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Head injury and hemorrhagic shock: studies of the blood brain barrier and intracranial pressure after resuscitation with normal saline solution, 3% saline solution, and dextran-40.

The effect of fluid resuscitation from hemorrhagic shock on cerebral edema, intracranial pressure (ICP), and blood brain barrier function was investigated in the presence of a simulated head injury. Beagle dogs were anesthetized and ICP was measured via a right subarachnoid bolt while a contralateral epidural balloon was inflated in the left hemicranium to mimic a closed head injury. Forty percent of the dogs' blood was shed and the shock state was maintained for 1 hour. Resuscitation was initiated with shed blood and a volume of either normal saline solution (NS, n = 5), 10% dextran-40 (D-40, n = 6), or hypertonic (3%) saline solution (HS, n = 6) equal to the amount of shed blood. Evans blue solution was infused intravenously, and intravascular volume was then maintained with normal saline solution. Control (n = 5) dogs did not undergo shock, but received equivalent volumes of normal saline solution and Evans blue solution. The dogs were killed after 2 hours of resuscitation, and the brains were removed, weighed, and fixed in formalin. The average intracranial pressure value after epidural balloon inflation was 18.6 +/- 0.80 mm Hg and decreased equally in all groups during the shock period, averaging 10.8 +/- 1.24 mm Hg at the end of the shock period. Fluid resuscitation markedly elevated ICP in the NS and D-40 groups, reaching maximal values of 46.6 +/- 12.11 mm Hg and 45.3 +/- 28.95 mm Hg, respectively. Maximal ICP values in control and HS groups measured 21.8 +/- 1.36 mm Hg and 15.8 +/- 2.04 mm Hg, respectively (p less than 0.25 for HS versus NS control). Wet brain weights were significantly less in the HS group compared with either NS or D-40 groups (p less than 0.05). Coronal sections of fixed HS brains showed deep cortical Evans blue staining on the side of balloon injury. Therefore, in the presence of an intracranial mass lesion, resuscitation with hypertonic (3%) saline solution is accompanied by lower ICP values and less cerebral edema than is isotonic saline or colloid resuscitation. Blood brain barrier function is not restored by hypertonic saline solution resuscitation.

Animals↗

Comparison of saphenous vein graft relaxation between Plasma-Lyte solution and normal saline solution.

Venospasm of saphenous vein grafts may damage endothelial cells and compromise early and late graft performance. Hence it is desirable to identify and use storage solutions that minimize vascular spasm during vein preparation. In view of this, we initiated isometric tension-recording studies in isolated canine and human saphenous vein to evaluate the acute, vasoactive effects of two storage solutions, Plasma-Lyte solution and normal saline solution. In initial experiments, canine saphenous veins were mounted in tissue baths containing physiologic salt solution and tonically constricted by 2 x 10(-6) mol/L norepinephrine. The physiologic salt solution in the bath was then replaced by Plasma-Lyte solution or normal saline solution containing the same norepinephrine concentration, and changes in contraction amplitude were recorded for 90 minutes. Storage in Plasma-Lyte solution at 37 degrees C completely relaxed norepinephrine-activated canine saphenous vein within 20 minutes, whereas veins remained partially constricted in normal saline solution. Both Plasma-Lyte solution and normal saline solution relaxed canine saphenous vein less at room temperature (25 degrees C) than at 37 degrees C, implying that warming of storage solutions in the operating room may promote graft dilation. To identify the mechanism by which Plasma-Lyte solution induced relaxation, we replaced its putative vasodilator components of gluconate and acetate with NaCl, but this alteration did not reduce relaxation induced by Plasma-Lyte solution. However, adding 1.6 mmol/L CaCl2 to Plasma-Lyte solution completely reversed the venodilation, suggesting that the low Ca2+ content of Plasma-Lyte solution confers its relaxant action. Finally, we tested the vasoactive effect of Plasma-Lyte solution on human saphenous vein obtained by discard from coronary bypass operations. Plasma-Lyte solution at 37 degrees C effectively dilated norepinephrine-activated human saphenous vein, inducing complete relaxation within 20 minutes. On this basis, we recommend the use of Plasma-Lyte solution as a venodilating storage solution during coronary bypass operations to optimize vein graft relaxation before implantation.

