Hypertonic saline decreases ciliary movement in human nasal epithelium in vitro.

Various saline solution formulae are frequently used in patients with rhinosinusitis. Osmolarity affects ciliary beat frequency (CBF); however, little is known about the effects of saline solutions on ciliary activity of nasal epithelial cells. The aim of this study was to assess whether CBF of normal turbinate mucosa is affected by hypertonic, isotonic, or hypotonic saline solution in vitro and whether histologic changes are associated with the alteration of ciliary movement. We assessed variations of CBF after exposure to 0.06%, 0.12%, 0.9%, 3.0%, or 7.0% saline solutions and histologic changes were examined by transmission electron microscopy. Isotonic and hypotonic solutions produced no ciliary slowing; however, ciliostasis was observed within a few minutes in 3.0% or 7.0% solution. The histologic changes demonstrated that the ciliary slowing might be attributed to epithelial damage by fluid transport toward the surrounding medium. In conclusion, hypertonic saline solutions decrease CBF and disrupt nasal epithelial cells in vitro.     

Regulation of the urine concentration mechanism by the oropharyngeal afferent pathway in man

BACKGROUND: It has been reported that the oropharyngeal afferent pathway behaves as a first-order factor regulating body fluid. However, the neural mechanism has not yet been clear. This study was designed to elucidate the characteristics of the neural mechanism in man. METHODS: Healthy human subjects kept either an isotonic or hypertonic solution in the oral cavity so as to moisten the oropharyngeal mucosa without intake for 20 min. Plasma vasopressin (AVP) concentration, urine volume and urine and plasma osmolalities were measured before and after the application. RESULTS: The oropharyngeal application of isotonic saline induced no significant changes in plasma AVP concentration, urine volume and osmolality, while that of hypertonic saline induced a significant decrease and increase in urine volume and osmolality, respectively. The plasma AVP concentration increased significantly after the application of hypertonic saline. Mannitol also induced a significant decrease and increase in urine volume and osmolality, respectively. However, the urinary responses after the application of mannitol were delayed compared with those of hypertonic saline. There were no significant changes in plasma osmolality before and after each application. CONCLUSION: These results suggest that the oropharyngeal afferent pathway from the oropharynx to hypothalamic AVP-producing cells takes part in the thirst mechanism regulating body fluid in humans. The oropharyngeal afferent signals may behave as sodium-chloride-sensitive osmoreceptor.     

Bioelectric effects of quinine on polarized airway epithelial cells.

Quinine has been increasingly utilized as a placebo in cystic fibrosis (CF) clinical trials, including those leading to FDA approval of inhaled tobramycin, recent studies of anti-inflammatory aerosols such as glutathione, and clinical testing of hypertonic saline aerosols to augment mucous clearance. The drug effectively masks taste of experimental therapeutics, but could also confer changes in processes contributing to CF pathogenesis, including chloride secretion and paracellular ion permeability. In the Ussing chamber, concentrations of quinine (1 mg/ml) anticipated in the airways of CF subjects after aerosolization led to changes in chloride transport in Calu-3 (airway serous glandular) cell monolayers. Tissue resistance was significantly disrupted by the compound in both Calu-3 and primary airway epithelial cells in vitro. Lower doses of quinine (between 10 and 100 microg/ml) strongly inhibited the chloride secretory mechanism that utilizes CFTR, and forskolin activated I(SC) was reduced by approximately 24% and 44% in the presence of 10 and 100 microg/ml quinine, respectively. Our findings indicate that quinine disrupts airway epithelial functional integrity and blocks transepithelial chloride transport. The use of quinine as a taste-masking agent may have bioelectric effects relevant to CF trials using aerosolized drug delivery.     

Effects of buffered saline solution on nasal mucociliary clearance and nasal airway patency.

