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PubMed1993

Effects of infused sodium acetate, sodium lactate, and sodium beta-hydroxybutyrate on energy expenditure and substrate oxidation rates in lean humans.

Infusion of sodium acetate in lean humans results in a decrease in respiratory exchange ratio, which may be advantageous in patients with respiratory failure. However, this potential decrease in respiratory work was observed to be offset by significant thermogenesis. The metabolic effects of sodium acetate, sodium lactate, and sodium beta-hydroxybutyrate, infused at a rate of 20 mumol.kg-1.min-1 for 3 h, was monitored in six healthy human volunteers. Respiratory exchange ratio decreased from 0.85 +/- 0.02 at baseline to 0.75 +/- 0.02, 0.75 +/- 0.02, and 0.80 +/- 0.02, after acetate, lactate, or beta-hydroxybutyrate, respectively (P < 0.05 for each). Acetate produced a larger thermic effect (22.7% of energy infused) than did lactate (16.3%) or beta-hydroxybutyrate (13.6%). Thus, sodium salts of organic acids may potentially decrease the respiratory requirements by decreasing the respiratory exchange ratio. However, this effect is partially offset by the thermic effect of these substrates. The maximal doses and safety of these anions during larger infusion periods remain to be determined.

3-Hydroxybutyric Acid↗
PubMed1991

Sodium deficient rats are unmotivated by sodium chloride solutions mixed with the sodium channel blocker amiloride.

Rats were made sodium deficient by furosemide injection and then offered 20 min of access to 0.05 M NaCl mixed with the sodium channel blocker amiloride. Compared with a sodium deficient control group that was also offered 0.05 M NaCl, these rats drank very little. A subsequent test conducted in the same manner with 20 min of access to 0.3 M NaCl mixed with amiloride produced similar results. It is concluded that amiloride blocks the neural information required for generating the attractive taste of NaCl to the sodium deficient rat.

Amiloride↗
PubMed2004

Sodium removal and sodium concentration during peritoneal dialysis: effects of three methods of sodium measurement.

BACKGROUND: Sodium removal (NaR) may have a major impact on the survival of peritoneal dialysis patients. The dialysate/plasma sodium concentration ratio (D/P(Na)) is an indirect index of transcellular water transport by aquaporin channels, and thus of ultrafiltration. Sodium concentration can be assessed by means of flame photometry (F), and direct (D-ISE) or indirect ion-selective electrodes (I-ISE), but these methods have different properties. I-ISE is being used increasingly in clinical laboratories. The aim of this study was to evaluate NaR and D/P(Na) using the three different measurement methods. METHODS: We performed peritoneal equilibration tests (PETs) in 44 peritoneal dialysis patients and calculated the NaR. We also calculated D/P(Na) during the test; plasma and dialysate sodium concentrations were measured by F, D-ISE and I-ISE. RESULTS: NaR was lower (P<0.001) with D-ISE (69+/-29 mmol) than with F (81+/-29 mmol) or I-ISE (79+/-28 mmol). D/P(Na) was also lower at baseline (0.92+/-0.02 vs 0.95+/-0.02 and 0.95+/-0.02; P<0.001), after 60 min (0.87+/-0.03 vs 0.90+/-0.03 and 0.90+/-0.03; P<0.001) and at the end of PET (0.88+/-0.04 vs 0.92+/-0.04 and 0.92+/-0.04; P<0.001) when measured by D-ISE in comparison with F and I-ISE, respectively. CONCLUSIONS: NaR and D/P(Na) were lower when measured by the D-ISE method compared with the F and I-ISE methods. NaR and D/P(Na) were similar when measured by F or I-ISE. I-ISE can be used reliably in the evaluation of NaR and D/P(Na) in everyday clinical practice of peritoneal dialysis.