Acetates↗

Influence of preinduction methoxamine, lactated Ringer solution, or hypertonic saline solution infusion or postinduction dobutamine infusion on anesthetic-induced hypotension in horses.

A controlled study of the cardiovascular responses in horses anesthetized with acepromazine (0.05 mg/kg of body weight, IV), guaifenesin (100 mg/kg, IV), thiamylal (5.0 mg/kg, IV), and halothane in O2 (1.2 to 1.4% end-expired concentration) was performed to determine whether hypotension could be prevented by use of various treatments. Six horses were given 5 treatments in a randomized sequence: no treatment (control), methoxamine (0.04 mg/kg, IV), lactated Ringer solution (20.0 ml/kg, IV), 7.5% hypertonic saline solution (4.0 ml/kg, IV), or constant infusion of dobutamine (5.0 mg/kg/min, IV) during anesthesia. Heart rate, ECG, blood pressure, central venous pressure, cardiac output, blood gas analysis, PVC, and plasma total protein concentration were measured during the study. Compared with the control value, an increase in blood pressure during halothane administration was observed after administration of lactated Ringer solution, hypertonic saline solution, or dobutamine (P less than 0.05). The improved blood pressure response to hypertonic saline solution and dobutamine was related to an increase in cardiac output, which was statistically significant (P less than 0.05). Other statistically significant differences in cardiopulmonary responses among treatments were not observed during anesthesia. The PCV was increased in response to dobutamine infusion, and plasma total protein concentration was reduced in response to administration of hypertonic saline or lactated Ringer solution.

Acepromazine↗

Effect of irrigation solutions for arthroscopic surgery on intraarticular tissue: comparison in human meniscus-derived primary cell culture between lactate Ringer's solution and saline solution.

In order to determine whether there is a difference in effect on cell morphology and function between two common arthroscopic irrigation solutions, primary cultures of cells derived from the surgically excised human menisci were incubated for 3 or 6 h in lactated Ringer's solution, isotonic sodium chloride solution, or serum-free cell culture medium (negative-control condition). Cell integrity was blindly evaluated by three independent examiners scoring photomicrographs of the cell cultures on a battery of five-point scales for abnormality of cell shape, irregularity of cell membrane, change of cell size and cell density. Cell cultures were also quantitatively assayed by semi-quantitative reverse-transcription-polymerase-chain-reaction for mRNA of alpha1 (I) procollagen, alpha1 (II) procollagen, aggrecan and heat-shock protein 70 to assess functional consequences of exposure to the solutions. There was a statistically significant difference in cell integrity scores between either lactated Ringer's solution or serum-free cell-culture medium and isotonic sodium chloride solution with greater damage to cells displayed. Scores for lactated Ringer's solution did not differ from those for serum-free cell-culture medium. There were no significant differences in mRNA expression level among the treatment conditions. It was concluded that the lactated Ringer's solution better maintained human meniscus cell integrity than the isotonic saline.

Adolescent↗

Are lactated Ringer's solution and normal saline solution equal with regard to coagulation?