OBJECTIVE: To compare the effects of buffered hypertonic and buffered normal saline nasal spray on mucociliary clearance and nasal airway patency. STUDY DESIGN AND SETTING: Double-blind trial with subjects acting as their own controls. Tertiary care academic medical center. RESULTS: Buffered hypertonic saline and buffered normal saline both improved saccharine clearance times ( P < 0.0001 for buffered hypertonic and P = 0.002 for buffered normal saline). Buffered hypertonic saline improved saccharine clearance times more than buffered normal saline (39.6% vs 24.1%, P = 0.007). Neither buffered hypertonic nor buffered normal saline significantly affected nasal airway patency. CONCLUSIONS: Both buffered hypertonic and buffered normal saline nasal spray significantly improved saccharine clearance times without affecting nasal airway patency. Buffered hypertonic saline affected saccharine clearance times to a greater degree than buffered normal saline. CLINICAL SIGNIFICANCE: Buffered hypertonic and buffered normal saline sprays both improve mucociliary clearance and should therefore be beneficial in conditions such as rhinitis and sinusitis, which are associated with disruption of mucociliary clearance. However, these sprays do not appear to affect the nasal airway. Patients may therefore benefit from other treatments for "nasal congestion." EBM rating: B-2.     

Bronchial hyperresponsiveness and the bronchiolitis obliterans syndrome after lung transplantation.

Because bronchial hyperresponsiveness has been linked to the bronchiolitis obliterans syndrome (BOS), we determined PD(20) methacholine (PD(20(M))), PD(15) hypertonic saline (PD(15(HS))) and their dose-response slopes (DRS(M) and DRS(HS)) in 8 single and 18 double lung transplant recipients within 1 year of lung transplantation and examined the relationship to bronchoalveolar lavage cell profiles and subsequent development of BOS. Twenty-two patients (81%) had a positive methacholine and 6 (25%) a positive hypertonic saline challenge. A positive PD(15(HS)) was associated with an increased risk for BOS at 2 years (odds ratio 12.6, 95% confidence interval 1.3-123.5, p < 0.05), and time to BOS was significantly and negatively related to DRS(HS) (r = -0.5, p < 0.05) - that is, the greater the response, the shorter the time to BOS. Interestingly, DRS(HS) correlated positively with recipient:donor total lung capacity ratio (r = 0.5, p < 0.05), but there was no relationship between either challenge result and airway inflammation. Methacholine hyperresponsiveness is common after lung transplantation but is not prognostic, whereas response to hypertonic saline may reflect recipient:donor size matching and provide useful information regarding the potential for BOS development.     

Relation of the hypertonic saline responsiveness of the airways to exercise induced asthma symptom severity and to histamine or methacholine reactivity.

BACKGROUND: Conflicting views exist over whether responsiveness of the airways to hypertonic saline relates to non-specific bronchial hyperresponsiveness measured by histamine or methacholine challenge. The bronchoconstrictor responses to exercise and hypertonic saline are reported to be closely related, but the relationship between the symptoms of exercise induced asthma and airway responsiveness to hypertonic saline is not known. METHODS: In 29 asthmatic patients with a history of exercise induced asthma, the response to an ultrasonically nebulised hypertonic saline (3.6% sodium chloride) aerosol, measured as the volume of hypertonic saline laden air required to produce a fall in forced expiratory volume in one second (FEV1) of > or = 20% (PD20), was compared with the concentration of histamine (PC20; group 1) and methacholine (PC20; group 2) producing a 20% fall in baseline FEV1 and exercise induced asthma symptom severity score (groups 1 and 2). The hypertonic responsiveness was determined in a dose-response manner to a maximum dose of 310 1 and the exercise induced asthma symptom severity was scored on a scale of 0-5. RESULTS: Of the 29 patients, 23 (79%) were responsive to the hypertonic saline, with PD20 values ranging from 9 to 310 1. A significant correlation was found between the PD20 hypertonic saline and the exercise induced asthma symptom score. There was no significant correlation between the PD20 response to hypertonic saline and the histamine PC20 or methacholine PC20. The exclusion of those subjects who failed to respond to hypertonic saline improved the relationship between hypertonic saline and methacholine PC20. No significant correlation was found between the exercise induced asthma symptom score and histamine PC20 or methacholine PC20. CONCLUSION: These findings suggest that hypertonic saline responsiveness bears a closer relationship to the severity of exercise induced asthma symptoms than to the non-specific bronchial hyperresponsiveness measured by histamine or methacholine reactivity.     

