozin. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: The increasing utilization of SGLT2 inhibitor in patients with type 2 diabetes mellitus will inevitably lead to more cases of eDKA seen in the ED. Emergency physicians need to consider this diagnosis in patients taking these medications that present with symptoms including weakness, nausea, vomiting, abdominal pain, and dehydration. Patients taking these medications should be warned about these symptoms, especially because they may be falsely reassured by relatively low plasma glucose levels on home glucometer readings., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Exposure to toxic industrial chemicals such as phosgene may occur through accidental or deliberate release. Inhalation may result in an acute lung injury which manifests as hypoxaemia with insufficient oxygen being delivered to the tissues resulting in hypoxia, respiratory failure and death. No effective pharmacological therapy currently exists and treatment remains supportive, often requiring intensive care facilities. In a mass casualty scenario the logistical burden of managing exposed individuals would rapidly overwhelm healthcare systems. This highlights the need to develop post exposure therapeutic strategies to minimise injury severity and increase survival in individuals exposed to toxic chemicals. Our research objective was to investigate a commercial off the shelf (COTS) therapy; ambient air continuous positive airway pressure (CPAP) support, initiated 1h post exposure to explore the concept that early intervention with positive airway pressure would reduce or ameliorate lung injury following exposure to phosgene. This study has demonstrated that CPAP, initiated before overt signs of exposure become manifest, significantly improved survival as well as improving some clinically relevant physiological measures of phosgene-induced acute lung injury over 24h., (Copyright © 2017 Crown Copyright. Published by Elsevier B.V. All rights reserved.)

Background: Commercially available crystalloid solutions used for volume replacement do not exactly match the balance of electrolytes found in plasma. Large volume administration may lead to electrolyte imbalance and potential harm. We hypothesised that haemodilution using solutions containing different anions would result in diverse biochemical effects, particularly on acid-base status, and different outcomes., Methods: Anaesthetised, fluid-resuscitated, male Wistar rats underwent isovolaemic haemodilution by removal of 10% blood volume every 15 min, followed by replacement with one of three crystalloid solutions based on acetate, lactate, or chloride. Fluids were administered in a protocolised manner to achieve euvolaemia based on echocardiography-derived left ventrical volumetric measures. Removed blood was sampled for plasma ions, acid-base status, haemoglobin, and glucose. This cycle was repeated at 15-min intervals until death. The primary endpoint was change in plasma bicarbonate within each fluid group. Secondary endpoints included time to death and cardiac function., Results: During haemodilution, chloride-treated rats showed significantly greater decreases in plasma bicarbonate and strong ion difference levels compared with acetate- and lactate-treated rats. Time to death, total volume of fluid administered: chloride group 56 (3) ml, lactate group 62 (3) ml, and acetate group 65 (3) ml; haemodynamic and tissue oxygenation changes were, however, similar between groups., Conclusions: With progressive haemodilution, resuscitation with a chloride-based solution induced more acidosis compared with lactate- and acetate-based solutions, but outcomes were similar. No short-term impact was seen from hyperchloraemia in this model., (Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objective: To evaluate the effects of a 6% hydroxyethyl starch (130/0.42) in either a buffered, electrolyte-balanced (HES-BAL) or saline (HES-SAL) carrier solution on electrolyte concentrations and acid-base parameters in healthy anaesthetized dogs., Study Design: Prospective randomised clinical study., Animals: A group of 40 client-owned dogs undergoing general anaesthesia for elective surgical procedures or diagnostic imaging., Methods: During anaesthesia, dogs were intravenously administered 15 mL kg -1 of either HES-SAL (n = 20) or HES-BAL (n = 20) over 30-40 minutes. Jugular blood samples were analysed before (T 0 ) and 5 minutes (T 5 ), 1 hour (T 60 ) and 3 hours (T 180 ) after fluid administration. Sodium, potassium, chloride, ionised calcium, phosphate, albumin, pH, venous pCO 2 , base excess (BE), bicarbonate and anion gap were determined and strong ion difference (SID) and total quantity of weak nonvolatile acids were calculated for each time point., Results: Chloride was significantly increased at T 5 , T 60 and T 180 compared with T 0 after HES-SAL, and was significantly greater after HES-SAL than after HES-BAL at T 5 (p = 0.042). Ionised calcium was significantly decreased at T 5 compared with T 0 after HES-SAL, and was significantly lower after HES-SAL than after HES-BAL at T 5 (p < 0.001). Bicarbonate was significantly lower after HES-SAL than after HES-BAL at T 5 (p = 0.004) and T 60 (p = 0.032). BE was significantly lower after HES-SAL than after HES-BAL at T 5 (p < 0.001) and T 60 (p = 0.007). SID was significantly decreased after HES-SAL at T 5 and T 60 compared with T 0 , and was significantly lower after HES-SAL than after HES-BAL at T 5 (p = 0.027). Mean electrolyte and acid-base parameters remained within or marginally outside of reference intervals., Conclusions and Clinical Relevance: Changes in both groups were minor and short-lived with either fluid in healthy individuals, but might become clinically relevant with higher fluid doses or in critically ill dogs., (Copyright © 2018 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.)

The effect of increasing levels of metals from anthropogenic sources on Antarctic invertebrates is poorly understood. Here we exposed limpets (Nacella concinna) to 0, 0.12 and 0.25 μg L− 1 lead for 12, 24, 48 and 168 h. We subsequently quantified the changes in protein abundance from gill, using 2D gel electrophoresis and mass spectrometry. We identified several antioxidant proteins, including the metal binding Mn-superoxide dismutase and ferritin, increasing abundances early on. Chaperones involved in the redox-dependent maturation of proteins in the endoplasmic reticulum (ER) showed higher abundance with lead at 48 h. Lead also increased the abundance of Zn-binding carbonic anhydrase at 12 h, suggesting a challenge to acid-base balance. Metabolic proteins increased abundance at 168 h, suggesting a greater ATP demand during prolonged exposure. Changes in abundance of the small G-protein cdc42, a signaling protein modifying cytoskeleton, increased early and subsequently reversed during prolonged exposure, possibly leading to the modification of thick filament structure and function. We hypothesize that the replacement of metals initially affected antioxidant proteins and increased the production of reactive oxygen species. This disrupted the redox-sensitive maturation of proteins in the ER and caused increased ATP demand later on, accompanied by changes in cytoskeleton., Significance: Proteomic analysis of gill tissue in Antarctic limpets exposed to different concentrations of lead (Pb) over a 168 h time period showed that proteomic changes vary with time. These changes included an increase in the demand of scavenging reactive oxygen species, acid-base balance and a challenge to protein homeostasis in the endoplasmic reticulum early on and subsequently an increase in energy metabolism, cellular signaling, and cytoskeletal modifications. Based on this time course, we hypothesize that the main mode of action of lead is a replacement of metal-cofactors of key enzymes involved in the scavenging of reactive oxygen species and the regulation of acid-base balance.

