Electrolytes disturbances in cancer patients.

PURPOSE OF REVIEW: Hypernatremia, hyperphosphatemia, hypocalcaemia, hyperkalaemia and hypermagnesemia are electrolytes disturbances that can arise in cancer patients in relation to unique causes that are related to the cancer itself or its treatment and can lead to delay or interruption of cancer therapy. This article summarizes these main causes, the proposed pathophysiology and the recommended management for these disturbances. RECENT FINDINGS: There have been many cancer drugs approved in the field of oncology over the past several years and a subset of these drugs have been associated with electrolytes disturbances. This includes, for example, immune checkpoint inhibitor related hyperkalemia, fibroblast growth factor 23 inhibitor associated hyperphosphatemia and epidermal growth factor receptor inhibitor associated hypomagnesemia and hypocalcaemia. SUMMARY: This article provides an updated review of certain electrolytes disturbance in cancer patients and allows clinicians to have a greater awareness and knowledge of these electrolyte abnormalities in efforts to early recognition and timely management.

Assessing Acid-Base Status in Circulatory Failure: Relationship Between Arterial and Peripheral Venous Blood Gas Measurements in Hypovolemic Shock.

BACKGROUND AND OBJECTIVES: In severe circulatory failure agreement between arterial and mixed venous or central venous values is poor; venous values are more reflective of tissue acid-base imbalance. No prior study has examined the relationship between peripheral venous blood gas (VBG) values and arterial blood gas (ABG) values in hemodynamic compromise. The objective of this study was to examine the correlation between hemodynamic parameters, specifically systolic blood pressure (SBP) and the arterial-peripheral venous (A-PV) difference for all commonly used acid-base parameters (pH, Pco 2, and bicarbonate). DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: Data were obtained prospectively from adult patients with trauma. When an ABG was obtained for clinical purposes, a VBG was drawn as soon as possible. Patients were excluded if the ABG and VBG were drawn >10 minutes apart. RESULTS: The correlations between A-PV pH, A-PV Pco 2, and A-PV bicarbonate and SBP were not statistically significant (P = .55, .17, and .09, respectively). Although patients with hypotension had a lower mean arterial and peripheral venous pH and bicarbonate compared to hemodynamically stable patients, mean A-PV differences for pH and Pco 2 were not statistically different (P = .24 and .16, respectively) between hypotensive and normotensive groups. CONCLUSIONS: In hypovolemic shock, the peripheral VBG does not demonstrate a higher CO2 concentration and lower pH compared to arterial blood. Therefore, the peripheral VBG is not a surrogate for the tissue acid-base status in hypovolemic shock, likely due to peripheral vasoconstriction and central shunting of blood to essential organs. This contrasts with the selective venous respiratory acidosis previously demonstrated in central venous and mixed venous measurements in circulatory failure, which is more reflective of acid-base imbalance at the tissue level than arterial blood. Further work needs to be done to better define the relationship between ABG and both central and peripheral VBG values in various types of shock.

Combined effects of lung function, blood gases and kidney function on the exacerbation risk in stable COPD: Results from the COSYCONET cohort.

RATIONALE: Alterations of acid-base metabolism are an important outcome predictor in acute exacerbations of COPD, whereas sufficient metabolic compensation and adequate renal function are associated with decreased mortality. In stable COPD there is, however, only limited information on the combined role of acid-base balance, blood gases, renal and respiratory function on exacerbation risk grading. METHODS: We used baseline data of the COPD cohort COSYCONET, applying linear and logistic regression analyses, the results of which were implemented into a comprehensive structural equation model. As most informative parameters it comprised the estimated glomerular filtration rate (eGFR), lung function defined via forced expiratory volume in 1 s (FEV1), intrathoracic gas volume (ITGV) and (diffusing capacity for carbon monoxide (DLCO), moreover arterial oxygen content (CaO2), partial pressure of oxygen (PaCO2), base exess (BE) and exacerbation risk according to GOLD criteria. All measures were adjusted for age, gender, body-mass index, the current smoking status and pack years. RESULTS: 1506 patients with stable COPD (GOLD grade 1-4; mean age 64.5 ±â€¯8.1 y; mean FEV1 54 ±â€¯18 %predicted, mean eGFR 82.3 ±â€¯16.9 mL/min/1.73 m2) were included. BE was linked to eGFR, lung function and PaCO2 and played a role as indirect predictor of exacerbation risk via these measures; moreover, eGFR was directly linked to exacerbation risk. These associations remained significant after taking into account medication (diuretics, oral and inhaled corticosteroids), whereby corticosteroids had effects on exacerbation risk and lung function, diuretics on eGFR, BE and lung function. CONCLUSION: Even in stable COPD acid-base metabolism plays a key integrative role in COPD risk assessment despite rather small deviations from normality. It partially mediates the effects of impairments in kidney function, which are also directly linked to exacerbation risk.