Prevention of the inhibitory effects of aspirin on sodium transport in canine gastric mucosa by prostaglandin. Correlation with mucosal morphology

Using an in vitro canine gastric mucosal preparation, this study evaluated the effects of 1 mM aspirin in a buffered Ringer solution (pH = 7.4), with and without concomitant prostaglandin (PG) treatment, on net sodium transport (mucosa to serosa) across gastric epithelium. Administration of aspirin to the mucosal bathing solution for 2 hr significantly decreased the potential difference (PD), short circuit current (Isc), and net sodium transport (net J-Na+) when compared with untreated control mucosa. In mucosa treated with 16,16-dimethyl PGE2 (8 X 10(-6) M) in the serosal bathing solution 40 min after aspirin exposure and for 80 min thereafter, the initial inhibitory effects on PD, Isc, and net J-Na+ induced by aspirin were completely reversed within 40 min of PG treatment, having returned to control values. Histologically, mucosa exposed to aspirin alone showed evidence of diffuse cellular injury involving 50-60% of the surface epithelium. In contrast, mucosa treated with prostaglandin in conjunction with aspirin exposure demonstrated damage involving only 20-30% of the epithelium. These findings suggest that stimulation of sodium transport by PG may play a role in mediating the cytoprotective effects of PGs against aspirin-induced gastric mucosal injury.     

The effect of saline solutions on nasal patency and mucociliary clearance in rhinosinusitis patients.

OBJECTIVE: To compare the effect of two saline nasal sprays on nasal patency and mucociliary clearance in patients with rhinosinusitis. STUDY DESIGN: Randomized double-blind trial. SUBJECTS AND METHODS: Eighty patients with rhinosinusitis at a tertiary care academic center had nasal patency and mucociliary clearance measured. Each patient was then treated with either physiological or hypertonic saline. Nasal patency and mucociliary clearance measurements were repeated after treatment. Subjective evaluation was also performed. RESULTS: Both solutions improved saccharine clearance times (P < 0.0001). Buffered physiological saline significantly affected nasal airway patency (P = 0.006). Both solutions improved symptoms of nasal stuffiness (P < 0.0001) and nasal obstruction (P < 0.0001). Buffered hypertonic saline caused increased nasal burning/irritation compared with buffered physiological saline (P < 0.0001). CONCLUSIONS: Buffered physiological and buffered hypertonic saline nasal sprays both improve mucociliary clearance, which is beneficial for treatment of rhinosinusitis. Additionally, buffered physiological saline improves nasal airway patency, whereas buffered hypertonic saline has no effect. Both solutions provide symptomatic relief, but buffered hypertonic saline is more irritating.     

Bronchial hyperresponsiveness in lung transplant recipients: lack of correlation with airway inflammation

BACKGROUND: Bronchial hyperresponsiveness (BHR) to methacholine has been reported to occur in most lung transplant recipients. BHR to physical stimuli such as exercise and non-isotonic aerosols has not been as extensively studied in this subject population. This report aims to assess the presence and degree of BHR to methacholine and hypertonic saline in stable lung transplant recipients and to relate it to the presence of airway inflammation. METHODS: Ten patients undergoing bilateral sequential lung transplantation and six heart-lung transplant recipients, all with stable lung function, were recruited 66- 1167 days following transplantation. Subjects underwent a methacholine challenge and bronchoscopy for sampling of bronchoalveolar lavage fluid, transbronchial and endobronchial biopsy tissues. Hypertonic saline challenge was performed six days later. RESULTS: Nine of the 16 transplant recipients had positive methacholine challenges (geometric mean PD20 0.18 mg, interquartile range 0.058-0.509) and three of these subjects also had positive hypertonic saline challenges (PD15 = 2.3, 33.0, and 51.5 ml). No clear relationship was found between BHR to either methacholine or hypertonic saline and levels of mast cells, eosinophils or lymphocytes in samples of biopsy tissue or lavage fluid. CONCLUSIONS: Most of the lung transplant recipients studied were responsive to methacholine and unresponsive to hypertonic saline. BHR was not clearly related to airway inflammation, suggesting an alternative mechanism for BHR following lung transplantation from that usually assumed in asthma.


     

Role of histamine release in hypertonic saline induced bronchoconstriction.