UNLABELLED: Crystalloids represent an attractive strategy to alleviate intravascular volume deficits. Crystalloid hemodilution was associated with hypercoagulability in in vitro and in vivo studies. The influence of different crystalloids on coagulation in the surgical patient is not well studied. In a prospective, randomized study in patients undergoing major abdominal surgery, we used either lactated Ringer's solution (RL) (n = 21) or 0.9% saline solution (SS) (n = 21) exclusively for intravascular volume replacement over 48 h to maintain central venous pressure between 8 and 12 mm Hg. Activated thrombelastography (TEG) using different activators (intrinsic TEG, extrinsic TEG, heparinase TEG, aprotinin TEG) was used to measure coagulation time, clot formation time, and maximum clot firmness. Measurements were performed after induction of anesthesia (T0), immediately after surgery (T1), 5 h after surgery (T2), and on the morning of the first (T3) and second (T4) postoperative days. RL 18,750 +/- 1890 mL and 17,990 +/- 1790 mL of SS were infused during the study period. Acidosis was seen only in the SS-treated group. Blood loss was not different between the groups. Fibrinogen and antithrombin III decreased similarly at T1 and T2 in both groups, most likely because of hemodilution. Differences in TEG data from normal baseline were seen only immediately after surgery and 5 h thereafter, indicating mild hypercoagulability in the intrinsic TEG (RL, from 147 +/- 130 s to 130 +/- 11 s; SS, from 146 +/- 12 s to 131 +/- 12 s). There were no differences in coagulation between RL- and SS-treated patients. We conclude that in major abdominal surgery intravascular volume replacement with crystalloids resulted in only moderate and abbreviated changes in coagulation. No differences in activated TEG and blood loss were seen between an RL- and an SS-based intravascular volume replacement regimen. IMPLICATIONS: In 42 patients undergoing major abdominal surgery, either lactated Ringer's solution or 0.9% saline solution were exclusively used for volume therapy for 48 h. Activated thrombelastography revealed some mild hypercoagulability after surgery. No differences in coagulation were seen between the two intravascular volume replacement strategies.

Abdomen↗

Ringer-Lactate solution versus isotonic saline solution on mucociliary function after nasal septal surgery.

Irrigation with isotonic saline is one of the most frequently used solutions after nasal surgery. However, the effect of saline solutions on mucociliary clearance is not well known. In a previous study, it was found that isotonic saline solution had a negative effect on ciliary beat frequency but Ringer-Locke solution had no effect in vitro. In this study we compared the effects of Ringer-Lactate solution and isotonic saline solution on mucociliary transport time before, and after, nasal septal surgery in patients with nasal septal deviation. We found that patients who used Ringer-Lactate solution as irrigation after surgery had a significantly better mucociliary transport time than the patients using isotonic saline solution (p < 0.05). In conclusion, it is better to use Ringer-Lactate solution instead of 0.9 per cent saline solution for nasal irrigation.

Adolescent↗

Treatment of uncontrolled hemorrhagic shock with hypertonic saline solution.

Hypertonic saline solution (HTS) treatment of uncontrolled hemorrhagic shock (UCHS) induced by incision of three major branches of the ileocolic artery, leading to free intra-abdominal bleeding, was studied in rats. The rats were divided into two groups. In group 1, the abdominal wall was closed immediately after induction of hemorrhage and the rats were divided into six subgroups--1a, five untreated; 1b, 14 treated with 5 milliliters per kilogram of sodium chloride 7.5 per cent (HTS) after five minutes; 1c, eight had HTS infused after 15 minutes; 1d, nine had HTS infused after 30 minutes; 1e, nine had HTS infused after 60 minutes, and 1f, nine had HTS infused after 120 minutes. In rats in group 2, the abdominal wall was kept open during HTS therapy and bleeding was estimated by the amount of sponges used to absorb shed blood. These rats were also divided into six subgroups--2a, five untreated; 2b, nine had HTS infused after five minutes; 2c, six had HTS infused after 15 minutes; 2d, six had HTS infused after 30 minutes; 2e, eight had HTS infused after 60 minutes, and 2f, six had HTS infused after 120 minutes. UCHS in group 1 was followed by a fall in the mean arterial pressure (MAP) from 99 to 46 torr (p less than 0.001) in five minutes and a gradual rise to 63 torr (p less than 0.01) after 30 minutes, with a survival rate of 80 per cent. HTS infusion five minutes after hemorrhage was followed by a further fall in MAP to 37 torr (p less than 0.01) after 30 minutes and a mortality rate of 85.7 per cent (p less than 0.01). HTS treatment after 15, 30, 60 and 120 minutes also led to a further fall in MAP and increased mortality. In group 2, the hemodynamic response to intra-abdominal vessel injury in untreated rats was similar to that of those in group 1 and the amount of sponges used to absorb shed blood was 2.4. After five, 60 and 120 minutes of HTS treatment, the hemodynamic response was similar to that in group 1. Five and one-half (p less than 0.01), 3.5 and 3.0 sponges, respectively, were used to absorb shed blood.(ABSTRACT TRUNCATED AT 400 WORDS)

Abdominal Muscles↗

[Individualized hemodilution in acute brain infarct using a 20% albumin solution and physiological saline solution].

