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PubMed1998

Randomized long-term evaluation of bicarbonate-buffered CAPD solution.

BACKGROUND: Over the past 15 years, lactate has been used successfully as a buffer in peritoneal dialysis solutions, although its effectiveness in the correction of uremic acidosis and its biocompatibility on peritoneal resident cells have been questioned. In addition, some investigators have suggested other potential adverse metabolic effects resulting from the unphysiologically high lactate flux into the body during CAPD. These potential problems associated with lactate-containing CAPD solution prompted the search for alternative buffer-containing solutions. Bicarbonate, the physiological buffer, was considered when the problem of calcium and magnesium carbonate solubility was solved by the use of a two-compartment bag system, allowing the mixing of bicarbonate and divalent cations immediately before infusion. The long-term tolerance, safety, efficacy and therapeutic value of a bicarbonate-buffered peritoneal dialysis solution were evaluated in this study. METHODS: This open, randomized, controlled, multicenter study comparing a 34 mmol/liter bicarbonate- with a 35 mmol/liter lactate-buffered peritoneal dialysis solution was performed in two consecutive 12-week-treatment phases. Fourteen Centers participated in this trial. RESULTS: A total of 69 out of initially 123 randomized patients completed the six-month study period (36 patients in the bicarbonate group and 33 in the lactate group). While the arterial acid base status of the total study population did not change during the study period and no significant difference was observed between the two treatment groups, the acid-base status of patients in the bicarbonate group entering the study with a metabolic acidosis significantly improved (mean +/- SD; blood pH: baseline = 7.361 +/- 0.05, week 12 = 7.380 +/- 0.04, P < 0.05; week 24 = 7.388 +/- 0.03 P < 0.05; plasma bicarbonate: baseline = 19.49 +/- 3.01 mmol/liter, week 12 = 21.16 +/- 2.63 mmol/liter, P < 0.01; week 24 = 21.51 +/- 2.42 mmol/liter, P < 0.01). No significant changes were recorded in acidotic patients treated with the conventional lactate-buffered solution. The changes in plasma bicarbonate from baseline during the study was significantly different between the groups (week 12: lactate = +0.11 +/- 2.21 mmol/liter, bicarbonate = +1.69 +/- 2.55 mmol/liter, P < 0.05, 95% confidence interval for the difference 0.21 to 2.94 mmol/liter; week 24: lactate = +0.03 +/- 2.48 mmol/liter, bicarbonate = +1.82 +/- 2. 96 mmol/liter, P < 0.05, 95% confidence interval for the difference 0.16 to 3.42 mmol/liter). The normalized protein catabolic rate (nPCR) slightly but significantly decreased in the lactate group (baseline -0.90 +/- 0.23 g/kg/day, week 24 -0.83 +/- 0.21 g/kg/day, P < 0.01) and increased in the bicarbonate group (baseline +0.89 +/- 0.28 g/kg/day, week 24 +0.92 +/- 0.26 g/kg/day, P < 0.05). Changes from baseline between groups were significant (week 24, lactate = -0. 099 +/- 0.15 g/kg/day, bicarbonate = 0.049 +/- 0.12 g/kg/day, P < 0. 01, 95% confidence interval for the difference 0.068 to 0.229 g/kg/day). Other evaluated parameters (biochemical profile, peritoneal function parameters, dialysate protein loss) did not differ significantly between the two groups. No adverse effects related to the study solution were recorded. CONCLUSIONS: These results support the efficacy and safety of bicarbonate-buffered peritoneal solutions in a controlled randomized comparison for up to six months. Peritoneal dialysis solutions containing the physiological buffer bicarbonate might effectively replace conventional lactate-buffered CAPD solutions.

Acid-Base Equilibrium↗
PubMed2001

Kinetic studies of dipeptide-based and amino acid-based peritoneal dialysis solutions.