Hyperchloremia and postoperative acute kidney injury: a retrospective analysis of data from the surgical intensive care unit.

BACKGROUND: Whether perioperative hyperchloremia can induce postoperative acute kidney injury (AKI) is controversial. We investigated the association between perioperative hyperchloremia and postoperative AKI in patients admitted to the intensive care unit (ICU) after surgery. METHODS: We performed a retrospective observational study of patients admitted to the surgical ICU at a single tertiary care hospital between January 2011 and June 2016. Our primary objective was to determine whether hyperchloremia or an increase in serum chloride levels was associated with postoperative AKI. Perioperative hyperchloremia was defined as serum chloride levels ≥ 110 mmol·L- 1 during postoperative days (PODs) 0-3. The increase in serum chloride levels was defined as the difference between preoperative and maximum postoperative serum chloride levels during the first 3 days after surgery. RESULTS: Of the 7991 patients included in the final analysis, 1876 (23.5%) developed hyperchloremia during PODs 0-3, and 1187 (14.9%) developed postoperative AKI. Exposure to hyperchloremia during the first 3 days after surgery was not associated with postoperative AKI (odds ratio, 1.09; 95% confidence interval, 0.80-1.49; P = 0.571). However, among patients with preoperative chronic kidney disease stage ≥ 3 (estimated glomerular filtration rate < 60 mL·min- 1·1.73·m- 2), the incidence of postoperative AKI was higher in patients with an increase > 6 mmol·L- 1 in serum chloride levels than in patients with an increase ≤ 1 mmol·L- 1 (odds ratio, 1.42; 95% confidence interval, 1.09-1.84; P = 0.009). In addition, the incidence of postoperative AKI stage ≥ 2 was not associated with exposure to hyperchloremia or with the increase in serum chloride levels during PODs 0-3, regardless of preoperative kidney function. CONCLUSIONS: Exposure to perioperative hyperchloremia is not associated with postoperative AKI in surgical ICU patients. However, in patients with moderate-to-severe chronic kidney disease (stage ≥ 3), a substantial perioperative increase in serum chloride levels may reflect a higher risk of AKI.

Dietary Acid-Base Load and Risk of Chronic Kidney Disease in Adults: Tehran Lipid and Glucose Study.

INTRODUCTION: The objective was to examine whether dietary acid load was associated with chronic kidney disease (CKD) in adults. MATERIALS AND METHODS: The cross-sectional analyses included 4564 participants, aged 20 years and older, who participated in the 4th phase of the Tehran Lipid and Glucose Study and had complete dietary and serum creatinine data. Dietary data were obtained from using a 147-item food-frequency questionnaire. Dietary acid load was calculated as the potential renal acid load (PRAL). Anthropometrics, blood pressure, and fasting plasma glucose, and lipids were measured. Chronic kidney disease was defined as an estimated glomerular filtration rate (GFR) less than 60 mL/min/1.73 m2 calculated using the Modification of Diet in Renal Disease equation. Risk of CKD was obtained in quartiles of PRAL with logistic recreation. RESULTS: The mean dietary PRAL of the participants was -22.0 mEq/d. After adjustment for age, sex, and body mass index, the odds ratio for CKD in the highest compared to the lowest quartile of PRAL was 1.38 (95% confidence interval [CI], 1.02 to 1.83). After additional adjustment for energy intake and smoking, the odds ratio for CKD in the 4th quartile of PRAL compared to the 1st was 1.42 (95% CI, 1.06 to 1.91). In the final model, after additional adjustment for dietary intake of total fat, carbohydrate, dietary fiber, fructose, sodium, diabetes mellitus, and hypertension, the risk of CKD in the highest dietary PRAL category, compared to the lowest, increased by 42%. CONCLUSIONS: After adjusting for possible confounding factors, we found that higher PRAL (more acidic diet) was associated with higher prevalent CKD in Iranian adults.

