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In vitro analysis of ultrasound second generation contrast agent diluted in saline solution.

PURPOSE: To evaluate the changes in response of a second-generation sonographic contrast agent diluted in saline solution at different concentrations when different scanning techniques, and saline solution temperatures and pH were used. MATERIALS AND METHODS: A series of tests was devised to analyse the behaviour of the sonographic contrast agent at different concentrations, temperatures, pH and scanning techniques. Latex balloons were used as phantoms. These were filled with 0.9% Sodium Chloride solution mixed with a suspension of sulphur hexafluoride microbubbles stabilised with phospholipids (SonoVue ) and scanned with the harmonic imaging technique at low acoustic pressure. For each image obtained, we calculated the mean grey-scale level values and the standard deviations of grey-scale level were calculated within a ROI on the US images obtained; the resulting data were used to create echogenicity curves of UCA the echo-enhancer over time at the different conditions tested. RESULTS: We noted that SonoVue maintains adequate backscatter properties even at low concentration (0.15%) in N/S solution. The amount of echogenicity can be considered adequate for the average duration of an ultrasound examination. These properties are not affected by the scanning technique used on the phantom containing the UCA contrast agent/NaCl solution. The pH of the saline solution does not affect the survival of the microbubbles. Temperature becomes a significant value beyondover 33-37 degrees C; this condition favours rupture of the microbubbles with subsequent reduction of the echogenicity after 10-15 min, and complete disappearance after 30 min. US beam attenuation related to the concentration of the microbubbles in the saline solution volume has a non-linear behaviour; at low amplification levels, attenuation becomes more significant when using SonoVue concentrations higher than 0.4%. Unexpected greater improvement in US beam transmission was experienced for each of the three SonoVue concentrations tested, and especially for 0.2% and 0.4%, compared to saline solution alone. CONCLUSIONS: Our results show that a second-generation contrast agent may be used even diluted at low concentration in saline solution. This characteristic opens up new diagnostic perspectives possibilities for the use of contrast-enhanced harmonic imaging; in particular, its can be suggested used in hollow organs and functional studies. These in vitro results require by confirmation by clinical applications which are under evaluation and experimentation.

Contrast Media↗

Stability of fluconazole and amino acids in parenteral nutrient solutions.

The stability of fluconazole and amino acids in parenteral nutrient (PN) solutions was studied. Amino acids at three concentrations (1.0%, 2.5%, and 5.0%) with 25% dextrose injection were combined with a high (1.75 mg/mL) or a low (0.5 mg/mL) concentration of fluconazole to form six combinations of PN solution and fluconazole. The solutions were visually inspected for precipitate, color change, or gas formation and tested for pH. By using high-performance liquid chromatography, the solutions were assayed for fluconazole concentration at zero, one, and two hours after preparation. The PN solution containing fluconazole 1.75 mg/mL and 5.0% amino acids was assayed for 14 amino acids at the same time points. There was no visual evidence of incompatibility in any of the fluconazole and PN solutions, and the pH of the solutions did not vary appreciably throughout the study period. The mean percentage of initial fluconazole concentration remaining at one and two hours was greater than 97% for all of the solutions studied. The mean percentage of initial amino acid concentration remaining at one and two hours was greater than 93% for each of the 14 amino acids assayed. When fluconazole 0.5 mg/mL or 1.75 mg/mL is mixed with PN solution containing 1.0%, 2.5%, or 5.0% amino acids and 25% dextrose injection, both fluconazole and amino acids are stable for up to two hours.

Amino Acids↗

[Criteria for the safety of transfusion of colloidal solutions in patients with acute lung lesions].