BACKGROUND: Dipeptide-based peritoneal dialysis solutions may have potential advantages compared with the glucose or amino acid-based solutions. Dipeptides may hydrolyze in the peritoneal cavity, generating constituent amino acids and thereby increasing the osmolality of the dialysate. Dipeptides can also be a valuable source of amino acids, which are poorly soluble in water, such as tyrosine. METHODS: Dwell studies in rats were performed during four hours with dipeptide solutions containing five dipeptides (Gly-His, Ala-Tyr, Thr-Leu, Ser-Phe, Val-Lys), 8, or 16 mmol/L of each dipeptide (low or high dipeptide group). Dwell studies were also performed with a 1.1% amino acid solution (Nutrineal(R)). The model of dipeptide hydrolysis (hydrolysis rate, KH), diffusive (rate constant, KBDD) and convective transport as well as transport of constituent amino acids consisted of mass balance equations, written for each dipeptide and amino acid. RESULTS: Peritoneal volume with the amino acid solution decreased much faster than that with the high and low dipeptide solutions. KH for all dipeptides did not differ between the high and low dipeptide groups. In the low dipeptide group, KH was 0.004 +/- 0.004 mL/min (mean +/- SD) for Gly-His (the lowest) and 0.088 +/- 0.048 mL/min for Thr-Leu (the highest). KBDD was higher than KH for all dipeptides, the average being 0.2 +/- 0.05 mL/min. CONCLUSIONS: Dipeptides are hydrolyzed in the peritoneal cavity, generating constituent amino acids. However, the hydrolysis rate appears to be several times lower than the dipeptide diffusive transport rate from dialysate to blood. Due to the higher molecular weight and intraperitoneal generation of amino acids, the dipeptide-based solutions provide more sustained ultrafiltration than the amino acid solution. The plasma concentration of amino acids at 60 minutes, in relation to the dose of amino acids delivered between 0 and 60 minutes, is considerably higher during the dwells with amino acid-based solution than during dwells with the dipeptide-based solutions.

Amino Acids↗
PubMed2001

Antibacterial effect of antibiotic solution on cellular viability in canine veins.

Pretreatment of tissue by using antibiotics is a critical step to prevent microbial contamination before venous transplantation. In this study, the optimal time and temperature of antibiotic solution treatment for maintaining cellular viability with antibacterial effect were investigated. The antibiotic-nutrient solutions were composed of cefoxitin, lincomycin, vancomycin, and polymyxin B in RPMI-1640 medium. After various antibiotic solution treatment times (4, 8, and 12 h) and temperatures (4, 25, and 37 degrees C), the viabilities of cells dissociated from veins (jugular vein, femoral vein, superior vena cava, and inferior vena cava) were determined. Double staining by Griffonia simplicifolia agglutins-fluorescein isothiocyanate (GS1-FITC) and propidium iodide was used. To measure the antibacterial effect of the antibiotic solution, canine veins were artificially infected by 3 kinds of bacteria (Staphylococcus aureus, Escherichia coli, and Klebsiella pneumoniae) and were treated by antibiotic solutions as viability test conditions. After the treatment with the antibiotic solution, the tissue was minced, and the homogenized tissue fraction was cultured on standard method agar. The colony that seemed to be resistant to the antibiotic solution was counted. At 37 and 25 degrees C, the viability of whole cells decreased significantly Asymptotic Significance 2-tailed (Asymp.Sig 2-tailed) < 0.05 after 4 h of antibiotic solution treatment, whereas at 4 degrees C it began to reduce significantly after 8 h of treatment. By antibiotic solution treatment at all 3 temperatures for 4 h, no significant difference in viability of the endothelial cells and whole cells was observed. To maintain the donor vein's cellular viability until transplantation, antibiotic solution treatment for 4 h at 4 degrees C is assumed to be appropriate.

Animals↗
PubMed2000

Glutathione, lactobionate, and histidine: cryptic inhibitors of matrix metalloproteinases contained in University of Wisconsin and histidine/tryptophan/ketoglutarate liver preservation solutions.

UW solution and HTK solution are both used for cold preservation of liver allografts. Although they are about equally effective, their compositions are very different, and they were formulated using different rationales. The authors recently showed an important role for MMPs in liver preservation injury and consequently postulated that these preservation solutions contain cryptic inhibitors of MMP activity. To determine this possibility, the ability of these solutions to inhibit MMP activity was studied. The source of MMP2 and MMP9 was human liver effluents obtained at the time of liver transplantation or commercially available human recombinant MMP2 and MMP9. MMP2 and MMP9 showed gelatinolytic activity at 37 degrees C and also at 4 degrees C, although activity at 4 degrees C was reduced. Activity was inhibited by University of Wisconsin (UW) and Histidine/Tryptophan/ Ketoglutarate (HTK) solutions. Examination of individual ingredients disclosed that reduced glutathione (GSH) and lactobionate in UW solution and histidine in HTK solution were the cryptic inhibitors. HTK solution was a more effective inhibitor than UW solution. GSH inhibited the activity of both enzymes, but was a much more effective inhibitor of MMP9 than MMP2. Oxidized glutathione(GSSG) was a much less effective inhibitor of the enzymes. The inhibitor constants (K(i)) of GSH for MMP2 and MMP9 were 34 micromol/L and 3 micromol/L, respectively. The authors conclude that MMP inhibition is a cryptic property of both commonly used liver preservation solutions and contributes importantly to their action. Furthermore, GSH appears to be an effective inhibitor of gelatinases at concentrations at which it is normally present in extracellular fluid.