Study Objective: This study was designed to evaluate the therapeutic equivalence of balanced 6% hydroxyethyl starch (HES) 130/0.4 (Tetraspan) vs saline-based 6% HES 130/0.4 (Voluven) regarding the volume effect and the effect on acid-base status and renal functions in patients undergoing major urologic procedures., Design: Randomized comparative trial., Setting: Operating room and ward., Patients: Forty patients, American Society of Anesthesiologists statuses 1 and 2., Intervention: Patients were randomly allocated to receive either Voluven (n = 20) or Tetraspan (n = 20)., Measurements: Hemodynamic variables. Laboratory variables in the form of arterial blood gases, serum chloride and sodium levels, hemoglobin level, international normalized ratio, and kidney and liver functions were measured after induction of anesthesia (T1), at the end of surgery (T2), and on the first postoperative day (T3)., Main Results: Both groups were comparable regarding the total amount of study drugs and crystalloid consumption. No significant difference in hemoglobin levels between both groups, but there were significant differences between T1 and T2 hemoglobin within both groups and T3 hemoglobin in the Tetraspan group. Both groups were comparable regarding the renal functions, but there was a significant difference between T1 and T2 creatinine within both groups. No significant differences between both groups in liver functions and coagulation profile, but there were significant differences between values at T1, T2 and T3 within each group. Relative to baseline, both pH and bicarbonate decrease significantly in both groups. In the Voluven group, bicarbonate decreased significantly at the end of surgery relative to the Tetraspan group. Serum electrolytes did not vary between both groups., Conclusion: Both balanced 6% HES 130/0.4 (Tetraspan) and saline-based 6% HES 130/0.4 (Voluven) were equally effective for hemodynamic stabilization of patients undergoing major urologic procedures without any significant impact on acid-base status or renal functions., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Metabolic acidosis is a common complication of chronic kidney disease; it is typically caused by the accumulation of sulfate, phosphorus, and organic anions. Metabolic acidosis is correlated with several adverse outcomes, such as morbidity, hospitalization, and mortality. Thus, correction of metabolic acidosis is fundamental for the adequate management of many systemic complications of chronic kidney disease. In patients undergoing hemodialysis, acid-base homeostasis depends on many factors including the following: net acid production, amount of alkali given by the dialysate bath, duration of the interdialytic period, and residual diuresis, if any. Recent literature data suggest that the development of metabolic alkalosis after dialysis may contribute to adverse clinical outcomes. Our review is focused on the potential effects of different dialysate bicarbonate concentrations on hard outcomes such as mortality. Unfortunately, no randomized studies exist about this issue. Acid-base equilibrium is a complex and vital system whose regulation is impaired in chronic kidney disease. We await further studies to assess the extent to which acid-base status is a major determinant of overall survival in patients undergoing hemodialysis. For the present, the clinician should understand that target values for predialysis serum bicarbonate concentration have been established primarily based on observational studies and expert opinion. Based on this, we should keep the predialysis serum bicarbonate level at least at 22 mmol/l. Furthermore, a specific focus should be addressed by the attending nephrologist to the clinical and nutritional status of the major outliers on both the acid and alkaline sides of the curve., (Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Introduction: A previous meta-analysis reported lower umbilical artery pH with spinal anesthesia for cesarean delivery compared to general or epidural anesthesia. Ephedrine was used in the majority of studies. The objective of this study was to evaluate the effect of anesthetic technique on neonatal acid-base status now that phenylephrine has replaced ephedrine in our institution., Methods: We retrospectively reviewed our database to identify patients who underwent cesarean delivery and had umbilical artery pH available. We decided a priori to test separately cases where cesarean delivery was performed emergently (category I and II) or non-emergently (category III and IV). Multivariable models were constructed to detect significant predictors of lower umbilical artery pH., Results: One thousand sixty-four cases were included (647 emergent, 417 non emergent). In emergent cesarean delivery, anesthesia type was a significant predictor of lower umbilical artery pH (P <0.0001) with the pairwise comparisons showing lower neonatal umbilical artery pH [mean (95% CI)] with general anesthesia [7.16 (7.13, 7.19)] compared with spinal anesthesia [7.24 (7.22, 7.25)] and epidural anesthesia [7.23 (7.21, 7.24)], with no difference between spinal and epidural anesthesia. When excluding cases where general anesthesia was chosen due to insufficient time to place a neuraxial block or dose an existing epidural catheter, anesthesia type was not a predictor of lower umbilical artery pH. Anesthetic technique was not a predictor of lower umbilical artery pH in non-emergent cases., Conclusions: Spinal anesthesia was not associated with lower umbilical artery pH compared to other types of anesthesia. This might be due to the use of phenylephrine in our practice., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Alkali therapy of metabolic acidosis in patients with chronic kidney disease (CKD) with plasma total CO2 (TCO2) below 22 mmol/l per KDOQI guidelines appears to preserve estimated glomerular filtration rate (eGFR). Since angiotensin II mediates GFR decline in partial nephrectomy models of CKD and even mild metabolic acidosis increases kidney angiotensin II in animals, alkali treatment of CKD-related metabolic acidosis in patients with plasma TCO2 over 22 mmol/l might preserve GFR through reduced kidney angiotensin II. To test this, we randomized 108 patients with stage 3 CKD and plasma TCO2 22-24 mmol/l to Usual Care or interventions designed to reduce dietary acid by 50% using sodium bicarbonate or base-producing fruits and vegetables. All were treated to achieve a systolic blood pressure below 130 mm Hg with regimens including angiotensin converting enzyme inhibition and followed for 3 years. Plasma TCO2 decreased in Usual Care but increased with bicarbonate or fruits and vegetables. By contrast, urine excretion of angiotensinogen, an index of kidney angiotensin II, increased in Usual Care but decreased with bicarbonate or fruits and vegetables. Creatinine-calculated and cystatin C-calculated eGFR decreased in all groups, but loss was less at 3 years with bicarbonate or fruits and vegetables than Usual Care. Thus, dietary alkali treatment of metabolic acidosis in CKD that is less severe than that for which KDOQI recommends therapy reduces kidney angiotensin II activity and preserves eGFR.

Background: The infusion of crystalloid solutions is a fundamental part of the management of critically ill patients. These solutions are used to maintain the balance of water and essential electrolytes and replace losses when patients have limited gastrointestinal intake. They also act as carriers for intravenous infusion of medication and red cells. The most commonly used solution, 0.9% saline, has equal concentrations of Na(+) and Cl(-) even though the plasma concentration of Na(+) normally is 40 meq/L higher than that of Cl(-). The use of this fluid thus can produce a hyperchloremic acidosis in a dose-dependent manner, but it is not known whether this has clinical significance., Approach: The first part of this article deals with the significance of Na(+) and Cl(-) in normal physiology. This begins with examination of their roles in the regulation of osmolality, acid-base balance, and generation of electrochemical gradients and why the concentration of Cl(-) normally is considerably lower than that of Na(+). The next part deals with how their concentrations are regulated by the gastrointestinal tract and kidney. Based on the physiology, it would seem that solutions in which the concentration of Na(+) is "balanced" by a substance other than Cl(-) would be advantageous. The final part examines the evidence to support that point., Conclusions: There are strong observational data that support the notion that avoiding an elevated Cl(-) concentration or using fluids that reduce the rise in Cl(-) reduces renal dysfunction, infections, and possibly even mortality. However, observational studies only can indicate an association and cannot indicate causality. Unfortunately, randomized trials to date are far too limited to address this crucial issue. What is clear is that appropriate randomized trials will require very large populations. It also is not known whether the important variable is the concentration of Cl(-), the difference in concentrations of Na(+) and Cl(-), or the total body mass of Cl(-)., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: Several different crystalloid solutions are available for i.v. fluid administration but there is little information about their specific advantages and disadvantages., Methods: We performed a systematic search of MEDLINE, EMBASE, and CENTRAL up until May 17, 2012, selecting all prospective human studies that directly compared any near-isotonic crystalloids and reported any outcome., Results: From the 5060 articles retrieved in the search, only 28 met the selection criteria. There was considerable heterogeneity among the studies. Several articles reported an increased incidence of hyperchloraemic acidosis with the use of normal saline, and others an increase in blood lactate levels when large amounts of Ringer's lactate solutions were infused. From the limited data available, normal saline administration appears to be associated with increased blood loss and greater red blood cell transfusion volumes in high-risk populations compared to Ringer's lactate. Possible effects of the different solutions on renal function, inflammatory response, temperature, hepatic function, glucose metabolism, and splanchnic perfusion are also reported. The haemodynamic profiles of all the solutions were similar., Conclusions: Different solutions have different effects on acid-base status, electrolyte levels, coagulation, renal, and hepatic function. Whether these differences have clinical consequences remains unclear., (© The Author [2014]. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Objective: To compare acid-base balance and incidence of hyperchloraemic metabolic acidosis following administration of three crystalloid solutions to dogs undergoing anaesthesia for orthopaedic surgery., Study Design: Prospective, randomised, clinical study., Animals: Sixty dogs., Methods: During a non-standardised anaesthetic, 0.9% saline (S), Hartmann's solution (H) or a polyionic glucose-free maintenance solution (M) was administered IV at 10 mL kg(-1)  hour(-1) . Venous blood pH, PCO2 , PCV, total protein, urea, sodium, potassium and chloride concentrations were measured at induction of anaesthesia (T0) and after 2 hours of fluid therapy (T2). Base excess (BE), bicarbonate, corrected chloride concentration (corrCl), osmolality, change in plasma volume (PV) and strong ion gap (SIG) were calculated. Changes in variables within groups (1-sample Student's t-test/Wilcoxon signed rank test) and between groups (1-way anova/Kruskal-Wallis) were assessed. Data are presented as median (interquartile range). Significance was set at p < 0.05., Results: No significant differences existed between groups for pH, PCO2 , PCV, total protein, urea, potassium, corrCl, PV and SIG. Potassium significantly increased in all groups. Significant differences existed between groups S and M for BE, sodium, chloride, bicarbonate and osmolality, and between groups H and M for sodium and osmolality. Chloride concentration significantly changed from 116 (114-117) to 117 (116-119) mmol L(-1) in group S, 116 (115-118) to 115 (113-117) mmol L(-1) in group H and 116 (115-118) to 114 (113-118)  mmol L(-1) in group M. In groups H and M, sodium and osmolality decreased, and BE and bicarbonate concentration increased significantly. Plasma volume increased by 28 (14-44)%, 25 (5-40)% and 24 (13-33)% in groups S, H and M, respectively., Conclusion and Clinical Relevance: Hyperchloraemic metabolic acidosis did not develop after intraoperative 0.9% saline, Hartmann's solution or maintenance solution at 10 mL kg(-1)  hour(-1) for 2 hours in dogs undergoing elective orthopaedic surgery. Bicarbonate and BE increased after Hartmann's and maintenance solutions. Increases in potassium concentration were unexplained., (© 2013 The Authors. Veterinary Anaesthesia and Analgesia © 2013 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.)