The prospective study explored the hemodynamic effects of colloidal solution replacement therapy and the criteria for its safety in patients with acute lung parenchymatous lesions (ALPL) attended by hypoalbuminemia and coagulopathy. There were 68 observations of the effects of colloidal solutions: 20% albumin solution (n=25), freshly frozen plasma (FFP) (n=20), 6% hydroxyethylated starch (HES) 130/0.4 9:1 (n=23). The colloidal solutions were infused at a constant rate; the infusion was stopped until pulmonary wedge pressure (PWP) was 25% greater than its baseline value. Before and after infusion, the parameters of central hemodynamics and oxygen transport, extravascular lung water index (ELWI), pulmonary vascular permeability index (PVPI), and colloid-osmotic pressure (COP) were measured. The infusion volumes were 3.8 +/- 0.4, 13.7 +/- 1.4, and 13.4 +/- 1.3 ml/kg for 20% albumin solution, 6% HES 130/0.4, and FFP, respectively. The PWP-COP gradient increased in all groups. After FFP infusion, there was an increase in ELWI and lung shunt. After 20% albumin solution, there was a delayed increase in ELWI. There was no rise in ELWI after 6% HES administration. In the 20% albumin solution group, the increased ELWI was recorded in patients who had positive baseline PWP-COP gradients (p < 0.05). A combination of higher PVPI and a positive PWP-COP value causes a greater increase in ELWI after 20% albumin solution infusion than in the normal PVPI group. In patients with ALPL, FFP infusion may lead to an increase in the accumulation of extravascular lung water. A negative preinfusion PWP-COP gradient is a safety criterion for the infusion of 20% albumin solution in patients with ALPL. The increased PVPI in combination with a positive PWP-COP gradient is an aggravating factor.

Acute Disease↗

Lowering the calcium concentration in St. Thomas' Hospital cardioplegic solution improves protection during hypothermic ischemia.

The concentration of calcium (1.2 mmol/L) in clinical St. Thomas' Hospital cardioplegic solution was chosen several years ago after dose-response studies in the normothermic isolated heart. However, recent studies with creatine phosphate in St. Thomas' Hospital solution demonstrated that additional myocardial protection during hypothermia resulted principally from its calcium-lowering effect in the solution. The isolated working rat heart model was therefore used to establish the optimal calcium concentration in St. Thomas' Hospital solution during lengthy hypothermic ischemia (20 degrees C, 300 minutes). The calcium content of standard St. Thomas' Hospital solution was varied from 0.0 to 1.5 mmol/L in eight treatment groups (n = 6 for each group). During ischemia, hearts were exposed to multidose cardioplegia (3 minutes every 30 minutes). Postischemic recovery of function was expressed as a percentage of preischemic control values. Release of creatine kinase and the time to return of sinus rhythm during the reperfusion period were also measured. These dose-response studies during hypothermic ischemia revealed a broad range of acceptable calcium concentrations (0.3 to 0.9 mmol/L), which appear optimal in St. Thomas' Hospital solution at 0.6 mmol/L. This concentration improved the postischemic recovery of aortic flow from 22.0% +/- 5.9% with control St. Thomas' Hospital solution (calcium concentration 1.2 mmol/L) to 86.0% +/- 4.0% (p less than 0.001). Other indices of functional recovery showed similar dramatic results. Creatine kinase release was reduced 84% (p less than 0.01) in the optimal calcium group. Postischemic reperfusion arrhythmias were diminished with the loser calcium concentration, with a significant decrease in the time between initial reperfusion until the return of sinus rhythm. In contrast, acalcemic St. Thomas' Hospital solution precipitated the calcium paradox with massive enzyme release and no functional recovery. Unlike prior published calcium dose-response studies at normothermia, these results demonstrate that the optimal calcium concentration during clinically relevant hypothermic ischemia is considerably lower than that of normal serum ionized calcium (1.2 mmol/L) and appears ideal at 0.6 mmol/L to realize even greater cardioprotective and antiarrhythmic effects with St. Thomas' Hospital solution.

Animals↗

Bar-code technology for documenting administration of large-volume intravenous solutions.