Adenosine↗
PubMed1977

Inhibition by hypertonic solutions of Ca-dependent electrogenesis in single crab muscle fibers.

This study describes the effect of hypertonic solutions on isolated muscle fibers of Callinectes danae. Solutions of twice normal tonicity (2.0 T) inhibit both the normal graded membrane responses and the spikes induced by procaine, tetraethylammonium, or barium. The inhibition is maintained throughout exposure to hypertonic solutions prepared by addition of impermeant solutes such as NaCl, sucrose, or Tris-propionate, but is reversible on their withdrawal. In the presence of permeant solutes such as glycerol or acetamide, the inhibition is transient. In both cases the onset of inhibition of the depolarizing Ca electrogenesis is correlated with shrinkage of the fiber. In the case of permeant solutes, the time course of recovery of the graded responses or the spikes follows the recovery of the fiber volume. Changes in the passive electrical characteristics of the fibers due to hypertonic solutions were unrelated to the blockade of membrane Ca activation. The current-voltage relationship in hypertonic sollution revealed no increase in depolarizing K activation. Inhibition of the graded membrane responses and spikes appears to be associated with depression of Ca conductance. Hypertonic solutions might affect the activation of Ca conductance through reduction of the electric field generated by fixed negative surface charges and/or morphological changes in the T tubules. Membrane depolarization elicited little or no tension in 2.0 T solutions while caffeine contracture (10 mM) with an ampliture of 76% of the maximal contractile ability could still be elicited. This indicates that direct effects of hypertonic solutions on the contractile apparatus were not responsible for loss of tension. The latter is attributed to the inhibition of the transmembrane Ca currents.

Acetamides↗
PubMed2006

Pyrogenic reactions and hemorrhage associated with intrinsic exposure to endotoxin-contaminated intravenous solutions.

OBJECTIVE: An epidemiological investigation was conducted to determine risk factors for adverse reactions among patients in hospitals and the possibility of extrinsic or intrinsic contamination of intravenous solutions. DESIGN: A retrospective cohort study was conducted to identify solutions associated with adverse reactions. Implicated lots were cultured for bacteria, and endotoxin concentrations were measured. SETTING: Five hospitals in the state of Pernambuco, Brazil, were investigated from February through March 2002. PATIENTS: Surgical inpatients or outpatients receiving intravenous solutions during the study period. RESULTS: Of 355 surgical patients or outpatients treated at hospitals, 28 (8%) developed illness within a mean of 2.5 hours after exposure to intravenous solutions implicated in adverse reactions; 5 (17.9%) of the case patients died. Laboratory testing of bottles from the lots of Ringer's lactate solution implicated in deaths demonstrated a high mean endotoxin concentration of 88.3 endotoxin units (EU)/mL (range, 9.7-298.0 EU/mL), compared with the permitted limit in Brazil of <0.5 EU/mL. Testing of metronidazole implicated in adverse reactions at another hospital and produced by the same company that manufactured the lots Ringer's lactate solution also showed high endotoxin concentrations (mean level, 8.3 EU/mL [range, 5.0-58.3 EU/mL]). The outbreak was controlled after a national recall of the implicated brand of intravenous solutions. CONCLUSIONS: Case patient status was associated with use of Ringer's lactate solution and metronidazole from large bottles, both of which were produced by the same company. High endotoxin concentrations were demonstrated in unopened bottles of implicated products, which is consistent with intrinsic contamination. The high mortality rate may have been compounded by the fact that clinicians administered additional volumes of contaminated 0.9% isotonic sodium chloride solution in response to hypotension or bleeding to some surgical patients. No additional case patients were identified after a national recall of products, inspection, closure of the implicated company's manufacturing facility, and establishment of random quality-control testing of intravenous solutions.