Objective: To evaluate the cardiovascular, respiratory, electrolyte and acid-base effects of a continuous infusion of dexmedetomidine during propofol-isoflurane anesthesia following premedication with dexmedetomidine., Study Design: Prospective experimental study., Animals: Five adult male Walker Hound dogs 1-2 years of age averaging 25.4 ± 3.6 kg., Methods: Dogs were sedated with dexmedetomidine 10 μg kg(-1) IM, 78 ± 2.3 minutes (mean ± SD) before general anesthesia. Anesthesia was induced with propofol (2.5 ± 0.5 mg kg(-1) ) IV and maintained with 1.5% isoflurane. Thirty minutes later dexmedetomidine 0.5 μg kg(-1) IV was administered over 5 minutes followed by an infusion of 0.5 μg kg(-1)  hour(-1) . Cardiac output (CO), heart rate (HR), ECG, direct blood pressure, body temperature, respiratory parameters, acid-base and arterial blood gases and electrolytes were measured 30 and 60 minutes after the infusion started. Data were analyzed via multiple linear regression modeling of individual variables over time, compared to anesthetized baseline values. Data are presented as mean ± SD., Results: No statistical difference from baseline for any parameter was measured at any time point. Baseline CO, HR and mean arterial blood pressure (MAP) before infusion were 3.11 ± 0.9 L minute(-1) , 78 ± 18 beats minute(-1) and 96 ± 10 mmHg, respectively. During infusion CO, HR and MAP were 3.20 ± 0.83 L minute(-1) , 78 ± 14 beats minute(-1) and 89 ± 16 mmHg, respectively. No differences were found in respiratory rates, PaO2 , PaCO2 , pH, base excess, bicarbonate, sodium, potassium, chloride, calcium or lactate measurements before or during infusion., Conclusions and Clinical Relevance: Dexmedetomidine infusion using a loading dose of 0.5 μg kg(-1) IV followed by a constant rate infusion of 0.5 μg kg(-1)  hour(-1) does not cause any significant changes beyond those associated with an IM premedication dose of 10 μg kg(-1) , in propofol-isoflurane anesthetized dogs. IM dexmedetomidine given 108 ± 2 minutes before onset of infusion showed typical significant effects on cardiovascular parameters., (© 2013 The Authors. Veterinary Anaesthesia and Analgesia © 2013 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.)

The proximal tubule uses a complex process of apical acid secretion and basolateral bicarbonate absorption to regulate both luminal acidification and fluid absorption. One of the primary regulators of apical acid secretion is the luminal sodium-hydrogen exchanger expressed along the apical membrane of the proximal tubule. Similarly, the calcium-sensing receptor (CaSR) is also located along the luminal membrane of the proximal tubule. Here we investigated the role of CaSR in proton secretion and fluid reabsorption in proximal tubules by modulating luminal calcium concentration, using both in vivo micropuncture in rats and in vitro perfused mouse proximal tubules. Using CaSR knockout mice and a calcimimetic agent, we found that increased proton secretion and fluid reabsorption were CaSR dependent. Activating CaSR by either raising the luminal calcium ion concentration or by the calcimimetic caused a concomitant increase in sodium-dependent proton extrusion and fluid reabsorption, whereas in proximal tubules isolated from CaSR knockout mice varying calcium ion concentration had no effect. Application of a calcimimetic in lower concentrations of calcium ion stimulated these processes in vitro and in vivo. Thus, in both rats and mice, increased luminal calcium concentration leads to enhanced fluid reabsorption in the proximal tubule, a process related to activation of CaSR.

Background: The arterial pressure target for optimal splanchnic function during cardiopulmonary bypass (CPB) is uncertain. Thus, we aimed to compare the effects of two different arterial pressure targets during CPB on trans-splanchnic oxygenation, acid-base regulation, and splanchnic interleukin-6 (IL-6) and interleukin-10 (IL-10) flux., Methods: Sixteen patients undergoing cardiac surgery with CPB in a university affiliated hospital were subjected to a prospective alternating treatment design interventional study. We measured arterial and hepatic vein blood gases, electrolytes, IL-6, and IL-10 while targeting a mean arterial pressure (MAP) of between 60 and 65 mm Hg for 30 min, a MAP of between 80 and 85 mm Hg for 30 min (using norepinephrine infusion), and finally 60-65 mm Hg MAP target for 30 min., Results: The MAP targets were achieved in all patients [65 (4), 84 (4), and 64 (3) mm Hg, respectively; P<0.001] with a greater dose of norepinephrine infusion during the higher MAP target (P<0.001). With longer time on CPB, hepatic vein O2 saturation decreased, while magnesium, lactate, glucose, IL-6, and IL-10 increased independent of MAP target. The decrease in hepatic vein saturation was greater as the temperature increased (re-warming). Overall, there was trans-splanchnic oxygen, chloride, lactate, and IL-6 removal during CPB (P<0.001) and carbon dioxide, bicarbonate, glucose, and IL-10 release (P<0.001). Such removal or release was not affected by the MAP target., Conclusions: Targeting of a higher MAP during CPB by means of norepinephrine infusion did not affect splanchnic oxygenation, splanchnic acid-base regulation, or splanchnic IL-6 or IL-10 fluxes. Australian and New Zealand Clinical Trial Registry ACTRN 12611001107910.

Anion gap metabolic acidosis (AGMA) is commonly encountered in medical practice. Acetaminophen-induced AGMA is, however, not widely recognized. We report 2 cases of high anion gap metabolic acidosis secondary to 5-oxoproline accumulation resulting from acetaminophen consumption: the first case caused by acute one-time ingestion of large quantities of acetaminophen and the second case caused by chronic repeated ingestion in a patient with chronic liver disease. Recognition of this entity facilitated timely diagnosis and effective treatment. Given acetaminophen is commonly used over the counter medication, increased recognition of this adverse effect is of important clinical significance.