The failure to properly document dispensing, administration, charging, and crediting of large-volume plain i.v. solutions in a hospital, along with the potential for using bar-code technology to reduce documentation discrepancies, was investigated. Portable bar-code scanners and preprinted bar-code labels were employed to identify large-volume plain i.v. solutions administered on two selected nursing units of a 1000-bed, private, not-for-profit hospital. Inservice training sessions were conducted to instruct hospital personnel in the use of the scanning equipment. Comparisons of patient statements and medication administration records for large-volume plain i.v. solutions established the level of documentation errors in the study hospital. The causes of these errors were traced to three primary sources: (1) failure to document administration of a solution to a patient (38%), (2) failure to credit patients for i.v. solutions returned to the pharmacy (37%), and (3) administration of a solution to a patient other than the patient for whom the solution was dispensed (25%). Accountability for large-volume plain i.v. solution charges to patients was improved by 19% using bar-code technology. The pharmacy manager desiring to employ bar-code technology should determine convenient methods for applying bar-code labels to solutions and for scanning the bar codes, as well as provide programming that can compensate for erroneous scans.

Documentation↗

Compatibility of imipenem-cilastatin sodium with commonly used intravenous solutions.

The stability of imipenem-cilastatin sodium (Primaxin, Merck Sharp & Dohme) in various intravenous fluids was determined after storage at 4 degrees C or 25 degrees C and after freezing. Samples of imipenem-cilastatin sodium were constituted with 100 mL of each of 17 i.v. fluids to concentrations of 2.5 mg/mL or 5.0 mg/mL of each drug component and stored in glass infusion bottles at constant room temperature (25 degrees C) or constant refrigerated temperature (4 degrees C). The concentration of each solution was determined immediately after constitution by a stability-indicating high-performance liquid chromatographic assay; the concentrations of both drugs were monitored in each i.v. fluid until the time that the concentration of either imipenem or cilastatin decreased to less than 90% of the initial concentration (t90). The exact value of t90 was determined for each solution by linear regression. The solutions were also assessed for changes in pH or color. Cilastatin sodium was more stable in all 17 i.v. fluids than imipenem. The stability of imipenem was dependent on the concentration of that drug in solution; solutions of imipenem 2.5 mg/mL were more stable than solutions of imipenem 5.0 mg/mL. The values of t90 for imipenem in solutions stored at 4 degrees C were greater than the values for solutions stored at 25 degrees C. Imipenem was most stable in 0.9% sodium chloride injection. The pH values of the solutions generally decreased during the study period.(ABSTRACT TRUNCATED AT 250 WORDS)

Chromatography, High Pressure Liquid↗

Impairment of myocardial function induced by particulate contamination of cardioplegic solutions.

The U.S. Pharmacopoeia defines acceptable limits of particle contamination for intravenous solutions. Used conventionally, these solutions are filtered by the lungs, and there are few reports of particle-induced tissue injury to the systemic circulation. We have used an isolated rat heart model to assess whether unfiltered direct intraarterial administration of cardioplegic solutions, as in open-heart surgery, can be damaging to the myocardium. An intravenous solution of U.S. commercial manufacture was selected for evaluation. Particle-counting revealed this solution to be well within the U.S.P. limits. Direct intracoronary infusion of this solution at 20 degrees C and at constant pressure led to an approximate 75% reduction in coronary flow over 20 min. Filtration through a membrane of 0.8-micron porosity largely prevented this reduction of coronary flow. In studies with multidose cardioplegia (3-min infusions every 30 min), hearts given filtered solution recovered almost 90% of their preischemic functional capacity after 3 hr of hypothermic (20 degrees C) ischemic arrest. Hearts given an identical unfiltered solution essentially failed to recover despite the particle counts having conformed to the U.S.P. limit. This functional result was supported by measurement of creatine kinase leakage, which was significantly higher in the unfiltered group. These studies provide an argument for revision of U.S.P. particle limits when applied to intraarterially administered solutions; in particular, we believe that equipment for cardioplegic infusion into coronary arteries should incorporate a 0.8-micron in-line filter.