Cohort Studies↗
PubMed2003

Acute effect of amino acid peritoneal dialysis solution on vascular function.

BACKGROUND: Oral ingestion of proteins or amino acids is associated with endothelial dysfunction. The effect of commercial amino acid peritoneal dialysis solutions on vascular function is unknown. OBJECTIVE: We compared the acute effect of intraperitoneal amino acid administration with that of intraperitoneal glucose administration on vascular function in peritoneal dialysis patients. DESIGN: In an open-label randomized, controlled, crossover and observer-blinded trial, we examined the acute effect of an intraperitoneal application of 2 L commercial 1.1% amino acid solution compared with that of a 2.27% glucose solution in 13 peritoneal dialysis patients. The primary endpoint was the change in forearm reactive hyperemia 6 h after instillation of either dialysis solution. RESULTS: After 6 h of dwell time, reactive hyperemia was substantially impaired after administration of the amino acid solution compared with the glucose solution (median difference: 202%; 95% CI: 57%, 368%; P = 0.007). In a comparison of differences between values at 6 h and those before treatment, reactive hyperemia significantly decreased during the dwell with the amino acid dialysis solution compared with that with the glucose dialysis solution (median difference: 242%; 95% CI: 53%, -457%; P = 0.013). In an analysis of smoking and nonsmoking patients separately, the difference in forearm blood flow between the 2 treatments was still statistically significant. CONCLUSIONS: One 6-h dwell with a commercial amino acid dialysis solution acutely impairs forearm reactive hyperemia in smoking and nonsmoking peritoneal dialysis patients. Because endothelial dysfunction is associated with increased morbidity and mortality, the long-term use of these solutions may increase the risk of cardiovascular disease.

Adult↗
PubMed2004

Analysis of phthalate contamination in infusion solutions by automated on-line in-tube solid-phase microextraction coupled with high-performance liquid chromatography.

Contamination of infusion solutions with phthalates was analyzed, and its origin was determined. Phthalates were determined by on-line in-tube solid-phase microextraction coupled with high-performance liquid chromatography (in-tube SPME-HPLC) with UV detection. In-tube SPME is an extraction technique for organic compounds in aqueous samples, in which analytes are extracted from the sample directly into an open tubular capillary by repeated draw/eject cycles of sample solution. The infusion solutions were used without any pretreatment, and the phthalates in these solutions were automatically analyzed by the on-line in-tube SPME-HPLC system. The limits of detection of phthalates in the infusion solutions were 1-10 ng/mL. With a few exceptions, the recoveries of phthalates added to the infusion solutions were above 80%. Di-n-butyl phthalate (DBP) was detected at a concentration of 7-60 ng/mL in most infusion solutions in plastic containers but was not detected in those in glass bottles. On the other hand, no other phthalates were detected in infusion solutions in either plastic or glass containers. Large amounts of DBP were detected in the adhesive used to affix the paper labels to the plastic bottles and bags, but not in the plastic containers themselves. Furthermore, DBP was shown to be readily eluted from the adhesive into water and alcohol and easily pass through the plastic. These results indicated that the source of the DBP was the adhesive used to affix the paper labels, and DBP contaminated the infusion solutions by passing through the plastic. The in-tube SPME-HPLC method is simple and rapid and provides a useful tool for the screening and determination of phthalate contamination in infusion solutions.

Adhesives↗
PubMed2005

Not so crystal clear: the structure of the human telomere G-quadruplex in solution differs from that present in a crystal.