Does base deficit predict mortality in patients with severe traumatic brain injury?

OBJECTIVE: Base Deficit (BD) is a marker of tissue hypoxia in polytrauma patients. It guides resuscitative measures, and predicts outcomes, complications and mortality. The aim of this study was to examine the presence of BD in patients with isolated severe traumatic brain injury (TBI), and to assess if it correlates with the outcomes in these patients. METHOD: This was a retrospective observational study. All patients over the age of 16 years presenting to Aga Khan University Hospital from 2009 to 2013 with isolated TBI, were included. Data was extracted from 2009 to 2013. Glasgow Outcome Scale (GOS) of 4 and 5 at last follow up was categorized as favorable outcome. Data was analyzed using SPSS version 19 and receiver operative curve (ROC) was generated for BD as a predictor of mortality and unfavorable outcome. RESULTS: One hundred and eight patients were analyzed. Ninety-eight (90.7%) were males. Mean age was 36.69 ± 17.65. Eighty-eight (81.5%) patients had BD, while 20 (18.5%) patients had base excess. 62 (58.5%) of the patients had unfavorable outcomes. BD on admission had a statistically significant negative correlation with Glasgow Coma Scale (GCS) on presentation (r = -0.239, p = 0.025) and Revised Trauma Score (RTS) (r = -0.214, p = 0.046). However, there was no statistically significant difference in means of BD between survivors and non survivors. Area under receiver operator curve (ROC) for BD as a predictor of mortality statistically non-significant. CONCLUSION: Although BD is correlated with GCS at presentation and RTS, it is not a reliable prognostic marker for outcome and mortality in patients with isolated TBI.

Kidney involvement in leukemia and lymphoma.

Leukemia and lymphoma are hematologic malignancies that can affect any age group. Disease can be aggressive or indolent, often with multiorgan system involvement. Kidney involvement in leukemia and lymphoma can be quite extensive. Acute kidney injury (AKI) is quite prevalent in these patients, with prerenal and acute tubular necrosis being the most common etiologies. However other prerenal, intrinsic, and obstructive etiologies are possible. AKI can be a direct effect of the malignancy, a complication of the malignancy, or the consequence or side effect of chemotherapy. Nephrotic syndrome and glomerulonephritis, often presenting without overt kidney failure, have also been seen in all forms of leukemia and lymphoma. Lastly, the direct effects of the malignancy and complications from the tumor often result in numerous electrolyte disturbances and acid-base disorders, with life-threatening consequences if left untreated.

Established markers of renal and hepatic failure are not appropriate to predict mortality in the acute stage before extracorporeal life support implantation.

OBJECTIVES: End-organ function, especially of the kidney and liver, actual inflammation and acid-base balance affect the outcome in extracorporeal life support (ECLS) patients. However, the often unexpected necessity of ECLS implies that information on patients is scarce. Even established global scores are not always useful in the rapid decision process for ECLS. Therefore, we evaluated laboratory parameters for kidney or liver function and for inflammation and acid-base balance with regard to outcome. METHODS: The retrospective analysis includes 69 consecutive adult patients with veno-arterial ECLS. Laboratory markers for function of kidney (creatinine, urea) and liver (total bilirubin in plasma, glutamate oxaloacetate transaminase and glutamate pyruvate transaminase) as well as for inflammation (C-reactive protein, leucocyte counts) and acid-base balance (pH, lactate) were acquired within 24 h before ECLS implantation. RESULTS: A total of 38 patients (55%) could be weaned or bridged. Bridged patients were switched to ventricular assist devices, n=10, or total artificial hearts, n=2, and one patient underwent heart transplantation. Overall, 26 ECLS patients (38%) survived for >4 weeks. Thirty-one patients (45%) died on ECLS. About three out of four patients presented with impaired renal or hepatic performance, approximately two-thirds with signs of increased inflammatory state, and more than a half with deranged acid-base balance. Neither signs of hepatic or renal failure nor of inflammation or impaired acid-base balance allowed a prediction of survival in these patients. The outcome did also not depend on indication for ECLS implantation. However, there was a significant correlation between the patients' age and mortality (P=0.006). CONCLUSIONS: Our data indicate that renal and hepatic insufficiency, increased inflammatory state and deranged acid-base balance as determined by pre-operative laboratory data are not associated with poor outcome of ECLS. Further, survival is not related to indications for ECLS. In a number of patients, ECLS allows for successful bridging to other treatment options.