OBJECTIVE: To determine the effect of normovolaemic haemodilution in patients after a cerebrovascular accident. DESIGN: Prospective, randomized clinical trial. SETTING: St Lucas Hospital, Amsterdam. METHOD: Normovolaemic haemodilution was achieved by means of bloodletting and administration of a 20% solution of albumin plus crystalline infusion fluids under haemodynamic and rheological monitoring during the acute phase of the cerebral infarction. All patients were subjected to general intensive care and monitoring with a pulmonary artery catheter. This custom-tailored fluid therapy was guided by a pulmonary wedge pressure of 12 mm Hg (SD 3) and a haematocrit (Ht) of 0.32 l/l (SD 0.02). The control group only received individually dosed rehydration with crystalline infusion fluids. Endpoints of the study after 3 months were mortality and dependence/independence concerning everyday functioning. RESULTS: The results in the total haemodilution group and the control group did not differ significantly. However, in the subgroup with normal Ht (< 0.45 l/l; n = 201) there was a significant reduction (p < 0.05) of the mortality after 3 months (27% and 16%, respectively) and an increase of independence at home (35% and 48%, respectively) due to a reduction of the viscosity by means of haemodilution with albumin (a specific viscosity effect in the normovolaemic group). In the control group with raised Ht (dehydration; Ht > or = 0.45 l/l; n = 50) there was a significant decrease (p < 0.005) of the mortality after 3 months (27% and 8%, respectively) and an increase of independence at home (35% and 59%, respectively) compared with the control group with normal Ht without signs of dehydration (Ht < 0.045 l/l; n = 102), due to rehydration exclusively with crystalline infusion fluids (a specific rehydration effect in the dehydrated group). CONCLUSION: In cerebrovascular accident patients haemodilution should be adjusted individually; in normovolaemic patients haemodilution should be carried out with an albumin solution; the higher the Ht, the more rehydration with crystalline infusion fluids is to be carried out.

Activities of Daily Living↗

[Comparison of temperature increments in bone cavities induced by methylmethacrylate and heated saline solution].

OBJECTIVES: We administered saline solution at 70 degrees C and methylmethacrylate to varying volumes of bone cavities and compared temperature changes produced in bone regions at varying distances to the cavity wall. METHODS: We created varying sizes of cavities in the femoral heads of 20 human cadavers (6, 10, 12, and 20 cubic centimeters) and in the knee region of a human cadaver (6, 10, 12, 20, 30, and 40 cubic centimeters). Initially, saline solution at 70 degrees C was administered to all the cavities for 15 minutes by a pulse-irrigation method, during which temperature changes induced within the bone cavity and at specific distances (1, 2, 3, and 10 mm) to the cavity wall were recorded. The bone temperatures were allowed to return to initial values; thereafter, cement was applied and temperature changes at the same distances to the cavity wall, in the cement center, and on the cement surface were recorded. RESULTS: Cement volumes up to 40 cubic centimeters applied to the bone cavities did not produce temperature increments that are reported to be adequate to induce necrosis in the cavity wall. It was thought that cement-induced necrosis in the bone-cement interface was not related to heat, but to other effects exerted by cement application. Compared to cement-induced temperature changes, saline solution at 70 degrees C was always associated with higher temperature increments in the cavity wall. CONCLUSION: Due to its simple applicability at desired temperatures and for any lengths of time, heated saline solution seems to have credentials to be incorporated into local adjuvants that are utilized to eliminate tumoral contamination in the cavity wall following curettage for local aggressive tumors.