The structure of human telomere DNA is of intense interest because of its role in the biology of both cancer and aging. The sequence [5'-AGGG(TTAGGG)3] has been used as a model for telomere DNA in both NMR and X-ray crystallographic studies, the results of which show dramatically different structures. In Na+ solution, NMR revealed an antiparallel G-quadruplex structure that featured both diagonal and lateral TTA loops. Crystallographic studies in the presence of K+ revealed a flattened, propeller-shaped structure featuring a parallel-stranded G-quadruplex with symmetrical external TTA loops. We report the results of biophysical experiments in solution and computational studies that are inconsistent with the reported crystal structure, indicating that a different structure exists in K+ solutions. Sedimentation coefficients were determined experimentally in both Na+ and K+ solutions and were compared with values calculated using bead models for the reported NMR and crystal structures. Although the solution NMR structure accurately predicted the observed S-value in Na+ solution, the crystal structure predicted an S-value that differed dramatically from that experimentally observed in K+ solution. The environments of loop adenines were probed by quantitative fluorescence studies using strategic and systematic single-substitutions of 2-aminopurine for adenine bases. Both fluorescence intensity and quenching experiments in K+ yielded results at odds with quantitative predictions from the reported crystal structure. Circular dichroism and fluorescence quenching studies in the presence of the crowding agent polyethylene glycol showed dramatic changes in the quadruplex structure in K+ solutions, but not in Na+ solutions, suggesting that the crystal environment may have selected for a particular conformational form. Molecular dynamics simulations were performed to yield model structures for the K+ quadruplex form that are consistent with our biophysical results and with previously reported chemical modification studies. These models suggest that the biologically relevant structure of the human telomere quadruplex in K+ solution is not the one determined in the published crystalline state.

2-Aminopurine↗
PubMed2006

Changing prescribing practice in CAPD patients in Korea: increased utilization of low GDP solutions improves patient outcome.

BACKGROUND: Novel, biocompatible peritoneal dialysis (PD) solutions have become available in recent years. In 2001, low glucose degradation products (GDP), neutral pH solutions became commercially available in Korea. To date, there are no reports regarding the large scale adoption of these solutions in clinical practice and regarding what, if any, impact these solutions have on patient outcomes. METHODS: Using a database of almost 4000 patients treated by PD in Korea, we conducted a prospective, longitudinal observational study documenting the patterns of use of one novel low GDP solution (balance, Fresenius Medical Care, St Wendel, Germany) in 1909 PD incident patients between 1 January 2002 and midyear 2005. Outcomes including patient and technique survival and peritonitis rates were analysed using univariate and multivariate analysis. RESULTS: Prescription of low GDP solutions reached between 70 and 80% by the year 2003 and persisted at this level. Patients prescribed low GDP PD solution tended to be younger and were more likely to be treated in centres with larger enrollment in the database. Survival of diabetic patients treated with the new PD solution was identical to that of the non-diabetic patients treated with standard PD fluids (PDF) and treatment with low GDP PDF independently reduced the relative risk (RR) of death (RR = 0.613; CI 0.50-0.74; P < 0.00001) in a proportional hazards model which included age, diabetes and centre experience. In a univariate analysis, low GDP PD solution was associated with a longer technique survival (P = 0.049) but this effect was not significant in multivariate analysis. No significant differences in peritonitis-free interval or peritonitis rate could be attributed to the prescribed PDF. CONCLUSION: Prescription of low GDP, pH-neutral PD solutions has rapidly increased in Korea. This change has resulted in a significant improvement in patient and technique survival without any measurable change in peritonitis incidence or rate. Reasons for the improved patient survival cannot be determined from this analysis and require further study.

Adult↗
PubMed1995

Ciliary beat frequency of hamster oviducts is decreased in vitro by exposure to solutions of mainstream and sidestream cigarette smoke.

Epidemiological data support a correlation between smoking and increased incidence of ectopic pregnancy, yet the causal mechanism responsible for this relationship is unknown. The purpose of this study was to examine the effect of solutions containing dissolved mainstream (MS) or sidestream (SS) cigarette smoke on ciliary beat frequencies (CBF) in explants of hamster oviducts. MS smoke is the puff inhaled by an active smoker, while SS smoke leaves the burning end of cigarette. SS smoke is inhaled by both active and passive smokers. Experiments were performed in handmade perfusion chambers using infundibula from hamster oviducts. After a short incubation in Earle's balanced salt solution containing HEPES buffer (EBSS-H), chambers were flushed with one of six types of smoke solution prepared in EBSS-H, and incubation continued 19 min. A second perfusion (washout) was then done using EBSS-H alone to determine whether effects induced by the smoke solutions could be reversed. CBF were determined at three times in both the smoke and washout solutions, and means were compared to values obtained in the initial EBSS-H incubation. All smoke solutions except the SS particulate solution inhibited CBF in a dose-dependent manner. Whole MS and whole SS smoke solution at the highest strength tested caused the greatest inhibition and in some cases completely stopped ciliary beating. Both single-strength and 0.1-strength MS gas phase solutions, which contained concentrations of nicotine in the range found in typical human smokers, produced about 50% inhibition of ciliary beating. Inhibition was generally seen within 2-12 min of adding smoke solutions.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1998

Variations in the composition of spinal anesthetic solutions: the effects of drug addition order and preparation methods.