The objective was to measure the effects of VC (a uterotonic drug with vasodilator effects) in eutocic and dystocic sows, on the acid-base balance and some vitality traits of piglets at birth. Farrowing was induced with prostaglandin F2α. Four groups of sows (20 sows/group) were monitored; Groups 1 and 2 were eutocic sows, whereas Groups 3 and 4 were dam-fetal dystocic sows. Groups 1 and 3 (control) were given saline, whereas Groups 2 and 4 were given VC im (1.66 mg/kg of body weight) after the first piglet was born. Piglets' physio-metabolic performance was monitored peripartum. Treatment with VC reduced (P<0.0001) the percentage of intrapartum stillbirths in sows either with eutocic (5.2 vs. 10.0%) and dystocic (7.6 vs. 16.7%) farrowings and increased (P<0.0001) the number of pigs born alive without any evidence of AFS (89.9 vs. 79.9%, eutocic and 81.6 vs. 65.2%, dystocic). In addition, for the group of pigs with no acute fetal suffering (AFS), VC treatment enhanced survival responses with a half point grater vitality score in Group 4; it also reduced the latency to first teat contact by 6 min (P<0.05) in both treated groups compared to controls; and it improved the condition of the pigs' umbilical cord, with more adhered (98 vs. 86% in eutocic and 88 vs. 80% in dystocic; P<0.05) and less ruptured cords. Moreover, VC reduced the severity of adverse physio-metabolic indicators and the acid-base balance of piglets with AFS at birth by lowering blood lactate (89.8 vs. 93.5 mmol/L in eutocic groups and 94.6 vs. 100.2 mmol/L in dystocic groups; P<0.05), PaCO2 and Ca2+, and by increasing blood pH, HCO3 and PaO2 levels (P<0.05)., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objective: To assess cardiopulmonary and analgesic effects after administration of ropivacaine into the caudal epidural space of cattle., Study Design: Prospective, single-dose trial., Animals: Eight healthy mixed breed cows aged 8 ± 5 years and weighing 507 ± 112 kg., Methods: Caudal epidural anesthesia was produced in cows with 0.75% ropivacaine (0.11 mg kg(-1)). Onset time, duration and cranial spread of analgesia were recorded. Heart rate (HR), respiratory rate (f(R)), rectal temperature (RT), and mean arterial blood pressure (MAP) were measured prior to epidural administration (T(0) ) and at 15, 30, 60, 120, 180 and 240 minutes after epidural administration (T(15), T(30), T(60) , T(120) , T(180) and T(240) ). Arterial blood acid-base balance (pH, standard bicarbonate and base excess), gas tension (PaO(2), PaCO(2), SaO(2)) and electrolytes (Na(+), K(+), iCa(2+),Cl(-)) were recorded at T(0), T(30), T(60), T(120), T(180) and T(240). Ataxia was evaluated at T(0), T(30), T(60), T(120), T(180) and T(240) and at 1 hour intervals thereafter until analgesia was no longer present in each animal., Results: Epidurally administered ropivacaine induced variable analgesia extending bilaterally from the coccyx to S3. Time to onset of analgesia and mean duration in the perineal area were 15 ± 4 and 359 ± 90 minutes, respectively. Respiratory rate and RT increased from T(120) to T(240) when compared to the value at T(0) . Ionized calcium and chloride concentrations increased at T(180) and T(240) when compared to T(0). The other variables were not significantly different from baseline values (p > 0.05). Four animals were mildly ataxic., Conclusion and Clinical Relevance: Ropivacaine (0.75%, 0.11 mg kg(-1)) can be administered by caudal epidural injection to produce prolonged bilateral perineal analgesia with minimal ataxia and cardiopulmonary changes in standing cattle., (© 2012 The Authors. Veterinary Anaesthesia and Analgesia. © 2012 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesiologists.)

Objective: To report the severe metabolic acidosis identified in a group of 11 healthy mules anaesthetized with halothane for castration., Study Design: Data generated from a prospective study., Animals: Eleven mules aged 2.5-8 years, weighing 230-315 kg and 11 horses aged 1.5-3.5 years, weighing 315-480 kg., Methods: Animals were anaesthetized for castration as part of an electroencephalographic study. Preanaesthetic medication was acepromazine (0.03 mg kg(-1) ) administered through a preplaced jugular venous catheter. Anaesthesia was induced 30-90 minutes later with intravenous thiopental (10 mg kg(-1) ). After orotracheal intubation, anaesthesia was maintained with halothane vaporised in oxygen. The animals' lungs were ventilated to maintain the end-tidal CO(2) concentration between 3.9 and 4.5 kPa (29-34 mmHg). Anaesthetic monitoring included invasive blood pressure measurement via the auricular artery (mules) and submandibular branch of the facial artery (horses). Arterial blood gas samples were drawn from these catheters at three time points during surgery and pH, PaCO(2) , base excess (ecf) and were measured. Values were compared between groups using a Mann-Whitney test. p was taken as <0.05. Results are reported as median (range)., Results: PaCO(2) did not differ between groups but pH was significantly lower in mules [7.178 (7.00-7.29)] compared to horses [7.367 (7.24-7.43)] (p=0.0002). values were significantly lower in the mules [16.6 (13.0-22.3) mM] compared to horses [23.7 (20.9-23.7) mM] (p=0.0001), whilst base excess (ecf) was significantly more negative in the mules [-11.4 (-1.27 to -16) mM] compared to horses [-1.3 (-5.8 to +2.4) mM] (p=0.0004)., Conclusion and Clinical Relevance: This study demonstrated severe metabolic acidosis in healthy mules, which may have prompted intervention with drug therapies in a clinical arena. It is probable that the acidosis existed prior to anaesthesia and caused by diet, but other possible causes are considered., (© 2011 The Authors. Veterinary Anaesthesia and Analgesia. © 2011 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesiologists.)

A new Ru(II) complex of [Ru(bpy)2(Hmspip)]Cl2 {in which bpy=2,2'-bipyridine, Hmspip=2-(4-(methylsulfonyl)phenyl)-1H-imidazo[4,5-f][1,10]phenanthroline} have been synthesized and characterized. The ground- and excited-state acid-base properties of [Ru(bpy)2(Hmspip)]Cl2 and its parent complex of [Ru(bpy)2(Hpip)]Cl2 {Hpip=2-phenyl-1H-imidazo[4,5-f][1,10]phenanthroline} have been studied by UV-visible (UV-vis) and emission spectrophotometric pH titrations. [Ru(bpy)2(Hmspip)]Cl2 acts as a calf thymus DNA intercalators with a binding constant of 4.0×10(5) M(-1) in buffered 50 mM NaCl, as evidenced by UV-vis and luminescence titrations, steady-state emission quenching by [Fe(CN)6]4-, DNA competitive binding with ethidium bromide, reverse salt titrations and viscosity measurements., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Objective: Intravenous infusion of crystalloid solutions is a cornerstone of the treatment of hemorrhagic shock. However, crystalloid solutions can have variable metabolic acid-base effects, perpetuating or even aggravating shock-induced metabolic acidosis. The aim of this study was to compare, in a controlled volume-driven porcine model of hemorrhagic shock, the effects of three different crystalloid solutions on the hemodynamics and acid-base balance., Methods: Controlled hemorrhagic shock (40% of the total blood volume was removed) was induced in 18 animals, which were then treated with normal saline (0.9% NaCl), Lactated Ringer's Solution or Plasma-Lyte pH 7.4, in a blinded fashion (n = 6 for each group). Using a predefined protocol, the animals received three times the volume of blood removed., Results: The three different crystalloid infusions were equally capable of reversing the hemorrhage-induced low cardiac output and anuria. The Lactated Ringer's Solution and Plasma-Lyte pH 7.4 infusions resulted in an increased standard base excess and a decreased serum chloride level, whereas treatment with normal saline resulted in a decreased standard base excess and an increased serum chloride level. The Plasma-Lyte pH 7.4 infusions did not change the level of the unmeasured anions., Conclusion: Although the three tested crystalloid solutions were equally able to attenuate the hemodynamic and tissue perfusion disturbances, only the normal saline induced hyperchloremia and metabolic acidosis.

Rats with 5/6 nephrectomy have metabolic acidosis with a progressive decline in the glomerular filtration rate (GFR) ameliorated by endothelin and aldosterone antagonists and by dietary alkali. Interestingly, rats with 2/3 nephrectomy have no metabolic acidosis yet have a progressive GFR decline induced by acid retention and ameliorated by dietary alkali. Because patients without metabolic acidosis but with a moderately reduced GFR have a progressive GFR decline, ameliorated by oral sodium bicarbonate, we used rats with 2/3 nephrectomy to model these patients. Kidney acid content, endothelin-1, and aldosterone (measured by microdialysis) were higher in the rats with 2/3 nephrectomy than those with a sham operation despite no differences in plasma acid-base parameters. The GFR of the former but not the latter was lower at 25 than at 1 week after nephrectomy. Endothelin and aldosterone antagonism improved the preservation of GFR; however, this remained lower at week 24 than at week 1. By contrast, the GFR at weeks 24 and 1 was not different if the rats were given dietary alkali to normalize the kidney acid content. Antagonist of endothelin and aldosterone yielded no added GFR benefit. Thus, our study shows that (1) the decline in GFR in 2/3 nephrectomy is mediated by acid retention-induced kidney endothelin and aldosterone production; (2) receptor antagonism and dietary alkali are not additive; and (3) dietary alkali better preserves GFR than both endothelin and aldosterone receptor antagonism.