Does the model for end-stage liver disease score predict transfusion amount, acid-base imbalance, haemodynamic and oxidative abnormalities during living donor liver transplantation?

The model for end-stage liver disease (MELD) score is associated with the severity of liver failure in transplant patients. This study examined whether life-threatening stress factors during liver transplantation differed according to the patients' preoperative MELD scores. Forty-four patients who underwent living donor liver transplantation were divided into a high MELD group (MELD score ≥ 20) (n = 25) and a low MELD group (MELD score < 20) (n = 19). The volume of blood components transfused, acid-base homeostasis variables, and haemodynamic and oxidative variables were measured at each stage of the surgery. The systemic vascular resistance index was significantly lower in the high MELD group than in the low MELD group at all time points. The oxygen utility index and the oxygen extraction ratio were all significantly lower in the high MELD group than in the low MELD group only at the preanhepatic stage and not at later stages of surgery. Intraoperative transfusion volume and the severity of metabolic acidosis were not associated with the preoperative MELD score.

Administração de epinefrina e atropina na parada cardiorrespiratória em desequilíbrio ácido-básico: fundamentos para a prática: [revisão] / Administration of epinephrine and atropine in cardiopulmonary arrest in acid-base imbalance: foudations for practice: [review]

O atendimento a pacientes com parada cardiorrespiratória constitui-se em uma emergência clínica complexa que requer intervenções imediatas. O enfermeiro é responsável por grande parte desse atendimento, incluindo a administração medicamentosa. Desse modo, o objetivo deste estudo foi discutir a ação de catecolaminas na vigência de distúrbios metabólicos (acidose e alcalose) na PCR. Realizou-se uma revisão sistemática utilzando descritores relacionados ao tema, totalizando 138 artigos. As bases eletrônicas pesquisadas foram LILACS, MEDLINE e PAHO, entre janeiro de 1998 a dezembro de 2008. Esta revisão destacou uma série de estudos conclusivos sobre os fármacos utilizados na parada cardirrespiratória e apontou lacunas de conhecimento em relação ao objetivo proposto. Acredita-se que esses achados possam ser de grande valia para a qualidade desse atendimento, forneçam subsídios e apontem caminhos na direção de novas pesquisas.

Cloreto e status hidroeletrolítico e ácido-básico: importância clínica da determinação laboratorial / Chloride and hydroelectrolytic and acid base status: clinical importance of laboratorial determination

Apesar de o cloreto ser um exame amplamente disponível e solicitado em instituições de saúde, a maior pane dos médicos crê ser difícil interpretar seus resultados, estabelecer correlações com outros parâmetros laboratoriais associados e tomar decisões terapêuticas baseadas no mesmo. Devido à complexidade de sua homeostase e à intrincada correlação com o status hidroeletrolítico e ácido-básico, poucos médicos se sentem efetivamente aptos a aproveitar a valiosa informação clínica que ele pode revelar. Isto é agravado pela rarefeita bibliografia objetiva sobre o tema. Os autores desta revisão não foram capazes de encontrar nenhum capítulo especificamente dedicado ao cloreto nos principais livros-texto de Fisiologia, Clínica Médica e Nefrologia, disponíveis, à exceção de três revisões bibliográficas no Medline. Não obstante, tentamos organizar a informação tão claramente quanto possível, com o objetivo de tornar o cloreto uma ferramenta útil aos nossos colegas profissionais de saúde.