Clinical Chemistry Tests↗
PubMed2004

Final report on the safety assessment of octoxynol-1, octoxynol-3, octoxynol-5, octoxynol-6, octoxynol-7, octoxynol-8, octoxynol-9, octoxynol-10, octoxynol-11, octoxynol-12, octoxynol-13, octoxynol-16, octoxynol-20, octoxynol-25, octoxynol-30, octoxynol-33, octoxynol-40, octoxynol-70, octoxynol-9 carboxylic acid, octoxynol-20 carboxylic acid, potassium octoxynol-12 phosphate, sodium octoxynol-2 ethane sulfonate, sodium octoxynol-2 sulfate, sodium octoxynol-6 sulfate, and sodium octoxynol-9 sulfate.

Octoxynols are ethoxylated alkylphenols in which the size of the molecule is related to the number of moles of ethylene oxide used in synthesis. Reactions are performed at elevated temperature, under pressure, and in the presence of NaOH. It is possible that the synthesis may leave trace amounts of ethylene oxide, 1,4-dioxane, and unreacted C9 phenols. Octoxynols of various chain lengths as well as octoxynol salts and organic acids function in cosmetics either as surfactants--emulsifying agents, surfactants--cleansing agents, surfactant--solubilizing agents, or surfactants--hydrotropes in a wide variety of cosmetic products at concentrations ranging from 0.0008% to 25%, with most less than 5.0%. The octoxynols are chemically similar to nonoxynols, the safety of which were previously considered. Long-chain nonoxynols (9 and above) were considered safe as used, whereas short-chain nonoxynols (8 and below) were considered safe as used in rinse-off products and safe at concentrations less than 5% in leave-on formulations. Acute exposure of hamsters to Octoxynol-9 by bronchopulmonary lavage produced pneumonia, pulmonary edema, and intra-alveolar hemorrhage. Octoxynol-9 at doses over 1 g/kg was toxic in rats and in mice in acute oral toxicity studies. No significant effects were noted in short-term oral studies of Octoxynol-9 in rats, in subchronic oral studies of Octoxynol-40 in rats and dogs, or in chronic oral studies of Octoxynol-40 in rats. The intraperitoneal LD50 of Octoxynol-9 in rats and mice was around 100 mg/kg. In skin irritation studies, octoxynols ranged from nonirritating to moderately irritating. Octoxynols were not ocular irritants in one rabbit study, but in others there was ocular irritation. No immune system toxicity in CF-1 female mice was noted following the intraperitoneal injection of Octoxynol-9 followed by subcutaneous immunization with sheep red blood cells (SRBCs). Octoxynol-9 produced no humoral and cell-mediated immune responses, or autoimmune response in mice. In the Ames test, Octoxynol-1 was not mutagenic with and without metabolic activation nor was Octoxynol-9 clastogenic. Results for Octoxynol-9 were negative in the following assays: unscheduled DNA synthesis, hypoxanthine guanine phosphoribosyl transferase mutation assay, malignant transformation assay, DNA alkaline unwinding test, and mouse lymphoma thymidine kinase locus forward mutation assay. Ethoxylated alkylphenols are generally considered to be estrogenic in that they mimic the effects of estradiol. Dermal exposure at three dose levels of rats to Octoxynol-9 failed to induce any malformations by category (external, visceral, or skeletal) or by individual anatomical location that were different from controls at statistically significant level. An increased incidence of a vestigial thoracic rib was observed in all dose groups. Octoxynol-9 also did not induce developmental toxicity (number of viable litters, liveborn per litter, percentage survival, birth weight per pup, and weight gain per pup) in female specific pathogen-free CD-1 mice dosed daily by gavage on gestation days 6 through 13. No reproductive toxicity was seen in male albino rats which received 5% Octoxynol-40 in the diet daily for 3 months; however, in an in vitro test, Octoxynol-9 (0.24 mg/ml) totally immobilized all human spermatozoa within 20 s. Women who used Nonoxynol-9 or Octoxynol-9 as spermicides, but who did become pregnant, did not have an increase in the overall risk of fetal malformations. In a human skin irritation study, formulations containing 2.0% Octoxynol-9 were classified as moderately irritating and minimally irritating, respectively, in a 24-h single-insult, occlusive patch test. Octoxynol-9 (1.0%) was classified as a nonirritant in a clinical study of nine subjects patch tested for 4 consecutive days. The skin sensitization potential of Octoxynols-1, -3, -5, -9, and -13 was evaluated using 50 subjects. Octoxynol-1 induced sensitization in two subjects; all other results were negative. No sensitization was observed in the following studies: 8.0% Octoxynol-9 in 103 subjects, 0.5% Octoxynol-9 in 102 subjects, and 0.1% Octoxynol-9 in 206 subjects. Concerns about even trace levels of 1,4-dioxane, ethylene oxide, or unreacted C9 led to the recommendation that levels be limited. Concerns about the ocular irritancy of short-chain octoxynols led to a recommendation that they should not be used in products that will be used in the area surrounding the eyes. A limitation on the use concentration for short-chain octoxynols (8 and below) arose from consideration of the skin sensitization potential of octoxynols and the recognition that the short-chain octoxynols could be absorbed into the skin more than the long-chain octoxynols. Overall, based on the available data, it was concluded that long-chain octoxynols (9 and above) are safe as used, whereas short-chain octoxynols (8 and below) are safe as used in rinse-off products and safe at concentrations less than 5% in leave-on formulations.