Animals↗

[What control solutions should be used in studies on the acute effect of alcohol on the gastrointestinal tract?].

There exists still a considerable confusion in the literature about the appropriate control solution for ethanol. In many studies either no control or equimolar solutions of urea, mannitol or sodium chloride were used as an osmotic control for ethanol; distilled water being given only in a few cases. The confusion is mainly derived from the opinion that the osmolality of the ethanol solution as measured by freezing point depression (= "theoretical osmotic pressure") is the determinant factor for the action of ethanol on the gastrointestinal tract. This opinion, however, is not correct. Since biological membranes are not perfectly semipermeable (i. e., they are permeable to certain solutes) the "effective osmotic pressure" produced by permeant solutes is always less than the ("theoretical") osmotic pressure as determined by freezing point depression. The ratio of the "effective" to the "theoretical" osmotic pressure of a solute is defined by the Stavermann reflection coefficient for a certain membrane. The Stavermann reflection coefficient may have any value between 1 and 0. For an impermeant solute the reflection coefficient equals 1 and for increasingly permeant solutes it becomes progressively less than 1 and closer to 0. The Stavermann reflection coefficient of ethanol for some gastrointestinal organs tested is about 0.1. The ideal osmotic control for ethanol would be a solute which exerts the same effective osmotic pressure on the gastrointestinal membrane as ethanol, i. e. which has the same Stavermann reflection coefficient as ethanol, and has no specific pharmacologic effect. Distilled water seems to be the most suitable osmotic control for ethanol because it has a Stavermann reflection coefficient of 0 and has no pharmacological actions.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Stability of amino acids and the availability of acid in total parenteral nutrition solutions containing hydrochloric acid.

The stability of amino acids and the availability of acid from total parenteral nutrition (TPN) solutions containing hydrochloric acid were studied. Hydrochloric acid in the concentrations of 40 (TPN 1), 60 (TPN 2), and 100 (TPN 3) meq/liter was added to TPN solutions (4.25% amino acids, 25% dextrose monohydrate) containing various electrolytes (TPN control). Amino acid concentrations were determined from one sample of each solution using a Technicon Automatic Amino Acid Analyzer. Samples were analyzed 24 hours after mixing and compared with the TPN control at 24 hours. Tryptophan was assayed using a specific colorimetric assay at 0, 6, 24, and 48 hours. The concentrations of proline (76.2 of control) and histidine (85.7% of control) wee decreased in TPN 3. This phenomenon appeared to be dependent upon the concentration of hydrochloric acid in the TPN solution. There was no appreciable loss of any of the other amino acids in the test solution as compared with the control. Tryptophan levels fell in both the TPN control and the test solutions independent of the hydrochloric acid concentration. The pH of the solutions decreased with increasing concentrations of hydrochloric acid from 5.87 in the TPN control to 3.18 in TPN 3. The titratable acidity increased with increasing concentrations of hydrochloric acid (28.21 meq/liter in the TPN control to 115.54 meq/liter in TPN 3). Concentrations of some amino acids decreased in the presence of hydrochloric acid. Because of the short-time period in which these solutions will usually be infused (4-24 hours), this probably has a negligible effect on patients' nutritional therapy. The availability of acid from these solutions makes this combination useful in treating severe metabolic alkalosis.

Alkalosis↗

Calcium and phosphorus compatibility in parental nutrition solutions for neonates.