In a study designed to determine the protective effect of the specific histamine H1 antagonist terfenadine on hypertonic saline induced bronchoconstriction, 10 asthmatic subjects underwent hypertonic saline challenge (3.6%) after premedication with placebo or terfenadine (120 mg) 12 and two hours before the challenge. Hypertonic saline was administered in a dose dependent manner and the response determined as the dose of hypertonic saline that induced a 20% fall in FEV1 (PD20 FEV1). FEV1 was on average 11% greater with terfenadine than with placebo given before the challenge with hypertonic saline. PD20 FEV1 was attenuated by a mean of 2.5 fold after terfenadine (geometric mean PD20 FEV1 was 22 litres after placebo and 56 l after terfenadine). There was substantial intersubject variation in the inhibitory effect of terfenadine on hypertonic saline induced bronchoconstriction: the ratio of the PD20 hypertonic saline after terfenadine to that after placebo ranged from 0.9 to 10.0. Terfenadine inhibited histamine induced bronchoconstriction in the eight subjects in whom it was tested, by 13 to 160 fold compared with placebo in four subjects and by greater than 2 to greater than 9 fold in the four who showed no response to the highest dose of histamine given (16 mg/ml). These results suggest that histamine release has a role in hypertonic saline induced bronchoconstriction in some individuals; other mediators or mechanisms may have a more prominent role in others.     

Epithelial barrier formation by airway basal cells

BACKGROUND: Epithelial shedding processes in airway inflammation and defence may produce damaged areas where basal cells are the main remaining epithelial cell type. The present study examines the capacity of basal cells to form an epithelial barrier structure after loss of columnar epithelial cells. METHODS: A technique was developed which allows selective removal of columnar epithelial cells from isolated airways. A drop of tissue adhesive glue was applied on the mucosal surface shortly after excision of guinea pig trachea and human bronchus. Gentle removal of the glue, together with attached columnar cells, left a single layer of cobbled, solitary basal cells. The tissue was kept in culture media. Morphological changes of the basal cells were monitored by immuno-histochemistry and scanning and transmission electron microscopy at several time points. RESULTS: After 20 minutes the basal cells had undergone extensive flattening and established contact with each other. The basement membrane thus became covered by a poorly differentiated epithelium in both guinea pig and human airways. Abundant interdigitating cytoplasmic protrusions were observed at cell borders. CONCLUSIONS: Basal cells promptly flatten out to cover the basement membrane at loss of neighbouring columnar cells. These data may explain why the epithelial barrier function may be uncompromised in desquamative airway diseases. Furthermore, they suggest the possibility that sacrificial release of columnar epithelial cells and prompt creation of a barrier structure constitute important roles of basal cells in airway defence against severe insults.


     

Effects of nicotine on the human nasal mucosa.

BACKGROUND--Topical application of nicotine and stimulation of tachykinin containing sensory nerves have been shown to produce mucosal exudation of plasma and derangement of the epithelial lining in guinea pig and rat airways. If this occurred in man these effects might contribute to the pathogenesis of airway disease. This study, performed in healthy volunteers without atopy, examined whether nicotine affects the plasma exudation response and the mucosal absorption permeability of the human nasal airway. METHODS--The acute effects of increasing topical doses of nicotine (0.08-2.0 mg) were examined (n = 8) on nasal symptoms (pain), mucosal exudation of plasma (albumin), mucosal secretion of mucin (fucose), and mucosal exudative responsiveness (histamine induced mucosal exudation of albumin). A separate placebo controlled study was carried out to determine whether frequent applications of the high dose of nicotine (2.0 mg given eight times daily for nine days) had any deleterious effects on the airway mucosa detectable as altered responses to histamine challenge. Both mucosal exudation of plasma (n = 12) and mucosal absorption of chromium-51 labelled EDTA (n = 8) were thus examined in nasal airways exposed to both nicotine and histamine. RESULTS--Nicotine caused nasal pain and produced dose dependent mucosal secretion of fucose but failed to produce any mucosal exudation of albumin. The exudative responsiveness to histamine was, indeed, decreased when the challenge was performed immediately after administration of acute doses of nicotine, whereas the responsiveness was unaffected when histamine challenges were carried out during prolonged treatment with nicotine. The nasal mucosal absorption of 51Cr-EDTA in the presence of histamine did not differ between subjects receiving either placebo or nicotine treatment for nine days. CONCLUSIONS--The results indicate that nicotine applied to the human airway mucosa produces pain and secretion of mucin, but inflammatory changes such as mucosal exudation of plasma and epithelial disruption may not be produced. Neurogenic inflammatory responses, which are so readily produced in guinea pig and rat airways, may not occur in human airways.     