Animals↗
PubMed1985

Clinical evaluation of sodium bicarbonate, sodium L-lactate, and sodium acetate for the treatment of acidosis in diarrheic calves.

Thirty-six dehydrated diarrheic neonatal calves were used to study the effects of various alkalinizing compounds on acid-base status, the changes in central venous pressure (CVP) in response to rapid IV infusion of large volumes of fluid, and the correlation of acid-base (base deficit) status, using a depression scoring system with physical determinants related to cardiovascular and neurologic function. Calves were allotted randomly to 4 groups (9 calves/group). Over a 4-hour period, each calf was given two 3.6-L volumes (the first 3.6 L given in the first hour) of a polyionic fluid alone (control group) or were given the polyionic fluid with sodium bicarbonate, sodium L-lactate, or sodium acetate added (50 mmol/L). Acid-base status, hematologic examination, and biochemical evaluations were made immediately before infusion of each fluid (at entry) and after 3.6, 4.8, and 7.2 L of fluid had been given. Compared with control values, bicarbonate, lactate, and acetate had significantly greater alkalinizing effects on pH (P less than 0.01) and base deficit (P less than 0.01) after 3.6, 4.8, and 7.2 L of fluid were given. Bicarbonate had the most rapid alkalinizing effect and induced greater changes in base deficit (P less than 0.01) than did acetate or lactate at each of the 3 administered fluid volumes evaluated. Acetate and lactate had similar alkalinizing effects on blood. Rehydration alone did not improve acid-base status. The CVP was elevated in 10 (28%) of the 36 calves after 1 hour of fluid (3.6 L) administration, but significant differences in body weight, PCV, and clinical condition or depression score at entry were not found between calves with elevated CVP and those with normal CVP.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetates↗
PubMed1978

Solubilization of napthalene by sodium cholate and pattern of self-association of sodium cholate in 0.15 M sodium chloride.

Naphthalene solubility was determined in aqueous 0.15 M NaCl containing sodium cholate in the 0-0.05 M concentration range at 25 +/- 0.1 degrees. Sodium cholate tends to self-associate in aqueous solutions. Most often, the association pattern has been described in terms of a monomer-micellar model in which it is assumed that no association occurs below the critical micelle concentration. By comparison of the experimental solubilization curve with curves calculated on the basis of the monomer-micellar model, it was shown that this model is inappropriate for the self-association pattern of sodium cholate. The solubility data were consistent with a model that assumes that sodium cholate associates to form dimers, trimers, and higher aggregates with an average aggregation number of 7.63. Model calculations suggest that naphthalene is solubilized by dimers and higher aggregates. Solubilization of naphthalene by trimers appears to be negligible.