Objective: To assess the suitability of lingual venous blood (LBG) as an alternative to arterial blood (ABG) samples in determining acid-base balance and blood-gas status in dogs anesthetized for elective procedures and with medetomidine and isoflurane administration under experimental conditions., Study Design: Prospective, randomized clinical and experimental study., Animals: Clinical population of 18 ASA I/II dogs for elective surgery and five healthy Beagles (3 females and 2 males) for the experimental study., Methods: Blood sampling was simultaneously performed at dorsal pedal arterial and lingual venous sites, generating paired data. Two paired samples were collected from each dog in the clinical part and four from each dog in the experimental part (two during isoflurane anesthesia and two during isoflurane plus medetomidine). A modified Bland and Altman method was used to examine data from the clinical part and the experimental data were subjected to a paired sign's test following transformation where appropriate., Results: The pH of LBG overestimated ABG, with limits of agreement of (-0.01, 0.02). The partial pressure of carbon dioxide (PCO(2)) of LBG overestimated ABG by 0.6 mmHg [0.1 kPa], with limits of agreement of (-3.5, 4.6) mmHg [-0.5, 0.6 kPa]. The partial pressure of oxygen (PO(2)) of LBG underestimated ABG by 86.3 mmHg [-11.5 kPa], with limits of agreement of (-199.8, 27.3) mmHg [-26.6, 3.6 kPa]. During medetomidine administration values for PO(2) (p = 0.03) and lactate (p = 0.03) were lower for LBG when compared with ABG. The LBG value of PO(2) was lower (p = 0.03) during medetomidine and isoflurane administration versus isoflurane alone., Conclusions and Clinical Relevance: The pH and PCO(2) of LBG samples provide clinically acceptable substitutes of ABG samples in the dog population studied. The wider limits of agreement for PO(2) render it less reliable as a substitute for ABG. The difference in PO(2) identified between LBG and ABG during medetomidine administration may not preclude the use of LBG as substitutes for ABG samples.

Some athletes can have high intakes of l-glutamine because of their high energy and protein intakes and also because they consume protein supplements, protein hydrolysates, and free amino acids. Prolonged exercise and periods of heavy training are associated with a decrease in the plasma glutamine concentration and this has been suggested to be a potential cause of the exercise-induced immune impairment and increased susceptibility to infection in athletes. However, several recent glutamine feeding intervention studies indicate that although the plasma glutamine concentration can be kept constant during and after prolonged strenuous exercise, the glutamine supplementation does not prevent the postexercise changes in several aspects of immune function. Although glutamine is essential for lymphocyte proliferation, the plasma glutamine concentration does not fall sufficiently low after exercise to compromise the rate of proliferation. Acute intakes of glutamine of approximately 20-30 g seem to be without ill effect in healthy adult humans and no harm was reported in 1 study in which athletes consumed 28 g glutamine every day for 14 d. Doses of up to 0.65 g/kg body mass of glutamine (in solution or as a suspension) have been reported to be tolerated by patients and did not result in abnormal plasma ammonia levels. However, the suggested reasons for taking glutamine supplements (support for immune system, increased glycogen synthesis, anticatabolic effect) have received little support from well-controlled scientific studies in healthy, well-nourished humans.

Hyperosmolar increased-anion-gap metabolic acidosis without hyperglycemia has been reported after infusions of etomidate and other medications containing propylene glycol. We report a case of this biochemical abnormality with severe hyperglycemia. Cessation of the etomidate infusion along with other supportive measures resulted in prompt resolution of the metabolic acidosis and hyperglycemia.

High dietary protein intake generates endogenous acid production, which may adversely affect bone health. Alkaline potassium citrate (Kcit)(2) may contribute to the neutralization of the protein-induced metabolic acidosis. We investigated the impact of 2 levels of protein intake and Kcit supplementation on acid-base metabolism and bone status in rats. Two-month-old Wistar male rats were randomly assigned to 4 groups (n = 30 per group). Two groups received a normal-protein content (13%) (NP) or a high-protein (HP) content diet (26%) for 19 mo. The 2 other groups received identical diets supplemented with Kcit (3.60%) (NPKcit and HPKcit). Rats were pair-fed based on the ad libitum intake of the HP group. At 9, 16, and 21 mo of age, 10 rats of each group were killed. The HP diet induced a metabolic acidosis characterized by hypercalciuria, hypermagnesuria, and hypocitraturia at all ages. Kcit supplementation neutralized this effect, as evidenced by decreased urinary calcium and magnesium excretion by the HPKcit rats. Femoral bone mineral density, biomechanical properties, bone metabolism biomarkers (osteocalcin and deoxypyridinoline), and plasma insulin-like growth factor 1 levels were not affected by the different diets. Nevertheless, at 21 mo of age, calcium retention was reduced in the HP group. This study suggests that lifelong excess of dietary protein results in low-grade metabolic acidosis without affecting the skeleton, which may be protected by an adequate calcium supply.

Background: Terlipressin bolus infusion may reduce cardiac output and global oxygen supply. The present study was designed to determine whether dobutamine may counterbalance the terlipressin-induced depression in mixed-venous oxygen saturation (Svo) in patients with catecholamine-dependent septic shock., Methods: Prospective, randomized, controlled study performed in a university hospital intensive care unit. Septic shock patients requiring a continuous infusion of norepinephrine (0.9 microg kg(-1) min(-1)) to maintain mean arterial pressure (MAP) at 70 (sd 5) mm Hg were randomly allocated to be treated either with (i) sole norepinephrine infusion (control, n=20), (ii) a single dose of terlipressin 1 mg (n=19), or (iii) a single dose of terlipressin 1 mg followed by dobutamine infusion titrated to reverse the anticipated reduction in Svo2 (n=20). Systemic, pulmonary, and regional haemodynamic variables were obtained at baseline and after 2 and 4 h. Laboratory surrogate markers of organ (dys)function were tested at baseline and after 12 and 24 h., Results: Terlipressin (with and without dobutamine) infusion preserved MAP at 70 (5) mm Hg, while allowing to reduce norepinephrine requirements to 0.17 (0.2) and 0.2 (0.2) microg kg(-1) min(-1), respectively [vs1.4 (0.3) microg kg(-1) min(-1) in controls at 4 h; each P<0.001]. The terlipressin-linked decrease in Svo2 was reversed by dobutamine at a mean dose of 20 (8) microg kg(-1) min(-1) [Svo2 at 4 h: 59 (11)% vs 69 (12)%, P=0.028]., Conclusions: In human catecholamine-dependent septic shock, terlipressin (with and without concomitant dobutamine infusion) increases MAP and markedly reduces norepinephrine requirements. Although no adverse events were noticed in the present study, potential benefits of increasing Svo2 after terlipressin bolus infusion need to be weighted against the risk of cardiovascular complications resulting from high-dose dobutamine.

This study investigated the effect of high CO2 (4%) from embryonic day (ED)10 until ED16 on the acid-base balance and related parameters in the chicken embryo. From ED10 to ED16, blood was taken from a vein from the chorioallantois membrane and was analyzed for pH, partial pressure of CO2, partial pressure of O2 (pO2), [HCO3(-)], [K+], and [Ca2+]. Allantoic fluid was taken for measurement of pH, NH3-N, phosphate, and calcium concentration. The right tibia was ashed, and calcium was measured with atomic absorption spectroscopy. Embryos exposed to high CO2 showed a consistent higher blood pH than control embryos. Notwithstanding this alkalosis, bicarbonate concentration was significantly higher in the CO2 group from ED12 until ED16. Potassium concentration in the blood was significantly higher in the CO2 group from ED11 until ED16. The pH of the allantois was significantly higher on ED14 and ED15. Ammonia N concentration was significantly higher in the CO2-incubated embryos on ED12 and ED13, whereas phosphate did not differ between groups. Calcium per tibia dry weight did not differ between incubation conditions. We can conclude that embryos adapt to high CO2 during the second half of incubation by increasing blood HCO3(-). It appears that this increase in HCO3(-)is mainly the result of the stimulated intracellular exchange of H+ with K+, although temporary reabsorption of HCO3(-)by the kidney cannot be excluded.

A typical American diet contains amounts of sodium chloride far above evolutionary norms and potassium far below those norms. It also contains larger amounts of foods that are metabolized to noncarbonic acids than to organic bases. At baseline, in a steady state, diets that contain substantial sodium chloride and diets that are net acid producing each independently induce and sustain increased acidity of body fluid. With increasing age, the kidney's ability to excrete daily net acid loads declines, invoking homeostatically increased utilization of base stores (bone, skeletal muscle) on a daily basis to mitigate the otherwise increasing baseline metabolic acidosis, which results in increased calciuria and net losses of body calcium. Those effects of net acid production and its attendant increased body fluid acidity may contribute to development of osteoporosis and renal stones, loss of muscle mass, and age-related renal insufficiency. The inverted ratio of potassium to sodium in the diet compared with preagricultural diets affects cardiovascular function adversely and contributes to hypertension and stroke. The diet can return to its evolutionary norms of net base production inducing low-grade metabolic alkalosis and a high potassium-to-sodium ratio by 1) greatly reducing content of energy-dense nutrient-poor foods and potassium-poor acid-producing cereal grains, which would entail increasing consumption of potassium-rich net base-producing fruits and vegetables for maintenance of energy balance, and 2) greatly reducing sodium chloride consumption. Increasingly, evidence supports the health benefits of reestablishing evolutionary norms of dietary net base loads and high potassium and low sodium chloride loads. We focus here on the American diet's potential effects on bone through its superphysiologic content of sodium chloride.