UNLABELLED: Adjuvants such as opioids or epinephrine are commonly added in small volumes to multicomponent spinal anesthetic solutions. In this study, we tested the hypothesis that final adjuvant concentrations vary depending on the devices and techniques used to prepare the anesthetic solution. We compared two aspiration devices, the filter needle and the filter straw, in a laboratory study. Two techniques for drawing up and estimating adjuvant volumes were assessed, as was variation in the composition of a model spinal anesthetic solution resulting from intra- and interindividual variability. A model hyperbaric anesthetic solution consisting of tetracaine, dextrose, and methylene blue (MB) as a small-volume tracer solution was studied. The components were drawn up into a syringe through one of two commercially supplied aspiration devices, a filter straw or a filter needle. The effect of the order of aspiration of the components into the syringe was measured by determining the MB concentration in the final solution by optical absorbance. Ten experienced anesthesiologists then prepared samples of the test solution using one of two different techniques to estimate tracer volume in the aspiration syringe. In comparison studies, the MB tracer was added to the hyperbaric solution with a tuberculin syringe. The order of aspiration of the solution components had a large effect on the final concentration of the MB tracer in the ultimate mixture. Variation in the MB concentration was on the order of four- to fivefold. Effects were larger for the filter straw compared with the filter needle. A comparison of 10 anesthesiologists revealed large intra- and interindividual variations in the final composition of the model anesthetic solution. The concentration of tracer added to the mixture with a tuberculin syringe approximated the planned yield. We conclude that the devices and techniques used to prepare mixtures of drugs for delivery to the cerebrospinal fluid may influence the concentrations of drugs in the anesthetic and, thus, the dose supplied to the patient receiving spinal anesthesia. Variation in clinical effects of spinal anesthetics may be attributable, in part, to variation in the composition of the anesthetic. IMPLICATIONS: This laboratory study demonstrates the potential for large variation in the composition of spinal anesthetic mixtures.

Adjuvants, Anesthesia↗
PubMed1983

Osmolarity determines the solubility of anesthetics in aqueous solutions at 37 degrees C.

The authors determined whether they could predict accurately the solubility of anesthetics in aqueous solutions at 37 degrees C, knowing the osmolarity and the pH of the solution and the solute composition. The partition coefficients of the four volatile anesthetics, isoflurane, enflurane, halothane, and methoxyflurane, were determined concurrently at 37 degrees C between air and aqueous solutions containing sodium chloride, dextrose, mannitol, or heparin. The osmolarities of these solutions ranged from 0 to 7,000 mOsm/l. The partition coefficients decreased linearly with increasing osmolarity when plotted on a semilogarithmic scale. The effect of osmolarity on the partition coefficient of the alkane anesthetic, halothane, was 20% less (P less than 0.001) than the effect of osmolarity on the partition coefficients of the three methyl-ethyl ether anesthetics, isoflurane, enflurane, and methoxyflurane. The solubility of anesthetics in aqueous solutions did not depend on either the molecular structure of the solute or the pH of the solution. The solubility of volatile anesthetics in aqueous solutions at 37 degrees C is inversely and predictably dependent on the osmolarity of the solutions.

Anesthetics↗
PubMed1997

Effect of intravenous lactated Ringer's solution infusion on the circulating lactate concentration: Part 3. Results of a prospective, randomized, double-blind, placebo-controlled trial.