Differences in the physiological response and ultrastructure of human and guinea pig vas deferens. Effects of prostaglandins, irradiation, and temperature

Marked differences were observed in the mechanical reactions of human and guinea pig vas deferens to prostaglandins, irradiation, and cooling. In human preparations prostaglandin E1 (0.1-1 ng/ml) had an augmentory effect on the contractile response after electrical neurostimulation (10 Hz, 0.3 ms, 3 s), but no visible influence (at concentrations ranging from 1 ng to 10 micrograms/ml) on the contractile response after electrical muscle stimulation (10 Hz, 40 ms, 3 s). In contrast, in guinea pig preparations (PGE1 (0.1-1 ng/ml) had an inhibitory effect on the contractile response after electrical neurostimulation and an augmentory effect (0.1-1 micrograms/ml) on the contractile response after electrical muscular stimulation. Human vas deferens showed higher radiosensitivity than guinea pig preparations. The neurotransmitters acetylcholine and catecholamines increased the radiosensitivity of guinea pig preparations, but not of human ones. Vas deferens reacted to short-time (15-120 s) cooling with an immediate temporary contraction, at 25 degrees C of short (seconds), at 5 degrees C of long (minutes) duration; after rewarming (5-37 degrees C) a second contraction appeared in guinea pig preparations, but not in human ones. Whereas the contraction to electrical neurostimulation (10 Hz, 0.3 ms, 3 s) was abolished in human preparations by cooling, it was only inhibited in guinea pig vas deferens. Electron microscopy showed differences in the ultrastructure of human and guinea pig vas deferens. Muscle cells were more widely separated in human vas deferens (generally 400 nm or more) than in guinea pig (approximately 100-200 nm), and the intracellular space in human preparations contained more collagen. The axons in human preparations contained predominantly large granular and agranular vesicles, those in guinea pig preparations small granular and agranular vesicles. The possible correlation between the physiological response of human and guinea pig vas deferens and the ultrastructural differences is discussed. The results indicate the possibility that other pharmacophysiological and toxicological phenomena could be essentially different in human and guinea pig material.     

The effects of hypertonic saline solution (7.5%) on coagulation and fibrinolysis: an in vitro assessment using thromboelastography

We studied the effects of hypertonic (7.5%) and normal saline on coagulation and fibrinolysis in an in vitro model using thromboelastography of human whole blood. Reaction times increased and alpha angles decreased with hypertonic saline replacement at 7.5% blood volume compared with similar dilution with normal saline. At 10% blood volume replacement with hypertonic saline, reaction and coagulation times were significantly increased and alpha angles were decreased. Clot lysis at 30 min was also significantly reduced. We conclude that 7.5% hypertonic saline solution has anticoagulant effects if it replaces 7.5% or more of blood volume.     

Effect of hypertonic saline solution on the left ventricular functions of isolated hearts from burned rats

Objective: To study the effect of hypertonic saline solution on the left ventricular functions of isolated hearts from Imrned rats. Methods: Thirty-six Wistar rats were used and divided into 4 groups: (1) normal hearts perfused with isotonic Krebs-Henseleit solution; ( 2 ) normal hearts perfused with Krebs-Henseleit solution which contained 215 mmoVL Na^ ; (3) hearts of rats suffered from 25% TBSA third degree burn and perfnsed with isotonic Krebs-Hensekit solution; (4) hearts of the burned rats perfused with Krebs-Henseleit solution which contained 215 mmol/L Na^ . The systolic and diastolic functions of the left ventricle were observed. Results: During perfusion, there were very short periods of decrease in heart systolic and diastolic functions at first, but they recovered very soon and even became stronger than normal both in the normal and burned rats.The systolic and diastolic functions of the hearts increased very siLmificantly when the perfusion solution was changed to isotonic solution from the hypertonic solutions. The effect of the hypertonic s.gline solution on the ventricular systolic and diastolic improvements was stronger in the hearts of the burned rats than that in the normal hearts. Conclusions: Hypertonic saline solution can directly affect myocardium and significantly improve the ventricular systolic and diastolic functions, especially in the hearts of the burned rats.     