Background: We tested the hypothesis that sodium nitroprusside (SNP) might improve the impairment of hepatosplanchnic microcirculatory blood flow (MBF) in septic shock., Methods: Fourteen pigs were anaesthetized and their lungs mechanically ventilated. Sepsis was induced with i.v. infusion of live Pseudomonas aeruginosa [1x10(8) colony forming units (CFU) ml(-1) kg(-1)] for 1 h. Sixty minutes later, the animals received in a random succession either SNP or normal saline for 30 min. Mean arterial pressure (MAP), cardiac index (CI), mean pulmonary artery pressure (MPAP), carbon dioxide tension of the ileal mucosa (PCO2; by gas tonometry), ileal mucosal and hepatic MBF by laser Doppler flowmetry, blood gases, and lactates were assessed before, during administration, and 30 min after discontinuing the test drug., Results: Bacterial infusion promoted hypodynamic shock (MAP -18%, CI -33%, ileal MBF -19%, and hepatic MBF -27%), which was converted to normodynamic shock by resuscitation. During SNP infusion, ileal mucosal MBF significantly increased (+19%) compared with control (P = 0.033). Although hepatic MBF increased (+42% from baseline), this did not differ from control. In order to maintain a constant central venous pressure and MAP, fluid loading and norepinephrine (P < 0.01) were increased. Acid-base status was not altered by SNP., Conclusions: In a resuscitated porcine model of the early phase of septic shock, SNP improved ileal mucosal MBF but required a concomitant increase in fluid and norepinephrine supplements to maintain constant systemic haemodynamic parameters.

The effect of Tris-Hydroxymethyl Aminomethane (THAM) on intracellular pH (pHi) is unknown. We previously demonstrated that the effect of sodium bicarbonate on pHi depends on the non-bicarbonate buffering system. First, human hepatocytes from hepatocytes cell culture (HepG2) were perfused with an acidotic artificial medium containing 5-mmol/L (H5) or 30-mmol/L (H30) concentrations of 4-(2-hydroxyethyl)-1-piperazineethane sulfonic acid (HEPES), a non-bicarbonate buffer. We studied the effect of THAM on the pHi in both conditions. We repeated the same protocol using an acidotic human blood with a 5% or 40% hematocrit. The pHi was measured with the pH-sensitive fluorescent dye bis-carboxyethyl carboxy-fluorescein (BCECF). Gas analysis was performed before and during the alkaline infusion. The results showed that THAM caused an intracellular alkalization that was higher when the non-bicarbonate buffer concentration was low (0.45 +/- 0.21 and 0.22 +/- 0.14 pH units with H5 and H30, respectively). A significant relationship was found between changes in pHi and changes in PCO(2). Similar results were obtained with the human blood. In conclusion, the intracellular alkalizing effect of THAM is caused by the induced decrease of PCO(2) linked to the extracellular non-bicarbonate buffer capacity: The smaller the concentration of extracellular non-bicarbonate buffer, the higher the PCO(2) decrease caused by THAM.

There is conflicting evidence regarding the effects of high protein intake on kidney health, especially as it relates to age. We investigated the short-term effects of a high-protein diet on kidney function and systemic acid-base homeostasis in older compared to younger adults. The subjects were healthy men and women either between the ages of 25 and 40 years (n=12) or 55 and 70 years (n=10). They underwent a two-period crossover trial with each period consisting of 2 weeks of usual diet followed by a 1-week experimental diet. During the experimental diet period subjects consumed metabolic meals that provided either low protein content (0.5 g protein/kg/day) or high protein content (2.0 g protein/kg/day). Outcome measures included blood and urine markers of renal function and acid-base balance. An analysis of variance was used to assess differences between age groups with respect to experimental diet. The older group, mainly women, showed an increase in glomerular filtration rate after the high-protein compared to low-protein diet; the younger group did not. Urinary pH was significantly lower, and ammonium excretion was significantly higher after the high-protein diet in both age groups, but neither group developed a clinically detectable acidosis after the week of receiving a high-protein diet.

We compared the acid-base balance in broiler chickens provided diets containing 2 dietary electrolyte balances (DEB), and administered with either adrenocorticotropic hormone (ACTH) or saline solution. Diets were moderate (174 mEq/kg) or high (241 mEq/kg) DEB formulated by altering Na-K-Cl based on actual analysis. The experiment was designed as a split plot, with the main unit consisting of 4 treatments and the factorial treatment structure arranged in a completely randomized design. Osmotic pumps delivered 8 IU of ACTH in saline/kg of BW per d for 7 d, or the same saline volume as used in ACTH at 1 microL/h for 7 d was implanted on d 35. Venous blood samples were collected on d 35 before the pumps were implanted and on d 42 and 49. Birds fed the high DEB diet exhibited significantly higher Na(+) and Ca(2+) levels than birds provided the moderate DEB diet on d 35. Infusion of ACTH significantly increased (P < or = 0.05) hematocrit, hemoglobin, partial pressure of CO(2) (pCO(2)), corticosterone, osmolality, and HCO(3)(-) and reduced pH, BW, partial pressure of O(2) (pO(2)), and plasma concentrations of Na(+) and Cl(-) in both diets compared with the control group on d 42. Similarly, the ACTH treatment significantly increased hematocrit, hemoglobin, Ca(2+), corticosterone, and osmolality and reduced (P < or = 0.05) pO(2), glucose, and BW on d 49. The diet formulated for high DEB partially lowered pCO(2) on d 42. Significant DEB x ACTH interactions were observed for pCO(2) and pO(2) on d 49. However, there was a reduction in pO(2) along with a concomitant increase in erythropoiesis under the ACTH treatment for both diets, compared with the saline control, because of the increased need for O(2) to support gluconeogenic energy production. This adaptive response provided greater numbers of erythrocytes and thus a higher amount of circulating hemoglobin to deliver O(2) for metabolism. The diet formulated for high DEB partially attenuated the adaptive stress condition in broiler chickens.

Background: We previously found rostral spread of spinal plain levobupivacaine to be less with prophylactic i.v. phenylephrine than with ephedrine during Caesarean delivery. This study investigated whether rostral spread of spinal hyperbaric bupivacaine is also less with phenylephrine than with ephedrine., Methods: The study was randomized and double blind. It compared phenylephrine 100 microg ml-1 (phenylephrine group, n=27), and ephedrine 4.5 mg ml-1 (ephedrine group, n=27), given by infusion during spinal anaesthesia for Caesarean delivery. Block height was assessed to cold and light touch sensation at 15, 30, 60, and 90-min after the spinal injection of 2.8 ml of hyperbaric 0.5% w/v bupivacaine, combined with 0.4 ml diamorphine (1 mg ml-1). Umbilical blood gas values were monitored during the study., Results: Block height was similar for both groups at all of the assessment times. Umbilical artery pH was higher with phenylephrine [median 7.32 (IQR 7.28-7.34)] than with ephedrine [7.20 (7.10-7.28)] (P<0.0001). There was a strong negative correlation between umbilical artery pH and spinal-delivery interval, but only with ephedrine: phenylephrine group, r2=0.09 (P=0.17), and ephedrine group, r2=0.53 (P<0.0001). Five-minute Apgar scores were higher with phenylephrine [10 (9-10)] than ephedrine [9 (9-9)] (P=0.009)., Conclusions: In contrast to its effect on spinal plain levobupivacaine, we did not find rostral spread of spinal hyperbaric bupivacaine to be less with prophylactic phenylephrine than with ephedrine. We observed an unexpectedly high incidence of fetal acidosis with ephedrine and found evidence that longer spinal-delivery intervals increase the risk of fetal acidosis developing with ephedrine, but not phenylephrine.