Arthroplasty↗

[Hypertonic saline solutions in resuscitation in hemorrhagic shock. An experimental study].

The aim of the study was to evaluate the use of hypertonic solutions in restoring intravascular volume in a model of hemorrhagic shock. Eighteen pigs underwent general anesthesia and were instrumented with a carotid catheter to record mean arterial pressure (MAP), a pulmonary artery catheter for pulmonary arterial pressure (MPAP) and cardiac output (CO) monitoring and an electromagnetic flowmeter around the abdominal supraceliac aorta for aortic flow measurement (Vaor). Oxygen delivery (DO2) and oxygen consumption (VO2) data were calculated by standard formulas. The animals were hemorrhaged to a MAP of 45 mmHg, held for 1 hour. They were resuscitated during the following hour until the aortic flow regained its basal value, using three different solutions: normotonic saline (NS = NaCl 0.9%), hypertonic saline (HS = NaCl 7.5%), hypertonic saline added with dextran (HSDX = NaCl 7.5% + 6% dextran 70). An hour of autologous blood transfusion and a two hours follow-up concluded the experiment. Volumes infused were remarkably lower administering HS (13.70 +/- 1.44 ml/kg) and HSDX (9.11 +/- 1.20 ml/kg) compared to NS (90.32 +/- 24.83 ml/kg). MAP, CO and DO2 values resulted significantly higher in the HSDX animals, with lower MPAP levels. During the two hours follow-up only the animals reinfused with HSDX maintained hemodynamic and oxygen transport values at normal levels. We conclude that the administration of hypertonic saline solutions during hemorrhagic shock allows the saving of infusion volumes, thus diminishing the occurrence of interstitial edema formation. The adding of dextran to the solution prolongs the hemodynamic effects.

Animals↗

Use of exhaled breath condensate in the study of airway inflammation after hypertonic saline solution challenge.

STUDY OBJECTIVES: Hypertonic saline solution inhalation is suspected to produce airway inflammation. DESIGN: The aim of this study was to verify this hypothesis by measuring inflammatory markers in exhaled breath condensate (EBC) collected before and after sputum induction with hypertonic and isotonic saline solution. PATIENTS AND METHODS: We enrolled 10 patients with asthma, 10 patients with COPD, and 7 healthy subjects with no history of lung disease. Levels of interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha were measured in EBC by a specific enzyme immunoassay kit. Exhaled pH was measured after deaeration/decarbonation by bubbling with argon (350 mL/min) for 10 min by means of a pH meter. MEASUREMENTS AND RESULTS: Exhaled IL-6 and TNF-alpha concentrations were greater and pH was decreased compared to baseline after hypertonic saline solution inhalation in each group of subjects studied. No changes were observed following isotonic saline solution inhalation. Concentrations of IL-6, TNF-alpha, and pH in EBC correlated. CONCLUSIONS: These findings suggest that hypertonic saline solution inhalation could cause a low-grade inflammation in airways, and levels of inflammatory markers such as IL-6, TNF-alpha, and pH in EBC may be a useful noninvasive way to assess and monitor airway inflammation.

Aged↗

Influence of hypertonic saline solution infusion on defibrillation efficacy.