Cholic Acids↗
PubMed2006

In vitro cytotoxicity assessment of the biocidal agents sodium o-phenylphenol, sodium o-benzyl-p-chlorophenol, and sodium p-tertiary amylphenol using established fish cell lines.

The cytotoxicity of three biocidal agents frequently employed as active ingredients in phenolic-based disinfectants, were evaluated in three established fish cell lines (EPC, CHSE and RTG-2). Cell viability was assessed using two fluorescent indicator dyes, Alamar Blue for metabolism and neutral red for lysosomal activity. Total protein content was also quantified as a measure of cell detachment. In order to evaluate the sensitivity of the cell cultures, the results obtained were compared with toxicity data obtained from a previous study with the same three compounds and the in vivo lethality test with rainbow trout. Results from this study established that each of the three cell lines ranked the tested chemicals in the same order of toxicity as the in vivo test; however, the cell cultures were found to be an order of magnitude less sensitive than whole fish studies with the same compounds. The chemical sodium o-benzyl-p-chlorophenol was consistently ranked the most toxic of the tested compounds with each cell line and the endpoints employed. The rank order of toxicity was always sodium o-benzyl-p-chlorophenol > sodium p-tertiary amylphenol > sodium o-phenylphenol. The EPC cells were found to be the most sensitive cell line tested based on Alamar Blue IC(50) data, and the Alamar Blue assay was consistently found to be the most sensitive endpoint of the three cytotoxicity assays employed.

Animals↗
PubMed1986

Stability of clindamycin phosphate with aztreonam, ceftazidime sodium, ceftriaxone sodium, or piperacillin sodium in two intravenous solutions.

In admixtures containing clindamycin and either aztreonam, ceftazidime, ceftriaxone, or piperacillin in either 5% dextrose injection (D5W) or 0.9% sodium chloride injection (NS), the stability of each drug was studied. Each of the following combinations of drugs was added to 100-mL glass bottles of base solution: clindamycin phosphate 0.9 g and aztreonam 2.0 g, clindamycin phosphate 0.9 g and ceftazidime sodium 2.0 g, clindamycin phosphate 1.2 g and ceftriaxone sodium 2.0 g, and clindamycin phosphate 0.9 g and piperacillin sodium 4.0 g. Duplicate samples were prepared. Admixtures containing each single drug were also tested. Samples were visually inspected and tested for pH and drug concentration immediately after mixing and at 1, 4, 8, 12, 24, and 48 hours of storage in room temperature and light. Drug concentrations were determined by high-performance liquid chromatographic assay methods. Ceftriaxone retained greater than 90% of its original concentration for 24 hours in single-drug admixtures in NS, for eight hours with clindamycin in NS, and for one hour with clindamycin in D5W. Ceftazidime retained greater than 90% potency for 24 hours with clindamycin in D5W. In all other test admixtures, all drugs were stable for 48 hours. Under the conditions studied, clindamycin is compatible in the admixtures tested with aztreonam and piperacillin. Admixtures of clindamycin and ceftazidime in D5W should be used within 24 hours at room temperature. Clindamycin and ceftriaxone can be mixed in NS if administered within eight hours, but ceftriaxone is stable for only one hour in combination with clindamycin in D5W.

Aztreonam↗
PubMed1995

Haemodynamic and metabolic effects in diabetic ketoacidosis in rats of treatment with sodium bicarbonate or a mixture of sodium bicarbonate and sodium carbonate.