Factors affecting calcium-phosphate solubility in parenteral nutrition solutions used in neonates were studied. Six neonatal parenteral nutrition solutions were prepared using either Aminosyn or FreAmine III and various amino acid and dextrose concentrations. Phosphorus (as mono- and dibasic potassium phosphate) and calcium (as 10% calcium gluconate) were added in concentrations of calcium 2.5-100 meq/liter and phosphorus 2.5-100 mmol/liter. Duplicate samples were prepared and analyzed either after they were heated in a water bath (37 degrees C) for 20 minutes or after 18 hours at 25 degrees C followed by 30 minutes in a water bath (37 degrees C). Precipitation was detected visually and spectrophotometrically, and pH was measured. Lipid emulsion was added to two Fre-Amine III solutions in a ratio of 7.5:1 (parenteral nutrition solution:lipid) and the resulting pH was measured. Time and temperature affected calcium-phosphate solubility in all solutions tested. Precipitation curves of amount of calcium versus amount of phosphate added were prepared for each solution. Amino acid and dextrose concentrations affected the pH of the solutions, and when a lipid emulsion was added, the pH rose more in the 1% than in the 2% FreAmine III solution. In selected solutions, as much as 120 mg/kg/day calcium and 55 mg/kg/day phosphate can be administered, approximating daily third-trimester accumulation of these minerals. Use of the precipitation curves in this paper, with attention to their limitations, should aid in the safe delivery of calcium and phosphorus intravenously to neonates.

Amino Acids↗

Diluting lidocaine and mepivacaine in balanced salt solution reduces the pain of intradermal injection.

BACKGROUND AND OBJECTIVES: Intradermal injection of local anesthetics prior to percutaneous needle insertion is often painful. This study evaluated the effect of diluting lidocaine and mepivacaine with balanced salt solution on perception of pain on intradermal injection. METHODS: Twenty healthy volunteers were each intradermally injected with six solutions in random order. These solutions were: normal saline (NS), 0.9% benzyl alcohol in NS, 0.2% lidocaine in NS, 0.2% lidocaine in balanced salt solution, 0.2% mepivacaine in NS, and 0.2% mepivacaine in balanced salt solution. Discomfort of each injection was reported on a 0-2 pain scale. The degree of anesthesia at each site was evaluated by pinprick every minute for 20 minutes. RESULTS: Benzyl alcohol and lidocaine and mepivacaine in balanced salt solution caused the least injection pain. However, mepivacaine in NS and NS alone caused the most pain. The anesthetic effect of benzyl alcohol was judged adequate for only 4 minutes whereas both lidocaine and mepivacaine in either NS or balanced salt solution gave adequate anesthesia for at least 15 minutes. CONCLUSIONS: The dilution of lidocaine and mepivacaine with balanced salt solution produces a solution that is both painless on injection and of moderate duration.

Adult↗

Dialysate to plasma solute concentration (D/P) versus peritoneal transport parameters in CAPD.

The relationship between dialysate to plasma solute equilibration ratio (D/P) and diffusive (diffusive mass transport coefficients, KBD) as well as convective (sieving coefficient, S, and net ultrafiltration) transport characteristics were studied in clinically stable CAPD patients and in patients with loss of ultrafiltration capacity (UFC). Forty-one 6-h single-dwell studies with standard glucose-based dialysis fluids containing 1.36% (n = 9), 2.27% (n = 9), and 3.86% (n = 23) anhydrous glucose were carried out in 33 clinically stable CAPD patients. Eleven patients with loss of UFC were studied with 3.86% glucose solution. Intraperitoneal dialysate volumes were calculated from the dilution of the tracer (131I-albumin) with a correction applied for its elimination from the peritoneal cavity. KBD and S were estimated using the Pyle-Popovich-Moncrief model with aqueous plasma concentrations. A theoretical D/P curve was derived with and without taking convective transport and peritoneal reabsorption into account. The three different glucose solutions yielded D/P curves which were similar for urea and potassium. For creatinine a slower equilibration and for glucose and sodium a faster decrease in dialysate concentration were observed with more hypertonic solutions. In general, there was a strong correlation which was best at 240 min between D/P (for glucose dialysate/initial dialysate concentration, D/Do) and KBD for all solutes (except sodium), whereas the correlation between D/P and convective transport parameters was much weaker. KBD for creatinine (with 3.86% glucose solution) could be estimated (r = 0.98) from aqueous D/P using the experimental formula: creatinine KBD = -1.8 - ln (1 - D240/P)/0.1. Patients with loss of UFC due to increased diffusive transport (n = 8) could be discriminated from the clinically stable patients using KBD and D/P (or D/D0) for creatinine and glucose or D/P for sodium. However, patients with loss of UFC associated with increased peritoneal reabsorption (n = 2) could not be identified using these parameters. Theoretically derived D/P curves were in excellent agreement with measured D/P for 1.36% glucose solution and simulations were satisfactory also for the 2.27% and 3.86% solutions provided that the effect of convective transport was taken into account. The standardized peritoneal equilibration tests (PET) as proposed by Twardowski et al. [17] seems to be appropriately designed as regards duration of the dwell and the choice of glucose and creatinine as investigated solutes. Thus, PET can be recommended as a sensitive routine investigation for the monitoring of normal/abnormal peritoneal transport behaviour in peritoneal dialysis patients.