Even though chloride is a widely available and requested test in health institutions, most part of physicians find it difficult to interpret its results, establish correlations with other laboratory linked parameters and take therapeutic decisions based on it. Due to the complexity of its homeostatic balance and intrincated correlation to hydroelectrolytic and acid base status, few doctors feel actually able to fully profit from the valuable clinical information it can unfold. This is aggravated by the scarce objective bibliography on the issue. The authors of this review were not able to find any chapters specifically dedicated to chloride on major Physiology, Internal Medicine and Nephrology textbooks, but only three reviews on Medline. Nevertheless, we managed to organize the information as clearly as possible with the aim of making chloride test an useful tool to our fellow health professionals.

Hyperlactemia can predict the prognosis of liver resection.

Although hyperlactemia is known to accompany hepatic failure and metabolic acidosis, few reports examined the relationships between lactate concentrations and outcome after liver resection. We examined the ability of arterial plasma lactate concentration to predict the patient outcome after hepatectomy. The relationships of arterial lactate and base excess (BE) measured on admission to the intensive care unit (ICU) after hepatectomy to postoperative outcome were investigated in 151 consecutive patients. Lactate level was significantly higher in nonsurvivors than in survivors (P < 0.001), and in patients with postoperative complications than in those without complications (P < 0.001). Base excess was significantly reduced in nonsurvivors (P < 0.001) and in patients with postoperative complications (P = 0.004). The area under the receiver-operator curve of lactate to mortality was 0.86, whereas that of BE to the mortality was 0.82. Moderate correlation was observed between the lactate level at ICU admission and the highest total bilirubin concentration measured within 14 days after the surgery (r = 0.61), whereas the correlation between BE and bilirubin levels was lower (r = 0.35). Using multivariate analysis, the lactate level independently predicted mortality (P = 0.008) and morbidity (P = 0.013). Lactate (P < 0.001) and BE (P = 0.0068) levels both independently predicted the highest bilirubin concentration. The arterial plasma lactate concentration measured on admission to ICU seemed an excellent predictor of patient outcome after liver resection.

Experimental study on the role of endotoxin in the development of hepatopulmonary syndrome.

AIM: To evaluate the role of intestinal endotoxemia in the genesis of hepatopulmonary syndrome. METHODS: A rat model of cirrhosis was prepared with the method of compound factors. At the end of the eighth week, rats with cirrhosis were treated with 300 microg LPS/100 g body weight, and 1 g/rat of glycine about four h prior to LPS. After three h of LPS treatment, blood and tissues were collected for various measurements. Kupffer cells were isolated from male Wistar rats and cultured, and divided into five groups. Supernatant was harvested at 3 h after treatment with LPS for measurement of tumor necrosis factor-alpha (TNF-alpha). RESULTS: Our results showed that in rats with cirrhosis, slowed and deepened breath with occasional pause was. PaO2, PaCO2 and standard bicarbonate (SB) in arterial blood were decreased. Arterial O2 and actual bicarbonate (AB) were markedly decreased. There was a close correlation between decreased O2 and endotoxin. Metabolic acidosis accompanying respiratory alkalosis was the primary type of acid-base imbalance. The alveolar-arterial oxygen gradient was sharply widened. Massive accumulation of giant macrophages in the alveolar spaces and its wall and widened alveolar wall architecture were observed. The number of bacterial translocations in mesenteric lymph nodes increased. The ratio of TC99M-MAA brain-over-lung radioactivity rose. Endotoxin, and TNF-alpha, endothelin-1 (ET-1), nitric oxide (NO) in plasma and ET-1, carbon monoxide (CO) in lung homogenates increased. After administration of a given dosage of LPS in rats with cirrhosis, various pathological parameters worsened. Plasma level of endotoxin was related to TNF-alpha, ET-1, NO in plasma and ET-1, NO, CO in lung homogenates. TNF-alpha level was related to ET-1 and NO in plasma and lung homogenates and CO in lung homogenate as well. The level of TNF-alpha increased after infusion of LPS into culture supernatant of Kupffer cells in vitro. However, TNF-alpha significantly decreased after pretreatment with glycine, PD98059 and SB212850. Glycine could antagonize the effect of LPS in vivo and in vitro. CONCLUSION: Intestinal endotoxemia accompanying by cirrhosis may be an important mechanism in the development of hepatopulmonary syndrome in rats. Overproduction of TNF-alpha due to endotoxin stimulation of Kupffer cells via mitogen-activated protein kinase (MAPK) signal transduction pathway may be a major mechanism mediating the pathologic alterations of hepatopulmonary syndrome.