To examine factors determining the haemodynamic and metabolic responses to treatment of diabetic ketoacidosis with alkali, groups of anaesthetised and ventilated rats with either diabetic ketoacidosis (mean arterial pH 6.86-6.96, mean arterial blood pressure 63-67 mm Hg) or hypovolaemic shock due to blood withdrawal (mean pHa 7.25-7.27, mean arterial blood pressure 36-41 mm Hg) were treated with sodium chloride ('saline'), sodium bicarbonate or 'Carbicarb' (equimolar bicarbonate plus carbonate). In the diabetic ketoacidosis series, treatment with either alkali resulted in deterioration of mean arterial blood pressure and substantial elevation of blood lactate, despite a significant rise in myocardial intracellular pH determined by 31P-magnetic resonance spectroscopy. These effects were accompanied by falling trends in the ratios of myocardial phosphocreatine and ATP to inorganic phosphate. Erythrocyte 2,3-bisphosphoglycerate was virtually absent in animals with diabetic ketoacidosis of this severity and duration. In contrast, in shock due to blood withdrawal, infusion of saline or either alkali was accompanied by a transient elevation of mean arterial blood pressure and no significant change in the already elevated blood lactate; erythrocyte 2,3-bisphosphoglycerate was normal in these animals. The effect of alkalinization in rats with severe diabetic ketoacidosis was consistent with myocardial hypoxia, due to the combination of very low initial erythrocyte 2,3-bisphosphoglycerate, alkali-exacerbated left shift of the haemoglobin-oxygen dissociation curve and artificial ventilation. No evidence was found for any beneficial effect of 'Carbicarb' in either series of animals; 'Carbicarb' and sodium bicarbonate could be deleterious in metabolic acidosis of more than short duration.

3-Hydroxybutyric Acid↗
PubMed1975

A comparison on natriuresis after oral and intravenous sodium loading in sodium-depleted rabbits: evidence for a gastrointestinal or portal monitor of sodium intake.

1. Rabbits in balance on a low sodium diet were given doses of sodium chloride either orally or intravenously. 2. Those receiving oral doses responded with a much greater natriuresis than those receiving intravenous ones. 3. This could be explained by the existence of a sodium input monitor somewhere in the gut or portal circulation.

Administration, Oral↗
PubMed1984

Sodium-coupled sugar transport: effects on intracellular sodium activities and sodium-pump activity.

Intracellular sodium activities, (Na)c, were determined in Necturus small intestine before and after addition of galactose to the mucosal bathing solution. In the absence of galactose, (Na)c averaged 12 millimoles per liter. Within 2 minutes after the addition of galactose to the mucosal solution, (Na)c increased to a mean value of 20 millimoles per liter and then declined, in parallel with an increase in transcellular sodium transport, to a value that did not differ significantly from that observed in the absence of the sugar. The final steady state in the presence of galactose was characterized by a three- to fourfold increase in the rate of transcellular Na+ transport in the absence of a significant increase in (Na)c. Thus, the increase in steady-state basolateral pump activity cannot be attributed to an increase in the intracellular sodium transport pool.

Animals↗
PubMed1968

Effect of sodium nitrite, sodium chloride , and sodium nitrate on germination and outgrowth of anaerobic spores.

The effects of meat-curing agents on germination and outgrowth of putrefactive anaerobe 3679h (PA 3679h) spores were studied in microcultures. Nitrite concentrations up to 0.06% at pH 6.0 or between 0.8 and 1% at pH 7.0 allowed emergence and elongation of vegetative cells but blocked cell division. The newly emerged cells then lysed. With more than 0.06% nitrite at pH 6.0 or more than 0.8 to 1% at pH 7.0, the spores lost refractility and swelled, but vegetative cells did not emerge. Even as much as 4% nitrite failed to prevent germination (complete loss of refractility) and swelling of the spores. Sodium chloride concentrations above 6% prevented complete germination (i.e., the spores retained a refractile core). In the presence of 3 to 6% sodium chloride, most of the spores germinated and produced vegetative cells, but cell division was often blocked. Sodium nitrate had no apparent effect on germination and outgrowth at concentrations up to 2%.