Treating ischemic left ventricular dysfunction with hypertonic saline administered after coronary occlusion in pigs

OBJECTIVE(S): The effects of hypertonic saline on ventricular function are controversial, whether it is increasing contractility or preload. There are no data, however, on the influence of hypertonic saline in a stunned myocardium. DESIGN: This study was prospective and randomized in order to analyze the effects of hypertonic saline solution (7.5%) on myocardial function and systemic hemodynamics in a porcine model of ischemia and reperfusion. SETTING: A university teaching hospital, animal research laboratory. PARTICIPANTS: Twelve adult domestic swine. INTERVENTIONS: Myocardial stunning was produced by the complete occlusion of the proximal left anterior descending artery for 15 minutes followed by reperfusion. Five minutes after reperfusion, the animals were assigned to receive 4 mL/kg of hypertonic saline (n = 7) or normal saline (n = 5) over 10 minutes. Pressure-tipped catheters were placed in the left ventricular cavity and aorta. The dimensions of the left ventricle were measured with ultrasonic microcrystals. Cardiac output was measured with transit time ultrasound. Data were recorded continuously and compared before the occlusion, 5 minutes after reperfusion, and at the end of the infusion. MEASUREMENTS AND MAIN RESULTS: Compared with baseline, ventricular function was significantly depressed after left anterior descending artery occlusion. Left ventricular dP/dT and its end-systolic pressure-volume slope decreased (38% and 52%, respectively; p < 0.05), with a concomitant increase in systemic vascular resistance. The administration of hypertonic saline significantly improved left ventricular function (Emax 1,422 +/- 198 mmHg/mL, and dP/dT 3.2 +/- 0.4 mmHg/s v normal saline group values of 1,156 +/- 172 and 2.5 +/- 0.5, respectively; p < 0.05), cardiac output (2.5 +/- 0.5 v 1.84 +/- 0.4 L/min, p < 0.05), and lowered systemic vascular resistance (from 28.8 +/- 2.3 to 23.5 +/- 1.4, p < 0.05), with no significant changes with normal saline administration. CONCLUSIONS: After transient myocardial ischemia, hypertonic saline administered over a short period of time acts as an inodilator by increasing contractility while simultaneously lowering systemic vascular resistance.     

Small-volume resuscitation with hypertonic saline dextran solution

Small-volume hypertonic resuscitation has been proposed as an effective means for restoration of cardiovascular function after hemorrhage at the scene of an accident. We evaluated the cardiovascular, metabolic, and neurohumoral response of resuscitation after hemorrhage using 200 ml of 2400 mosm sodium chloride, 6% dextran 70. Unanesthetized adult sheep were bled to maintain mean arterial pressure at 50 mm Hg for 3 hours, shed blood volume = 42 +/- 7 ml/kg. The sheep were then treated with a single bolus infusion of hypertonic saline dextran (n = 7) or normal saline solution (control group, n = 7) and then observed for a 30-minute period of simulated patient transport during which no additional fluid was given. Hypertonic saline dextran caused rapid restoration of blood pressure and cardiac output within 2 minutes of infusion. Cardiac output remained at or above baseline level, while both O2 consumption and urine output increased to above baseline level during the 30 minutes of simulated patient transport. By comparison 200 ml of normal saline solution caused only a small increase in blood pressure and no improvement in cardiac output or oxygen consumption. After this 30-minute period, both groups were given lactated Ringer's solution as needed to return and maintain cardiac output at its baseline value. The volume of lactated Ringer's solution required to maintain cardiac output was less in the hypertonic group, 371 +/- 168 ml, only one sixth that of the control group, 2200 +/- 814 ml. In summary after 3 hours of hypovolemia, a small volume of hypertonic saline dextran, about 4 ml/kg, fully restored cardiovascular and metabolic function for at least 30 minutes and significantly lowered the total volume requirements of resuscitation.     