Hypertonic saline solution may enhance cardiac conduction via the fast inward sodium channel and alter transmembrane Ca+2 conductance via the sodium-calcium exchanger. Evidence suggests that both Ca+2 conductance and myocardial conduction velocity may affect ventricular defibrillation. Since hypertonic saline solution solutions (ie, sodium bicarbonate) may be administered to patients who have conditions that often require ventricular defibrillation (ie, cardiac arrest or hypovolemic shock), we studied the effect of hypertonic saline solution on the defibrillation threshold (DFT) in 16 pentobarbital-anesthetized domestic farm swine (20 to 30 kg). Defibrillation was performed using two interfaced epicardial electrode patches. DFTs were determined at baseline and during treatment phase. Pigs were randomly assigned to treatment consisting of either hypertonic saline solution (6 mmol/kg load, 2.0 to 3.0 mmol/kg infusion) to maintain serum sodium concentrations 10 to 15 mmol/L above baseline or control (D5W given in equal volume). DFT values (joules) that predicted 50% success were modeled from a best-fit histogram. Hypertonic saline solution did not change DFT values from baseline values (10.2 +/- 4.3 vs 10.8 +/- 7.0, respectively). Likewise, placebo (D5W) did not change DFT values from baseline values (10.1 +/- 4.5 vs 11.3 +/- 4.3). During treatment phase, DFT values were 99 +/- 28% of baseline values in the hypertonic saline solution group and 116 +/- 23% of baseline values in the D5W groups (p = 0.21). The administration of hypertonic saline solution also did not affect ventricular conduction velocity, right ventricular action potential duration, or right ventricular effective refractory period. These data indicate that hypertonic saline solution does not appreciably affect defibrillation efficacy or electrical treatment of ventricular fibrillation.

Animals↗

Hypertonic saline solutions in brain injury.

PURPOSE OF REVIEW: Hypertonic saline solutions have received renewed attention as effective agents for the treatment of cerebral edema and in brain resuscitation in a variety of brain injury paradigms. Although evidence of the beneficial action of hypertonic saline solutions in traumatic brain injury is robust, data supporting use in other conditions are only now mounting. RECENT FINDINGS: Osmotic properties of hypertonic saline solutions have been well studied in laboratory-based studies in animal models and in patients with acute brain injury. There are, in addition, emerging data on the extraosmotic actions on brain pathophysiology. This review cites baseline literature and provides new evidence of actions of hypertonic saline solutions: (a). in augmenting cerebral blood flow after subarachnoid hemorrhage, (b). as an antiinflammatory adjunct, and (c). utility in chemonucleolysis for intervertebral disc disease and treatment of seizures associated with severe hyponatremia. SUMMARY: Brain injury from diverse etiologies including trauma, ischemic stroke, global cerebral ischemia from cardiac arrest, intraparenchymal or subarachnoid hemorrhage, infection, or toxic-metabolic derangements are commonly encountered in the clinical setting. Many of these conditions are associated with cerebral edema with or without elevated intracranial pressure. Osmotherapy constitutes the cornerstone of medical therapy for such patients. Hypertonic saline solutions have received renewed attention in clinical practice as osmotic agents for cerebral resuscitation. This article reviews experimental and clinical evidence of the efficacy of hypertonic saline solutions and elaborates on their use in patients with acute neurologic injury. Important areas for current and future research are highlighted before the use of hypertonic saline solutions can be accepted for widespread use.

Brain Injuries↗

Induced sputum: comparison between isotonic and hypertonic saline solution inhalation in patients with asthma.

BACKGROUND: Sputum induction by hypertonic saline solution inhalation is widely used to study airways secretions in patients with asthma. However, hypertonic saline solution is a potent indirect bronchoconstrictor. STUDY OBJECTIVES: We studied the validity of isotonic saline solution (0.9%) inhalation as a means to induce sputum by comparing it to hypertonic saline solution (4.5%) inhalation. PATIENTS: Sixteen patients with moderate-to-severe asthma reporting a clinical history of mucus hypersecretion. METHODS: Subjects underwent sputum induction twice at 1-week intervals. Saline solution (hypertonic or isotonic) was inhaled for three periods of 5 min. The parameters assessed in sputum samples were cell counts, sodium, eosinophil cationic protein (ECP), and albumin concentrations, osmolality, and pro-matrix metalloproteinase (MMP)-9 activity by zymography. RESULTS: The maximal fall in peak expiratory flow during sputum induction was greater after inhalation of hypertonic saline solution than after inhalation of isotonic saline solution (p < 0.01). Each subject produced analyzable sputum on both visits. There were no statistically significant differences in total and differential sputum cell counts, and the reproducibility coefficients were high for eosinophils and neutrophils when comparing the two methods. Likewise, sputum levels of ECP and albumin as well as sputum pro-MMP-9 activity were not different between the two methods, and were highly reproducible as shown by high intraclass coefficients (Ri) of correlation (0.72, 0.74, and 0.77 for ECP, albumin, and pro-MMP-9, respectively). Sputum sodium concentrations and osmolality were higher after inhalation of hypertonic saline solution (p < 0.05). CONCLUSION: In patients with moderate-to-severe asthma reporting a clinical history of mucus hypersecretion, inducing sputum by isotonic or hypertonic saline solution inhalation leads to comparable results in eosinophil and neutrophil cell counts and fluid phase mediators/proteins.