Bacteria↗
PubMed2003

Endocrine disorders of sodium regulation. Role of adrenal steroids in genetic defects causing sodium loss or sodium retention.

Salt and water homoeostasis is tightly regulated by a variety of control mechanisms with the adrenal steroid hormone aldosterone playing a central role. Defects or disturbances in these systems lead to either salt loss, which is life threatening in the neonatal period, or sodium retention causing hypertension. Rapid and accurate diagnosis is required to avoid severe complications. During the last few years molecular genetic advances have been identified as the basic genetic defects for a number of clinical syndromes. This knowledge has considerably increased our understanding of the basic pathways involved in sodium and water homoeostasis and of the pathophysiology of these syndromes, particularly the hypertension. In this review we have summarized the biochemical, physiological and genetic basis for clinical syndromes presenting with salt loss and failure to thrive as well as the rare but important genetic syndromes causing sodium retention and hypertension. Early diagnosis and identification will help to prevent severe complications, but it has to be emphasized that the complicated cascade of aldosterone action is still relatively poorly understood. Further syndromes may exist which once identified will help to better understand the basic physiology of aldosterone action.

Adrenal Cortex Hormones↗
PubMed1978

Light-scattering studies on bile acid salts II: pattern of self-association of sodium deoxycholate, sodium taurodeoxycholate, and sodium glycodeoxycholate in aqueous electrolyte solutions.

The pattern of self-association of the bile salts sodium deoxycholate, sodium glycodeoxycholate, and sodium taurodeoxycholate was investigated in aqueous electrolyte solutions by the light-scattering technique. The turbidity of the bile salt solutions was obtained over the concentration range of 0-20 mg/ml at 25 degrees. These data were analyzed according to a monomer-micellar equilibrium model and a stepwise association model. Comparison of the light-scattering data with these models suggests that the monomer-micellar model may be inappropriate. Analysis of the data according to the stepwise association model suggests that the dihydroxy bile salts associate to form dimers, trimers, and tetramers in addition to a larger aggregate which varies in size depending on the degree of conjugation of the bile salt.

Chemical Phenomena↗
PubMed2006

The use of poly(sodium N-undecanoyl-L-leucylvalinate), poly(sodium N-undecanoyl-L-leucinate) and poly(sodium N-undecanoyl-L-valinate) surfactants as chiral selectors for determination of enantiomeric composition of samples by multivariate regression modeling of fluorescence spectral data.

Steady-state fluorescence spectroscopy was employed to investigate the use of chiral polymeric surfactants as chiral selectors in chiral analysis by multivariate regression modeling of spectral data. Partial-least-squares regression modeling (PLS-1) was used to correlate changes in the fluorescence spectral data of 1,1'-bi-2-naphthol (BOH), 1,1'-binaphthyl-2,2'-diamine (BNA), or 2,2,2-trifluoroanthrylethanol (TFA) in the presence of poly(sodium N-undecanoyl-L-leucylvalinate), poly(sodium N-undecanoyl-L-leucinate) or poly(sodium N-undecanoyl-L-valinate) as the enantiomeric composition of the chiral analytes was varied. The regression models produced from the spectral data were validated by determining the enantiomeric composition of independently prepared test solutions. The ability of the model to correctly predict the enantiomeric composition of future samples was evaluated using the root-mean-square percent-relative error (RMS%RE) of prediction. In terms of RMS%RE, the ability of the model to accurately predict the enantiomeric composition of future samples was dependent on the chiral analyte, the polymeric surfactant used, and the surfactant medium, and ranged between 1.57 and 6.10%. Chiral analyte concentrations as low as 5 x 10(-6) M were found to give regression models with good predictability.

Anthracenes↗
PubMed1988

Compatibility of clindamycin phosphate with aztreonam in polypropylene syringes and with cefoperazone sodium, cefonicid sodium, and cefuroxime sodium in partial-fill glass bottles.