Biological Transport↗

Prevention of postoperative pericardial adhesions with a hyaluronic acid coating solution. Experimental safety and efficacy studies.

Postoperative pericardial adhesions complicate reoperative cardiac procedures. Topical application of solutions containing hyaluronic acid have been shown to reduce adhesions after abdominal and orthopedic surgery. The mechanism by which hyaluronic acid solutions prevent adhesion formation is unknown but may be due to a cytoprotective effect on mesothelial surfaces, which would limit intraoperative injury. In this study, we tested the efficacy and safety of hyaluronic acid coating solutions for the prevention of postoperative intrapericardial adhesion formation. Eighteen mongrel dogs underwent median sternotomy and pericardiotomy followed by a standardized 2-hour protocol of forced warm air desiccation and abrasion of the pericardial and epicardial surfaces. Group 1 (n = 6) served as untreated control animals. Group 2 (n = 6) received topical administration of 0.4% hyaluronic acid in phosphate-buffered saline solution at the time of pericardiotomy, at 20-minute intervals during the desiccation/abrasion protocol, and at pericardial closure. The total test dose was less than 1% of the circulating blood volume. Group 3 (n = 6) served as a vehicle control, receiving phosphate-buffered saline solution as a topical agent in a fashion identical to that used in group 2. At resternotomy 8 weeks after the initial operation, the intrapericardial adhesions were graded on a 0 to 4 severity scale at seven different areas covering the ventricular, atrial, and great vessel surfaces. In both the untreated control (group 1, mean score 3.2 +/- 0.4) and vehicle control (group 3, mean score 3.3 +/- 0.2) animals, dense adhesions were encountered. In contrast, animals treated with the hyaluronic acid solution (group 2, mean score 0.8 +/- 0.3) characteristically had no adhesions or filmy, transparent adhesions graded significantly less severe than either the untreated control (group 2 versus group 1, p < 0.001) or vehicle control (group 2 versus group 3, p < 0.001) animals. In separate experiments, six baboons were infused with 0.4% hyaluronic acid in phosphate-buffered saline solution in volumes equivalent to 2.5%, 5%, and 10% of the measured circulating blood volume. The 2.5% and 5% infusions had no effect on the parameters measured; infusion of the 10% volume produced transient hemodynamic, coagulation, and gas exchange abnormalities. Hyaluronic acid solutions are efficacious in the prevention of pericardial adhesions in this model, and they appear safe in doses five times the amount needed to prevent adhesions. Further studies investigating the mechanism by which these solutions prevent adhesions, their optimal dose and method of application, and documentation of their safe use in humans are warranted.

Animals↗

[Effectiveness of peroxide solutions against microorganisms in biofilms].