Administration, Inhalation↗

Prevalence of nephrotoxicosis associated with a short-term saline solution diuresis protocol for the administration of cisplatin to dogs with malignant tumors: 61 cases (1987-1989).

The study reported here was undertaken to determine the nephrotoxicosis associated with the administration of cisplatin, an antineoplastic agent, to dogs when administered during 6-hour saline solution diuresis. Cisplatin (70 mg/m2 of body surface, IV, every 21 days) was given to 61 dogs with malignant neoplasia with a total of 185 doses in 1 (n = 9 dogs), 2 (n = 26 dogs), 3 (n = 4 dogs), 4 (n = 9 dogs), 5 (n = 2 dogs), and 6 (n = 11 dogs) treatments. The cisplatin was given over a 20-minute period after 0.9% NaCl solution (saline solution) was administered IV for 4 hours at a rate of 18.3 ml/kg of body weight/h. After the cisplatin infusion, saline solution diuresis was continued at the same rate for 2 hours. Before each treatment with cisplatin, dogs were evaluated with at least a physical examination, CBC, determination of serum urea nitrogen concentration, and in most cases, determination of serum creatinine concentration and urine specific gravity. Four of the 61 dogs (6.6%) developed clinically evident renal disease after 2 (1 dog), 3 (2 dogs), and 4 (1 dog) doses of cisplatin were administered. Three of the 4 dogs had preexisting disease of the urinary tract prior to the start of treatment. The survival time in dogs that developed renal disease (median, 145 days; range, 15 to 150 days) was similar to that of all dogs in this study (median, 154 days; range, 30 to 500 days), with 13 dogs still alive at the conclusion of the study.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Phenol-containing saline solution as a diluent for adenosine 5'-monophosphate in bronchial challenge testing.

OBJECTIVES: To investigate the effect of dissolving adenosine 5'-monophosphate (AMP) with phenol-containing saline solution on the stability and the bronchoconstrictive properties of this indirect agonist. METHODS: Eleven subjects with asthma well controlled with short-acting inhaled beta2-agonists as required or with inhaled corticosteroids were studied. Bronchial challenge tests with AMP dissolved with either normal saline solution or saline solution containing 0.4% phenol were performed on separate days. Furthermore, to assess the potential influence of the phenol-containing saline solution on the stability of the bronchoconstrictor agent, AMP solutions in concentrations of 40 microg/mL and 400 microg/mL were prepared in saline solution and phenol-containing saline solution and, after 30 min, the AMP levels were determined by high-performance liquid chromatography (HPLC) assay. RESULTS: The geometric mean AMP provocative concentration causing a 20% fall in FEV1 (PC20) was 13.49 mg/mL (95% confidence interval [CI], 6.76 to 26.91) for the saline solution method, and AMP PC20 for the saline solution with phenol method was 8.91 mg/mL (95% CI, 3.39 to 23.44) [p = 0.18]. No significant differences were found between the concentrations of AMP made in saline solution compared to those made in phenol-containing saline solution measured by HPLC. CONCLUSION: These observations indicate that normal saline solution with or without phenol can be used as the diluent for AMP. However, since a potential risk with AMP of industrial sources is the bacterial contamination, adding a preservative such as phenol to a saline solution diluent might be recommended.

Adenosine Monophosphate↗