Objectives: To determine the minimum alveolar concentration (MAC) of isoflurane during the infusion of ketamine., Study Design: Prospective, experimental trial., Animals: Twelve adult spayed female cats weighing 5.1 +/- 0.9 kg., Methods: Six cats were anesthetized with isoflurane in oxygen, intubated and attached to a circle-breathing system with mechanical ventilation. Catheters were placed in a peripheral vein for the infusion of fluids and ketamine, and the jugular vein for blood sampling for the measurement of ketamine concentrations. An arterial catheter was placed to allow blood pressure measurement and sampling for the measurement of PaCO2, PaO2 and pH. PaCO2 was maintained between 29 and 41 mmHg (3.9-5.5 kPa) and body temperature was kept between 37.8 and 39.3 degrees C. Following instrumentation, the MAC of isoflurane was determined in triplicate using a tail clamp method. A loading dose (2 mg kg(-1) over 5 minutes) and an infusion (23 microg kg(-1) minute(-1)) of ketamine was started and MAC was redetermined starting 30 minutes later. Two further loading doses and infusions were used, 2 mg kg(-1) and 6 mg kg(-1) with 46 and 115 microg kg(-1) minute(-1), respectively and MAC was redetermined. Cardiopulmonary measurements were taken before application of the noxious stimulus. The second group of six cats was used for the measurement of steady state plasma ketamine concentrations at each of the three infusion rates used in the initial study and the appropriate MAC value determined from the first study., Results: The MAC decreased by 45 +/- 17%, 63 +/- 18%, and 75 +/- 17% at the infusion rates of 23, 46, and 115 microg kg(-1) minute(-1). These infusion rates corresponded to ketamine plasma concentrations of 1.75 +/- 0.21, 2.69 +/- 0.40, and 5.36 +/- 1.19 microg mL(-1). Arterial blood pressure and heart rate increased significantly with ketamine. Recovery was protracted., Conclusions and Clinical Relevance: The MAC of isoflurane was significantly decreased by an infusion of ketamine and this was accompanied by an increase in heart rate and blood pressure. Because of the prolonged recovery in our cats, further work needs to be performed before using this in patients.

Final urinary acidification is achieved by electrogenic vacuolar H(+)-ATPases expressed in acid-secretory intercalated cells (ICs) in the connecting tubule (CNT) and the cortical (CCD) and initial medullary collecting duct (MCD), respectively. Electrogenic Na(+) reabsorption via epithelial Na(+) channels (ENaCs) in the apical membrane of the segment-specific CNT and collecting duct cells may promote H(+)-ATPases-mediated proton secretion by creating a more lumen-negative voltage. The exact localization where this supposed functional interaction takes place is unknown. We used several mouse models performing renal clearance experiments and assessed the furosemide-induced urinary acidification. Increasing Na(+) delivery to the CNT and CCD by blocking Na(+) reabsorption in the thick ascending limb with furosemide enhanced urinary acidification and net acid excretion. This effect of furosemide was abolished with amiloride or benzamil blocking ENaC action. In mice deficient for the IC-specific B1 subunit of the vacuolar H(+)-ATPase, furosemide led to only a small urinary acidification. In contrast, in mice with a kidney-specific inactivation of the alpha subunit of ENaC in the CCD and MCD, but not in the CNT, furosemide alone and in combination with hydrochlorothiazide induced normal urinary acidification. These results suggest that the B1 vacuolar H(+)-ATPase subunit is necessary for the furosemide-induced acute urinary acidification. Loss of ENaC channels in the CCD and MCD does not affect this acidification. Thus, functional expression of ENaC channels in the CNT is sufficient for furosemide-stimulated urinary acidification and identifies the CNT as a major segment in electrogenic urinary acidification.

The cell membrane is an extremely complicated object. It participates in a large number of equilibria. For this reason, it is impossible to determine the parameters of all of them. It is the purpose of this work to define a limited number of averaged parameters in order to describe the equilibria between cell membrane components and environmental components. These parameters are the total acidic functional group concentration as well as the basic group concentration and their association constants with hydrogen or hydroxyl ions. The parameters were determined using the pH dependence of the electric surface charge density. The usefulness of these parameters was checked by studying the effect of green tea on liver cells in ethanol poisoning. Ethanol provokes an increase in concentration of functional groups, positively and negatively charged, as well as an increase in the basic groups association constant and a decrease in acidic groups association constant. Administering green tea partly compensates the changes provoked by ethanol poisoning. The parameters proposed in this work, C(TA), C(TB), K(AH) and K(BOH), are suited for monitoring the changes caused by various factors.

Rationale: Hyperchloremic acidosis is common in the critically ill and is often iatrogenic. We have previously shown that hyperchloremic acidosis increases nuclear factor-kappaB DNA binding in lipopolysaccharide-stimulated RAW 264.7 cells. However, evidence that hyperchloremic acidosis leads to increased inflammation in vivo has been limited to nitric oxide., Objectives: To determine if acidosis, induced by dilute hydrochloric acid (HCl) infusion, will increase circulating inflammatory mediator levels in an experimental model of severe sepsis in rats., Methods: Eighteen hours after inducing lethal sepsis by cecal ligation and puncture in 20 adult, male, Sprague-Dawley rats, we randomized animals into three groups. In groups 2 and 3, we began an IV infusion of 0.1 N HCl to reduce the standard base excess (SBE) by 5 to 10 mEq/L and 10 to 15 mEq/L, respectively. In group 1, we infused a similar volume of lactated Ringer solution. In all groups infusion continued 8 h or until the animal died., Measurements and Main Results: We measured arterial blood gases, whole-blood lactate, and chloride, tumor necrosis factor (TNF), interleukin (IL)-6, and IL-10 levels at 0 h, 4 h, and 8 h. All measured cytokines increased over time. Compared to group 1, animals in groups 2 and 3 exhibited greater increase in all three cytokines, with the greatest increases seen with severe acidosis., Conclusion: Moderate (SBE, - 5 to - 10) and severe (SBE, - 10 to - 15) acidosis, induced by HCl infusion, increases circulating levels of IL-6, IL-10, and TNF in normotensive septic rats.

The cardiorenal safety database from the Celecoxib Long-term Arthritis Safety Study (CLASS) was analyzed to examine whether supratherapeutic doses of celecoxib are associated with decreased renal function and blood pressure (BP) effects compared with standard doses of diclofenac and ibuprofen in osteoarthritis (OA) and rheumatoid arthritis (RA) patients.In total, 8059 patients were enrolled; 7968 received at least one dose of study drug (RA: N = 2183; OA: N = 5785). Patients received celecoxib, 400 mg twice a day (b.i.d.). (N = 3987); ibuprofen, 800 mg three times a day. (N = 1985); or diclofenac, 75 mg b.i.d. (N = 1996). Effects measured included: investigator-reported hypertension, edema or congestive heart failure, clinically important BP elevations, incidence of patients starting new antihypertensive medication, and increases in serum creatinine or reductions in creatinine clearance. Celecoxib was associated with a similar incidence of hypertension or edema to diclofenac but significantly lower than ibuprofen. The celecoxib group had significantly fewer initiations of antihypertensives versus ibuprofen. Systolic BP increases of >20 mmHg and above 140 mmHg occurred significantly less often with celecoxib compared with ibuprofen or diclofenac. Changes in serum creatinine or estimated creatinine clearance occurred in a similar percentage of patients taking celecoxib or ibuprofen; modest differences were evident against diclofenac. In patients with mild prerenal azotemia, significantly fewer patients taking celecoxib exhibited clinically important reductions in renal function (3.7%), compared with diclofenac (7.3%; P < 0.05) and ibuprofen (7.3%; P < 0.05). A supratherapeutic dose of celecoxib was associated with an improved cardiorenal safety profile compared with standard doses of either ibuprofen or diclofenac.

Water, compared with plasma at a pH of 7.4, is a weak acid. The addition of free water to a patient should have an acidifying effect (dilutional acidosis) and the removal of it, an alkalinizing effect (concentrational alkalosis). The specific effects of free water loss or gain in a relatively complex fluid such as plasma has, to the authors' knowledge, not been reported. This information would be useful in the interpretation of the effect of changes in free water in patients. Plasma samples from goats were either evaporated in a tonometer to 80% of baseline volume or hydrated by the addition of distilled water to 120% of baseline volume. The pH and partial pressure of carbon dioxide, sodium, potassium, ionized calcium, chloride, lactate, phosphorous, albumin, and total protein concentrations were measured. Actual base excess (ABE), standard bicarbonate, anion gap, strong ion difference, strong ion gap, unmeasured anions, and the effects of sodium, chloride, phosphate, and albumin changes on ABE were calculated. Most parameters changed 20% in proportion to the magnitude of dehydration or hydration. Bicarbonate concentration, however, increased only 11% in the evaporation trial and decreased only -2% in the dehydration trial. The evaporation trial was associated with a mild, but significant, metabolic alkalotic effect (ABE increased 3.2 mM/L), whereas the hydration trial was associated with a slight, insignificant metabolic acidotic effect (ABE decreased only 0.6 mM/L). The calculated free water ABE effect (change in sodium concentration) was offset by opposite changes in calculated chloride, lactate, phosphate, and albumin ABE effects.