Central dosing units for surface disinfectants can constitute a particular hygiene problem in hospitals if a biofilm can develop in the piping system despite the disinfectant solution that is present. In earlier studies it was able to be shown that oxygen-releasing compounds in particular were highly effective against microorganisms in generated biofilms. The purpose of the study presented was to investigate in a test simulating practical conditions whether, in addition to the described good effect, peroxide-containing solutions also have a uniform effect against all isolates from disinfectant use-solutions, or whether there are differences. The results show that a 1% H2O2 solution (C) was not sufficiently effective against all test organisms after a contact time of one hour. In contrast, the 1% test solution of A (10% perglutaric acid, 28% H2O2, < 0.5% perbenzoic acid) was highly and uniformly effective. The 3% test solution of B (10% tertiary butylhydroperoxide, 20% phenoxypropanols, 48% dipropylene glycol) exhibited weaknesses against some test organisms after the one-hour contact time. After a contact time of three hours, this solution, unlike the 1% H2O2 solution achieved a reduction in bacterial count of more than 5 log steps against all species. On the basis of these results, before cleaning piping systems it appears advisable to test the effectiveness of the solution to be used in a suitable test with the isolates.

Animals↗

The impact of liver preservation in HTK and UW solution on microcirculation after liver transplantation.

Severe microcirculatory disturbances due to endothelial cell damage and leukocyte adherence during reperfusion of transplanted livers are considered to contribute to early graft failure. Since the degree of reperfusion injury after liver transplantation depends on the length of preservation time and the solution used for preservation, the aim of our study was to assess three solutions with respect to microvascular perfusion and leukocyte adhesion. Therefore, rat livers were stored up to 24 h in Euro-Collins (EC), University of Wisconsin (UW), or histidin-tryphtophan-ketoglutarate (HTK) solutions prior to orthotopic transplantation. The livers were studied in situ 60 min postoperatively using intravital fluorescence video microscopy. Using simple syringe flushing (10 ml), sinusoidal perfusion decreased below 50% in EC preserved livers after 8 h preservation, in HTK preserved livers after 16 h preservation, and remained higher than 70% in livers preserved in UW up to 24 h. Permanent adhesion of leukocytes was increased more rapidly in organs after 1, 8, 16, and 24 h preservation in HTK (16%, 15%, 34%, and 49.7% +/- 4.7%) compared to those preserved in UW (15%, 18%, 17%; and 32.7% +/- 3.3%; P<0.05). Using a 10-fold volumn of the organ weight of HTK solution during the harvesting procedure, with an 8 min equilibration period, sinusoidal perfusion (39.6 +/- 4.7%) and leukocyte adhesion (42.7 +/- 3.1%) were not improved after 24 h. In contrast, equilibration with a volumn of approximately 40-times the liver weight improved sinusoidal perfusion (70.8% +/- 2.7%; P < 0.01) and leukocyte adhesion (24.9% +/- 3.1%; P < 0.01) significantly. Thus, using HTK solution, simple flushing prior to long-term cold storage resulted in microcirculatory disturbances when compared to UW solution. Larger volumns of HTK solution with an additional equilibration period of 8 min, however, reduced leukocyte adhesion and improved sinusoidal perfusion to a similar degree as UW solution.

Adenosine↗

Minimal amounts of hyaluronidase in HTK or UW solution substantially improve the recovery of preserved hearts.

Rat hearts were preserved by simple storage for 18 h at 0-1 degree C and reperfused parabiotically with whole blood from a host rat. The preservation solutions used for flush perfusion and storage were the commercial solutions EuroCollins, HTK, or UW with or without adding 40 mg/l hyaluronidase or EuroFlush-Glutathione (EFG) solution, especially designed for prolonged heart storage. All solutions were filtered (0.45 micron) before use. The functional recovery was measured using a latex balloon in the left ventricle for LVP, dp/dt, and isotonic stroke volume. The metabolic recovery as well as the edema formation was determined from freeze-clamped myocardium at the end of reperfusion. In hearts preserved with hyaluronidase-containing solutions, the edema formation during reperfusion was reduced combined with an improvement in the coronary flow. Functional and metabolic recovery were improved in these hearts with significant increase in the stroke volume and ECP in all groups versus hearts preserved in the hyaluronidase-free basic solutions. The effectiveness of HTK preservation was significantly improved by hyaluronidase in all parameters measured in our study. The best functional and metabolic recovery was found in hearts preserved by HTK + H- or EFG-solution. Thus, preservation solutions containing hyaluronidase, especially HTK + H and EFG, seem best suited for the prolonged storage preservation of the heart.