Are resuscitation and operation justified in injured patients with extreme base deficits (less than -20)?

BACKGROUND: This study assessed the outcome of injured patients in shock with an admission base deficit of -20 or less (approximate pH <7.0) at a level 1 trauma center. METHODS: A retrospective review was made of the trauma registry, supplemented by chart review, of all trauma patients admitted with a base deficit -20 or less from 1995 to 2002. Data collected included mechanism of injury, base deficit, Injury Severity Score(ISS), operative procedures, and outcome. Data are presented as mean +/- SD. RESULTS: Over the study period, 110 trauma patients (88% male; 31 +/- 13 years; 34% blunt trauma; ISS 26 +/- 15) were admitted with base deficit of -20 or less. Overall survival was 38%, with the majority of deaths occurring within hours of admission. CONCLUSIONS: An admission base deficit of -20 or less is associated with high mortality in patients with gunshot wounds (64%) or blunt trauma (70%). The majority of patients who die will do so within hours of admission. Beyond 24 hours, the survival rates of 73% for patients with blunt trauma, 79% for those with gunshot wounds, and 90% for those with stab wounds justify continuing resuscitation and reoperations.

Experimental animal models of muscle pain and analgesia.

Muscle pain is a prevalent clinical problem but can be difficult to treat because relatively little is known about nervous system mechanisms that mediate and modulate it. This review profiles four new animal models of muscle and deep tissue pain currently being used to elucidate mechanisms of muscle pain and analgesia.

Regulation of bone cell function by acid-base balance.

Bone growth and turnover results from the coordinated activities of two key cell types. Bone matrix is deposited and mineralised by osteoblasts and it is resorbed by osteoclasts, multinucleate cells that excavate pits on bone surfaces. It has been known since the early 20th century that systemic acidosis causes depletion of the skeleton, an effect assumed to result from physico-chemical dissolution of bone mineral. However, our own work has shown that resorption pit formation by cultured osteoclasts was absolutely dependent on extracellular acidification; these cells are inactive at pH levels above about 7.3 and show maximum stimulation at a pH of about 6.9. Bone resorption is most sensitive to changes in H+ concentration at a pH of about 7.1 (which may be close to the interstitial pH in bone). In this region pH shifts of < 0.05 units can cause a doubling or halving of pit formation. In whole-bone cultures, chronic HCO3- acidosis results in similar stimulations of osteoclast-mediated Ca2+ release, with a negligible physico-chemical component. In vivo, severe systemic acidosis (pH change of about -0.05 to -0.20) often results from renal disease; milder chronic acidosis (pH change of about -0.02 to -0.05) can be caused by excessive protein intake, acid feeding, prolonged exercise, ageing, airway diseases or the menopause. Acidosis can also occur locally as a result of inflammation, infection, wounds, tumours or diabetic ischaemia. Cell function, including that of osteoblasts, is normally impaired by acid; the unusual stimulatory effect of acid on osteoclasts may represent a primitive 'fail-safe' that evolved with terrestrial vertebrates to correct systemic acidosis by ensuring release of alkaline bone mineral when the lungs and kidneys are unable to remove sufficient H+ equivalent. The present results suggest that even subtle chronic acidosis could be sufficient to cause appreciable bone loss over time.

[Encrusted cystitis. Is it always alkaline?]. / Cistopatía incrustante. Siempre alcalina?