Background: Recent studies support the use of alpha-agonists during regional anaesthesia in uncomplicated term pregnancies. We hypothesized that ephedrine and phenylephrine, administered for maternal hypotension following fetal hypoxaemia, are equal in respect of fetal outcome., Methods: At 117-132 days gestation, chronically instrumented, anaesthetized and mechanically ventilated ewes were randomized to receive boluses of ephedrine (n=9) or phenylephrine (n=8) for maternal epidural-induced hypotension after a period of fetal hypoxaemia. Uterine (QUtA) and placental (QUA) volume blood flows were measured with perivascular transit-time ultrasonic flow probes, and uterine (RUtA) and placental (RUA) vascular resistances were computed from volume blood flows and maternal and fetal mean arterial pressures. Uterine (PIUtA) and umbilical artery (PIUA) pulsatility indices were obtained by Doppler ultrasonography., Results: Ephedrine increased QUtA and decreased RUtA and PIUtA from a hypotensive to baseline level and had no significant effect on umbilical circulation. With phenylephrine, QUtA remained lower (P=0.011) and RUtA higher (P=0.043) than at baseline, although PIUtA decreased to baseline level. PIUA increased from baseline with phenylephrine (P=0.007), whereas QUA decreased (P=0.050). Maternal volume expansion with hydroxyethyl starch decreased RUtA significantly irrespective of the vasopressor used. There were no significant differences in fetal blood gas values or lactate concentrations between the ephedrine and phenylephrine groups., Conclusions: Despite the more favourable effects on uterine and placental circulations of ephedrine over phenylephrine, no significant differences in fetal acid-base status or lactate concentrations were observed.

Phosphodiesterase inhibitors, such as pentoxifylline and aminophylline, may reduce inflammatory cytokine-induced endothelial permeability. We tested the hypothesis that aminophylline treatment may ameliorate the pulmonary and extrapulmonary effects of endotoxemia in a rat model. In anesthetized rats, a tracheotomy was performed along with catheterization of a femoral vein and artery. Anesthesia, fluid balance, and normothermia were maintained throughout the 6-h experiment. A stable hemodynamic and gas-exchange baseline was established at which time the rats were randomly divided into three groups. Group I received aminophylline (1mg/kg) over 30 min followed by 0.5mg/kg/h. Group II received a single dose of endotoxin (4 mg/kg) while Group III received both aminophylline and endotoxin as described for Groups I and II, respectively. Gas-exchange profiles, mean arterial blood pressure, and heart rate were determined every 2h. At hour 6, the rats were euthanized and lung, kidney, and heart tissue were removed for determination of water content. As our control group, we utilized data from our previously published study involving an identical surgical procedure with normal saline. Endotoxemia produced characteristic respiratory and hemodynamic signs of sepsis including hypotension, hyperventilation, tachycardia, and renal and pulmonary edema. Aminophylline treatment failed to prevent these endotoxemia-induced respiratory and hemodynamic manifestations of sepsis, but significantly improved the acid-base imbalance that developed during surgical procedures in saline-treated control rats. Further studies are warranted to determine potentially beneficial doses of aminophylline and resulting theophylline serum concentrations under such septic conditions.

Unlabelled: Sevelamer is a recent phosphate binder that is mineral-free, and represents a great advance in the treatment of hyperphosphatemia in patients with hypercalcemia and/or gastric intolerance to calcium-based phosphate binders. The communications about the experience with the use of sevelamer in patients non-yet in dialysis is scanty. The aim of our study is to investigate retrospectively the gastrointestinal tolerance of sevelamer, their efficacy as phosphate binder and other parameters in a group of 89 patients with chronic renal failure in predialysis. We have analysed the effects of sevelamer at baseline and after 1, 3 and 6 months on the following data and parameters: calcium, phosphate, intact PTH, venous bicarbonate, urea, creatinine, creatinine clearance, side-effects, number of patients that were discontinued, and co-treatment during the study period with phosphate-based binders, calcitriol, lipid-lowering drugs and sodium bicarbonate., Results: 19 patients (21.3%) refused to continue with sevelamer at the first month (16 patients had digestive intolerance and 3 several symptoms). Serum phosphate fell at 3 months (5 +/- 0.8 mg/dl basal vs 4.8 +/- 0.7 mg/dl, p = 0.02) and 6 months (5 +/- 0.8 mg/dl basal vs 4.7 +/- 0.9 mg/dl, p = 0.07). Serum calcium fell at 6 months (9.8 +/- 0.7 mg/dl basal vs 9.4 +/- 0.6 mg/dl, p = 0.03). Venous bicarbonate and iPTH were unchanged, but the quantity of sodium bicarbonate administered increased significantly. Blood cholesterol fell at 1 months (193 +/- 49 mg/dl basal vs 173 +/- 52 mg/dl, p = 0.001) and 3 months (205 +/- 49 mg/dl basal vs 170 +/- 49 mg/dl, p = 0.004), in spite of a significant reduction of the dose of statins., Conclusions: Sevelamer is an effective phosphate binder in predialysis patients and also reduces significantly the serum cholesterol, improving the blood lipid profile. The levels of venous bicarbonate remained unchanged, at expenses of an increment in the dose of sodium bicarbonate supplementation.

Background: High protein diets are believed to cause kidney stone formation and bone loss, but the mechanisms mediating these changes are unknown. The purpose of this study was to create an animal model of animal protein excess and to evaluate the response of kidney and bone to the dietary protein load., Methods: Rats (12 per group) were pair-fed with a high (48%) and low (12%) casein diets that were otherwise identical in their content of sodium, potassium, calcium, phosphorus, and magnesium., Results: Compared with the low casein group, the high casein group delivered a substantial acid load during 59 days of study, since it significantly decreased urinary pH, and increased urinary ammonium, titratable acidity, and net acid excretion. Animals on high casein diet also had higher urinary volumes. On the high casein diet, urinary calcium excretion was significantly higher and urinary citrate excretion and concentration was significantly lower. On the high casein diet, urinary saturation of calcium phosphate was higher. Serum calcitriol concentration did not significantly differ between the two groups. Histomorphometric analysis of femur procured after 59 days on the diet showed marked increase in bone resorption in the high casein group. Hypocitraturia was associated with increased activity of sodium-citrate cotransporter in renal cortical brush-border membranes (BBM) in the high casein group., Conclusion: Both the kidney and bone contribute to the pathogenesis of hypercalciuria during high casein diet in rats. Hypocitraturia is probably renal in origin. This rat model will be useful in elucidating the mechanisms by which high protein intake increases the risk of nephrolithiasis and bone loss in human beings.

Background: Abnormal gastric tonometric variables, a surrogate for splanchnic ischemia, occur in approximately 50% of patients at the end of routine cardiac operations and are associated with postoperative morbidity. We sought to determine whether gastric tonometric variables deteriorate after left ventricular assist device insertion and to explore the association between abnormal gastric tonometric variables and vasoconstrictor use., Methods: Nineteen patients who had insertion of a left ventricular assist device were enrolled in a prospective, observational study. Automated air tonometry was used to determine the difference between gastric and arterial partial pressure of carbon dioxide (CO2 gap) at five time points perioperatively., Results: Compared with baseline, systemic blood flow was significantly increased at the end of operation (1.9 +/- 0.6 versus 2.9 +/- 0.7 L x min(-1) x m(-2), p < 0.0001). Tonometric variables, which were normal at baseline, became abnormal in 90% of patients (baseline CO2 gap 4 +/- 2 mm Hg versus end of operation CO2 gap 24 +/- 15 mm Hg, p < 0.0001). Elevated CO2 gaps correlated with larger doses of norepinephrine (r = 0.69, p = 0.001) and vasopressin (r = 0.88, p < 0.0001). Abnormal gastric tonometric variables at the end of operation correlated with postoperative intensive care unit length of stay (r = 0.70, p = 0.0009) and multiple organ dysfunction score (r = 0.64, p = 0.0033)., Conclusions: Despite a significant increase in systemic blood flow after left ventricular assist device implantation, abnormal gastric tonometric variables developed and were associated with larger vasoconstrictor dose. These data provide evidence that gastric ischemia can develop independently of changes in systemic blood flow and support the potential role of vasoconstrictors as a cause of splanchnic ischemia.