Adenosine↗

Effect of different preservation solutions on adenine nucleotide content and metabolism in human kidney transplantation.

Differences in purine metabolism produced by three preservation solutions were studied by determining the adenine nucleotide (ATP, ADP, AMP, and IMP) and nucleoside (adenosine, inosine, and hypoxanthine) levels in human kidney cortical biopsies. Forty kidney allografts were studied using University of Wisconsin (UW) solution (n = 20), Euro-Collins (EC) solution (n = 12), and modified EC solution with mannitol (M; n = 8). No significant differences were found between the three solutions studied with regard to ATP, ADP, or AMP changes. The mean ATP level (nmol/mg prot +/- SEM) at the end of preservation in the UW group was 2.7 +/- 0.3 nmol/mg, in the EC group 3.8 +/- 0.7 nmol/mg, and in the M group 2.3 +/- 0.4 nmol/mg. ATP 30 min after reperfusion in the UW, EC, and M groups was 5.7 +/- 0.8 nmol/mg, 6.4 +/- 1.0 nmol/mg, and 4.6 +/- 0.5 nmol/mg, respectively. However, an important difference appeared in the catabolic products determined. Kidneys perfused with UW solution had a significantly higher level of adenosine (2.6 +/- 0.6 nmol/mg), inosine (11.8 +/- 2.2 nmol/mg), and hypoxanthine (18.1 +/- 2.1 nmol/mg) at the end of cold storage than those perfused with EC (0.4 +/- 0.1 nmol/mg, 2.0 +/- 0.8 nmol/mg, and 7.1 +/- 1.4 nmol/mg) and M solutions (0.2 +/- 0.05 nmol/mg, 0.5 +/- 0.1 nmol/mg, and 5.2 +/- 0.6 nmol/mg; P < 0.05). These levels returned to initial values 30 min postreperfusion and there were no differences with the EC or M solution groups at that time.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenine Nucleotides↗

A novel dextran 40-based preservation solution.

Although the University of Wisconsin (UW) solution has become the standard solution for the preservation of kidneys for transplantation, the importance of the colloid hydroxyethylstarch (HES), one of the key compounds of the UW solution, has been questioned repeatedly. It is now established that HES is not necessary for routine kidney preservation. However, colloids may still be advantageous in UW like solutions for the purpose of multiorgan procurements and the preservation of organs from marginal donors. It has been shown in various experimental models that dextran 40 may successfully substitute for HES. Dextran 40 is not only cheaper but also has a variety of biological effects that may be beneficial during the graft reperfusion phase. The aim of this clinical study was to examine the efficacy of a dextran 40-based preservation solution (Dex-PS) for its use in human kidney graft preservation and to compare the transplantation results with kidneys preserved with UW solution. A total of 87 kidneys were preserved with Dex-PS and matched with 87 kidneys preserved with UW solution. Both groups were comparable in terms of donor and recipient characteristics and both had a high proportion of kidneys from nonheart-beating donors. Patient survival and graft survival after 1 year were 95% and 86% for the Dex-PS group and 94% and 90% for the UW group, respectively (P = NS). Primary nonfunction, delayed graft function, postoperative need for dialysis, and follow-up of serum creatinine were statistically comparable between these two groups. We conclude that dextran 40 can safely replace HES in UW solution for the purpose of clinical kidney preservation. There were no statistically detectable differences in graft performance between the kidneys preserved with UW and those preserved with Dex-PS.

Adenosine↗