OBJECTIVE: To report on our series of encrusted cystopathy. METHODS: The clinical records of 37 patients (25 males, 67%; 12 females, 33%) with a histological diagnosis of encrusted cystopathy were reviewed. RESULTS: Only 11 patients (29.7%) met the classical criteria for alkaline encrusted cystitis. They had an initial or predisposing bladder lesion, irritative symptoms, passed calcareous material, a demonstrated or suspected urinary infection from ureolytic pathogens and alkaline urine. The remaining 26 patients (70.2%) with histologically demonstrated encrustations on the bladder wall did not meet the foregoing criteria. Fifty-seven percent of the patients had a previous history of bladder tumor resection and treatment with intravesical instillations. CONCLUSIONS: Alkaline encrusted cystopathy is an uncommon condition. Encrusting cystopathy can develop in the absence of ureolytic pathogens or alkaline urine. The bladder lesion on which the encrusting cystopathy is established, is determinant in the subsequent evolution.

Effect of locally applied drugs on the endolymphatic sac potential.

In Ménière's disease, an inner ear disorder related to an endolymphatic hydrops, an alteration of the functioning of the endolymphatic sac has been proposed. The endolymphatic sac is assumed to be involved in the secretion/resorption of endolymph. The epithelial transport systems have been indirectly studied by the recording of the endolymphatic sac transepithelial potential (ESP) in control conditions and after the local injection of drugs such as diuretics that have been proposed in the treatment of Ménière's disease. The ESP was recorded, in vivo, in guinea pigs up to 150 minutes after the perisaccular injection of 5 microL of a 150 mmol/L (mM) NaCl solution containing various drugs known to inhibit ionic transport systems. The initial ESP was +8.4+/-0.3 mV (mean +/- SEM, n = 78). The basolateral injection of 5 microL of 150 mM NaCl induced an ESP decrease of 64%+/-6.0% (n = 12), 5 minutes after the end of the injection. Then ESP increased, returning to its initial value at 60 minutes and surpassing it at 120 minutes. Diuretics such as acetazolamide (10[-3] mol/L [M]), an inhibitor of carbonic anhydrase, and amiloride (10[-4] M), an inhibitor of Na channel or Na/H exchanger, decreased the ESP recovery. At variance, bumetanide (10[-6] M, 10[-4] M), the Na-K-Cl cotransport inhibitor, and chlorothiazide (10[-4] M), a Na-Cl cotransporter inhibitor, failed to alter the ESP as compared with the control group. Ouabain (10[-3] M), the Na+,K+-adenosine triphosphatase (ATPase) inhibitor, prevented the ESP recovery otherwise observed 60 minutes after the NaCl injection. Bafilomycin A1, the inhibitor of the vacuolar-type H+-ATPase, prevented the recovery of the ESP with a log-dose/effect (10[-5] M, 10[-6] M, 10[-8] M). Disulfonic acid stilbene (DIDS) (10[-4] M), an inhibitor of transporters involving HCO3-, also prevented the ESP recovery. These results suggest that the genesis of the ESP was highly dependent on acid-base transport systems including carbonic anhydrase, a vacuolar-type H+-ATPase, and an anionic transport system blocked by DIDS. Further studies are needed to confirm the alteration of the acid-base balance in this epithelium and its possible involvement in the pathogenesis of Ménière's disease.

Arterial blood gas abnormalities in patients with dizziness.

Arterial blood gases were analyzed in 121 patients with dizziness. Sixty-one showed arterial blood gas abnormalities in the dizziness period. An increase in bicarbonate was seen in 57, increases in both bicarbonate and arterial carbon dioxide pressure in 8, and a low arterial oxygen pressure in 22 patients. The frequency of the abnormalities was significantly higher in those with central-peripheral diseases than in those with Meniere's disease. Arterial blood gases were also checked at random in the remission period in 22 patients. The frequency of dizziness recurrence was significantly higher in patients with the abnormalities in the remission period than in patients without them. These results indicate that approximately half of the patients with dizziness tend to have arterial blood gas abnormalities in the dizziness period. It is suggested that arterial blood gas abnormalities cause temporary vestibular dehabituation that increases the frequency of dizziness in central-peripheral diseases and Meniere's disease.