The stability and compatibility of clindamycin phosphate admixed with four beta-lactams, an experimental monobactam (aztreonam), and three cephalosporins (cefoperazone sodium, cefonicid sodium, and cefuroxime sodium), were studied. Aztreonam alone and the combination of clindamycin phosphate-aztreonam were prepared in duplicate polypropylene syringes. Each cephalosporin antibiotic as well as the three clindamycin phosphate-cephalosporin combinations were admixed in duplicate 100 ml partial-fill glass bottles containing either dextrose 5% in water or NaCl 0.9%. All solutions were examined, antibiotic concentrations were determined, and pH was measured at the time of admixture and 1, 4, 8, 12, 24, and 48 hours later. The solutions were maintained at room temperature under fluorescent lighting for the length of the study. Antibiotic concentrations were determined by drug-specific high performance liquid chromatographic assays. Significant instability or incompatibility was defined as a decrease in concentration of greater than ten percent relative to the initial concentration measured at the time of admixture. All antibiotics were stable for 48 hours. In the combination studies, clindamycin was stable for 48 hours, both in partial-fill glass bottles and syringes. Aztreonam, cefoperazone, cefonicid, and cefuroxime were also stable for 48 hours.

Aztreonam↗
PubMed1994

Sodium channel blockade reduces hypoxic sodium loading and sodium-dependent calcium loading.

BACKGROUND: Studies have shown that the rise in intracellular ionized calcium, [Ca2+]i, in hypoxic myocardium is driven by an increase in sodium, [Na+]i, but the source of Na+ is not known. METHODS AND RESULTS: Inhibitors of the voltage-gated Na+ channel were used to investigate the effect of Na+ channel blockade on hypoxic Na+ loading, Na(+)-dependent Ca2+ loading, and reoxygenation hypercontracture in isolated adult rat cardiac myocytes. Single electrically stimulated (0.2 Hz) cells were loaded with either SBFI (to index [Na+]i) or indo-1 (to index [Ca2+]i) and exposed to glucose-free hypoxia (PO2 < 0.02 mm Hg). Both [Na+]i and [Ca2+]i increased during hypoxia when cells became inexcitable following ATP-depletion contracture. The hypoxic rise in [Na+]i and [Ca2+]i was significantly attenuated by 1 mumol/L R 56865. Tetrodotoxin (60 mumol/L), a selective Na(+)-channel blocker, also markedly reduced the rise in [Ca2+]i during hypoxia and reoxygenation. Reoxygenation-induced cellular hypercontracture was reduced from 83% (45 of 54 cells) under control conditions to 12% (4 of 32) in the presence of R 56865 (P < .05). Lidocaine reduced hypercontracture dose dependently with 13% of cells hypercontracting in 100 mumol/L lidocaine, 42% in 50 mumol/L lidocaine, and 93% in 25 mumol/L lidocaine. The Na(+)-H+ exchange blocker, ethylisopropylamiloride (10 mumol/L) was also effective, limiting hypercontracture to 12%. R 56865, lidocaine, and ethylisopropylamiloride were also effective in preventing hypercontracture in normoxic myocytes induced by 75 mumol/L veratridine, an agent that impairs Na+ channel inactivation. Ethylisopropylamiloride prevented the veratridine-induced rise in [Ca2+]i without affecting Na(+)-Ca2+ exchange, suggesting that amiloride derivatives can reduce Ca2+ loading by blocking Na+ entry through Na+ channels, an action that may in part underlie their ability to prevent hypoxic Na+ and Ca2+ loading. CONCLUSIONS: Na+ influx through the voltage-gated Na+ channel is an important route of hypoxic Na+ loading, Na(+)-dependent Ca2+ loading, and reoxygenation hypercontracture in isolated rat cardiac myocytes. Importantly, the Na+ channel appears to serve as a route for hypoxic Na+ influx after myocytes become inexcitable.

Amiloride↗