Effect of regular inhaled salbutamol on airway responsiveness and airway inflammation in rhinitic non-asthmatic subjects

BACKGROUND: Regular, inhaled beta 2 agonists may increase airway responsiveness in asthmatic subjects. The mechanism is not known but may be via an increase in airway inflammation. A study was undertaken to examine the effect of regular inhaled salbutamol on airway responsiveness to methacholine and hypertonic saline, on the maximal response plateau to methacholine, and on inflammatory cells in induced sputum in rhinitic non-asthmatic subjects. METHODS: Thirty subjects with a baseline maximal response plateau of > 15% fall in forced expiratory volume in one second (FEV1) entered a randomised, placebo controlled, parallel trial consisting of two weeks run in, four weeks of treatment, and two weeks washout. Methacholine challenges were performed at the beginning of the run in period, before treatment, after treatment, and after washout. Hypertonic saline challenges were performed before and after treatment and induced sputum samples were collected for differential cell counting. RESULTS: There was no change in airway responsiveness, maximal response plateau to methacholine, or in induced sputum eosinophils or mast cells. The maximum fall in FEV1 after hypertonic saline increased in the salbutamol group (median change 6.0%, interquartile range (IQR) 11.0) but did not change in the placebo group (median change 1.3%, IQR 5.5). CONCLUSIONS: Regular inhaled salbutamol for four weeks increases airway responsiveness to hypertonic saline but does not alter airway responsiveness to methacholine or cells in induced sputum in non-asthmatic individuals with rhinitis. The relevance of these findings to asthmatic subjects has not been established.


     

Use of mometasone furoate aqueous nasal spray in the treatment of rhinitis medicamentosa: an experimental study.

OBJECTIVE: We aimed to investigate, histopathologic changes in the nasal mucosa of guinea pig's after prolonged administration of oxymetazoline and the development of rhinitis medicamentosa, and the efficacy of mometasone furoate aqueous nasal spray and saline in reversing the ultrastructural changes attributable to rhinitis medicamentosa. METHODS: In the study, 24 male guinea pigs (500 to 600 gr) were used. Oxymetazolin (0.05%) was sprayed into the nasal cavities of the guinea pigs 3 times daily for 8 weeks. At the end of this period, 6 guinea pigs were killed and examined to make sure that the animals had developed rhinitis medicamentosa. The remaining guinea pigs were randomly divided into 3 groups. In the first group, one spray-puff of 0.05% mometasone furoate aqueous nasal spray (50 microg) was applied twice daily for 14 days. In the second group, saline solution (0.9% NaCl) was applied twice daily for 14 days. No treatment was performed in the third group. At the end of the treatment period, nasal mucosal changes were evaluated by light microscopy and electron microscopy. RESULTS: After oxymetazolin application for 8 weeks, the main histologic changes were edema, congestion, proliferation of subepithelial glands, and squamous cell metaplasia. After topical mometasone furoate aqueous spray application for 2 weeks, the edema fluid was found to diminish markedly. In the saline and no treatment groups, edema and congestion continued. In these groups of guinea pigs, fibrosis has been seen in the nasal mucosa. CONCLUSION: We found that mometasone furoate nasal spray was effective against experimentally induced rhinitis medicamentosa in guinea pigs. Mometasone furoate nasal spray may have value in the treatment of patients with rhinitis medicamentosa.     

Effects of hypertonic saline versus lactated Ringer's solution on cerebral oxygen transport during resuscitation from hemorrhagic shock

Hypertonic saline successfully restores systemic hemodynamics in dogs and humans with severe hemorrhagic shock and, in contrast to lactated Ringer's solution, does not increase intracranial pressure (ICP). This study compares cerebral oxygen delivery in 12 dogs subjected to hemorrhagic shock by the rapid removal of blood (mean arterial pressure of 40 mm Hg maintained for 30 minutes), and then resuscitated with lactated Ringer's solution (six dogs) or 7.5% saline solution (six dogs) to restore systolic arterial pressure. Both solutions effectively restored systemic hemodynamic stability, increasing cardiac output and systolic blood pressure while decreasing mean and diastolic arterial pressure and systemic vascular resistance. The ICP was significantly lower after resuscitation in the hypertonic saline group (p less than 0.05), but cerebral blood flow, which had decreased during shock, was not restored by either fluid, and cerebral oxygen transport fell further secondary to a hemodilutional reduction of hemoglobin. Although hypertonic saline may improve systemic hemodynamics and maintain a low ICP during resuscitation, it fails, as does Ringer's solution, to restore cerebral oxygen transport to prehemorrhagic shock levels.