OBJECTIVES: We previously discovered that small amounts of lactated Ringer's solution, which are inadequately cleared from an intravenous catheter, falsely increase the circulating lactate concentration in blood samples collected from that catheter. That finding prompted us to test the hypothesis that intravenous lactated Ringer's solution, infused at a rate used in resuscitation, would increase the circulating lactate concentration. DESIGN: A prospective, randomized, double-blinded, placebo-controlled study. SETTING: A critical care research laboratory. SUBJECTS: Twenty-four normal, healthy, adult volunteer subjects. INTERVENTIONS: Two intravenous catheters were placed. One was used for the infusion of the test solution and the other catheter was used for blood sampling. Blood samples were serially collected for the determination of blood lactate concentrations. MEASUREMENTS AND MAIN RESULTS: Twenty-four healthy adult volunteers were randomized to receive a 1-hr infusion of either lactated Ringer's solution (n = 6), 0.9% saline (n = 6), 5% dextrose in lactated Ringer's solution (D5RL) (n = 6), or 5% dextrose in water (D5W) (n = 6). Each subject received nothing by mouth after midnight. At 0800 hrs, catheters were inserted and each subject received 1 L of the assigned solution over 1 hr. Throughout the study, the subjects were at rest. Three-milliliter samples of venous blood were collected before, during (at 15, 30, 45, and 60 mins), and after (at 90, 120, and 240 mins) the infusion. Blood samples were placed on ice immediately after collection and analyzed within 5 mins of collection. Lactate concentrations were determined using an ion-selective, amperometric electrode, which we have previously validated. Lactate concentrations were compared between subjects receiving lactated Ringer's solution vs. subjects receiving normal saline. A similar comparison was made between subjects receiving D5RL vs. D5W at similar time points during the study. There were no clinically or statistically significant differences in lactate values at the time points studied in those subjects receiving lactated Ringer's solution vs. those persons receiving normal saline (p > .05; n = 12; Student-Newman-Keuls' multiple comparison test) or those subjects receiving D5W vs. those subjects infused with D5RL (p > .05; n = 12; Student-Newman-Keuls' multiple comparison test). In no case did the circulating lactate values exceed 2 mmol/L (the upper limit of normal). CONCLUSIONS: The short-term infusion of lactated Ringer's solution in normal adults (hemodynamically stable) does not falsely increase circulating lactate concentrations when 1 L is given over 1 hr. Therefore, clinicians should not disregard increased lactate concentrations in patients receiving a rapid infusion of lactated Ringer's solution.

Adult↗
PubMed1996

The role of zinc in solutions used for cold preservation of pancreatic islets.

Advances in the field of organ transplantation have been made possible by progress in cold preservation as well as advances in immunosuppression, postoperative surgical care, and refinement of surgical techniques. The optimal solution for cold storage of pancreatic islets has not been defined, although recent studies have suggested that University of Wisconsin (UW) solution or derivatives may be significant advances. Zinc has a central role in the storage, synthesis, and secretion of insulin and is taken up preferentially by isolated islets to levels 30-fold higher than those of extracellular zinc. Since the currently used cold storage solutions do not contain zinc, we have investigated the effect of adding zinc to Hanks and UW solution and assessed the viability status of the islets at 0 h and at 1, 3, and 6 days. Islets of standard diameter were suspended in four solutions: Hanks solution, Hanks +20 microM zinc, UW solution, and UW +20 microM zinc. Viability was assessed by supravital staining, and each islet was scored at 0 h and at 1, 3, and 6 days. The results showed that UW solution was superior to Hanks solution for the preservation of pancreatic islets up to 6 days, but the addition of zinc was not beneficial. Despite the integral role of zinc in islet metabolism, we were unable to find a beneficial role for zinc in cold storage solutions for the purposes of islet preservation.

Animals↗
PubMed1981

Three simple solutions for renal flush and preservation.

The harvesting of kidneys at small hospitals where standard flush solutions are not available has led to the use of several flush solutions that can be made from readily available materials. Mongrel dogs (15) had bilateral nephrectomy after receiving intravenously a mixture of Ringer's lactate, furosemide (Lasix), mannitol, and chlorpromazine (Thorazine). One kidney was perfused with iced Collins' solution and stored for 24 hours, submerged in the perfusate at 4 C. Five dogs each had the contralateral kidney perfused with a solution of either (1) Ringer's lactate, salt-poor albumin, and heparin; (2) 6% dextran 70 and Fenwall buffered heparin solution; or (3) Ringer's lactate, mannitol, and heparin, and were stored in their respective perfusate. After 24 hours' storage the kidneys were transplanted into the neck, and creatinine clearance (Crcl) was determined on days 1, 2, 3, 5, and 7. The dogs were sacrificed on day 7 and biopsy specimens were obtained from each kidney for pathologic examination. The kidneys perfused with Collins' solution had immediate function after transplantation with an average Crcl of 10.5 at 25 hours and 20.2 at seven days. The kidneys perfused with Ringer's lactate and albumin had minimal function immediately after transplantation and were anuric within 24 hours. The kidneys perfused with dextran solution and Ringer's lactate and mannitol solution had immediate function but output remained low, and by seven days the average Crcl was only 3.0 and 4.5 respectively. All solutions except the Ringer's lactate and albumin were hyperosmolar, thus helping to prevent the "no reflow" phenomenon. These results indicate that the solutions tested do not result in the adequate preservation to warrant clinical use.

Animals↗
PubMed2003

Effects of contact lens care solutions on surface exfoliation and bacterial binding to corneal epithelial cells.

PURPOSE: The purpose of this study is to assess the effects of commercially available contact lens wetting solutions on bacterial binding and cell exfoliation rates in human corneal epithelium. METHODS: The effects of four contact lens care solutions were tested: ReNu Multi Plus (Bausch & Lomb, Rochester, NY) multipurpose solution; OPTI-FREE Express (Alcon, Ft. Worth, TX) multipurpose solution; Complete Blink-N-Clean (Allergan, Irvine, CA) lens drops; and Lens Plus (Allergan) rewetting drops. STUDY DESIGN: Prospective, double-masked, randomized crossover clinical trial (N = 20 subjects). OUTCOME MEASURES: Measures of outcome included binding of Pseudomonas aeruginosa (PA) to exfoliated corneal epithelial cells, and the rate of surface cell exfoliation. Cells were collected at the baseline (pretreatment) examination and 4 days later, after subjects used the assigned solution six times daily and once again immediately before cell collection (posttreatment). Following cell collection, patients underwent 1 week of recovery, during which no drops were used, and random cross-over assignment to the next test solution. RESULTS: Use of test solutions increased PA binding, with a range of + 11.9% to + 58.2%. Analyzed together, PA binding increased significantly (+ 29%; P = 0.02, paired t-test); Lens Plus solution alone raised PA binding levels significantly (P = 0.022, 2-way ANOVA, Student-Newman-Keuls [SNK] test). Exfoliation rates were decreased from -7% to -52.7%. Analyzed together, cell exfoliation decreased significantly (P = 0.004; Wilcoxon signed rank test). Individual use of OPTI-FREE decreased exfoliation significantly (P = 0.019: 2-way ANOVA, SNK test). CONCLUSIONS: Topical application of common commercial contact lens care solutions increases PA binding and reduces corneal surface cell exfoliation. Similar effects have also been reported with contact lens wear. Taken together, the data suggest that the use of lens solution itself may play a role in increasing PA binding to corneal epithelial cells and, hence, might potentially contribute inadvertently to increased risk for lens-related microbial keratitis.

Adult↗
PubMed2003

Hemoglobin solutions.

OBJECTIVE: To review current knowledge about cell-free hemoglobin solutions. DATA SOURCE: A computerized MEDLINE search was used to retrieve all studies concerning cell-free hemoglobin solutions from 1990 to 2003. The reference lists of all available review articles and primary studies were also reviewed to identify references not identified in the computerized search. STUDY SELECTION: All clinical and experimental studies involving cell-free hemoglobin solutions were included. DATA EXTRACTION: From the selected studies, information was obtained regarding the experimental model or the study population in which cell-free hemoglobin solutions were investigated, the type of cell-free hemoglobin solution used, their deleterious or beneficial effects, and their possible indications. DATA SYNTHESIS: In many studies, hemoglobin solutions were considered as efficient resuscitative agents and good alternatives to red blood cell transfusion, owing to their marked vasopressor effect, coupled with their capacity to improve the microcirculation and rapidly restore metabolic parameters. The main problems identified include excessive systemic vasoconstriction and oxidative damage. Initial enthusiasm in the development of hemoglobin solutions has been tempered recently by the negative results of a U.S. multicenter trial studying the early infusion of diaspirin cross-linked hemoglobin in trauma patients. Nevertheless, the properties of diaspirin cross-linked hemoglobin (and particularly the strong vasopressor effects) cannot be attributed to all hemoglobin solutions, and results of new clinical studies are eagerly awaited to evaluate the potential benefit of such solutions in the management of trauma patients. CONCLUSIONS: Today, we are aware of the effects of the first generation of blood substitutes. Further research is ongoing into newer solutions. One area of interest is the development of new molecular structures to decrease nitric oxide binding, thus minimizing any adverse events and maximizing potential benefits. Nevertheless, possible adverse effects need to be carefully evaluated before these agents can be widely administered.

Animals↗