Biomedical subjects

Yochai Adir

Publications and source records attributed to Yochai Adir.

At least 19 recordsLinked to original sources

PubMed2006

Alveolar fluid reabsorption is increased in rats with compensated heart failure.

Alveolar fluid reabsorption (AFR) is important in keeping the air spaces free of edema. This process is accomplished via active transport of Na(+) across the alveolo-capillary barrier mostly by apical Na(+) channels and basolateral Na(+)-K(+)-ATPases. Recently, we have reported that acute elevation of left atrial pressures is associated with decreased AFR in isolated rat lungs. However, the effect of chronic elevation of pulmonary capillary pressure, such as seen in patients with congestive heart failure (CHF), on AFR is unknown. CHF was induced by creating an aorto-caval fistula (ACF) in Sprague-Dawley male rats. Seven days after the placement of the fistula, AFR was studied in the isolated perfused rat lung model. AFR in control rats was 0.49 +/- 0.02 ml/h (all values are means +/- SE) and increased by approximately 40% (0.69 +/- 0.03 ml/h) in rats with chronic CHF (P < 0.001). The albumin flux from the pulmonary circulation into the air spaces did not increase in the experimental groups, indicating that lung permeability for large solutes was not increased. Na(+)-K(+)-ATPase activity and protein abundance at the plasma membrane of distal alveolar epithelial tissue were significantly increased in CHF rats compared with controls. These changes were associated with increased plasma norepinephrine levels in CHF rats compared with controls. We provide evidence that in a rat model of chronic compensated CHF, AFR is increased, possibly due to increased endogenous norepinephrine upregulating active sodium transport and protecting against alveolar flooding.

Adrenalectomy↗

PubMed2006

Hemodynamic effects of combined treatment with oxygen and hypertonic saline in hemorrhagic shock.

OBJECTIVE: In hemorrhagic shock, small volume resuscitation with hypertonic saline transiently increases mean arterial blood pressure (MABP) and cardiac output and augments organ perfusion. Inhalation of 100% oxygen after hemorrhage also increases MABP and redistributes blood flow to the splanchnic and renal vascular beds. We evaluated hemodynamic effects of combined resuscitation with hypertonic saline and oxygen in shock induced by controlled bleeding in rats. DESIGN: Animal study. SETTING: Research laboratory. SUBJECTS: Male Sprague-Dawley rats. INTERVENTIONS: Animals were assigned to four hemorrhage groups that received posttreatment with a) normal saline; b) normal saline + 100% oxygen; c) hypertonic saline; d) hypertonic saline + oxygen, and a fifth sham-shock group that received hypertonic saline + oxygen. MEASUREMENTS AND MAIN RESULTS: Bolus infusion of small volume hypertonic saline markedly increased MABP (p < .001), hindquarter vascular resistance (p < .05), and distal aorta blood flow (p < .01). Hypertonic saline transiently increased superior (cranial) mesenteric artery (SMA) blood flow (p < .001) and small bowel perfusion (p < .01). Inhalation of oxygen after normal saline rapidly increased MABP (p < .01) and hindquarter vascular resistance (p < .02) and decreased distal aorta blood flow (p < .02) and perfusion of the gracilis muscle (p < .05). When given after normal saline, oxygen did not change SMA resistance and increased SMA flow (p < .05). The supplementation of oxygen after hypertonic saline did not exert additional effects on vascular resistance and blood flows in the two vascular beds. However, the combined treatment prevented the oxygen-induced decrease in distal aorta blood flow and gracilis muscle perfusion and maintained MABP at slightly higher values and SMA flow at significantly higher values than hypertonic saline alone until the end of the protocol (p < .01). The two hemorrhaged groups treated with oxygen exhibited the lowest final plasma lactate concentrations (p < .05 from normal saline and hypertonic saline groups). CONCLUSIONS: We suggest that early combined use of hypertonic saline and oxygen exerts a favorable extended profile of hemodynamic effects that amends shortcomings of each treatment alone in hemorrhagic shock.

Analysis of Variance↗

PubMed2006

Proteinuria on dipstick urine analysis after sexual intercourse.

OBJECTIVE: To examine the role of sexual intercourse as a cause of proteinuria, and establishes its duration, as a knowledge of benign causes of proteinuria is required to avoid unnecessary testing. SUBJECTS AND METHODS: Twenty-four married couples were instructed to produce a urine sample before and after sexual intercourse; their urine was tested for proteinuria by dipstick analysis. RESULTS: Samples were assayed from 22 men and 11 women. Whereas none of the 24 men originally assessed for the study had proteinuria before sexual intercourse, six of the 22 who were eventually enrolled had proteinuria after intercourse (27.3%, 95% confidence interval, 10-50%; P = 0.008). None of the women had proteinuria after sexual intercourse (95% confidence interval, 70-100%). The time to disappearance of proteinuria was <12 h. CONCLUSION: Sexual intercourse is confirmed as a benign cause of proteinuria in men. Whenever possible, it is wise to avoid sexual intercourse at least 12 h before urinary dipstick testing.

Coitus↗

PubMed2006

CNS toxicity in closed-circuit oxygen diving: symptoms reported from 2527 dives.

INTRODUCTION: Oxygen toxicity is a problem in diving and can have fatal consequences in the water. Various aspects of oxygen diving have been studied in dry hyperbaric chambers, but there is a lack of information on in-water diving using closed-circuit oxygen apparatus. METHOD: We collected 2527 dive reports from 473 closed-circuit oxygen divers (a mean of 5.2 reports per diver), and analyzed the relationships between various symptoms and their dependence on depth and diving time. RESULTS: No CNS oxygen toxicity-related symptoms were reported at a depth of 2 m seawater (msw), but their proportion increased at depths from 3 to 6 msw. We found that CNS oxygen toxicity-related symptoms appeared in 2.5% of dives conducted at a Po2 of 119 kPa. The main symptoms and signs reported were headache: 4.5%; nausea: 2.6%; hyperventilation: 2.6%; heavy breathing: 2.4%; dizziness: 1.6%; hiccups: 1.5%; bloody sputum: 1.4%; cold shivering: 1.1%; tinnitus: 0.9%; difficulty maintaining a steady depth: 0.9%; disorientation: 0.6%; tiredness: 0.5%; tingling in the limbs: 0.4%; hearing disturbances: 0.4%; a choking sensation: 0.4%; extreme effort: 0.4%; and loss of consciousness: 0.3%. DISCUSSION: Environmental factors, light vs. dark and temperature, had no effect on symptoms. The number of symptoms increased with diving time. Divers who experienced amnesia, facial twitching, hearing disturbances (p < 0.001), and disorientation (p < 0.014) were prone to suffer loss of consciousness. It was found that some divers are more sensitive to oxygen than others (p < 0.0001).

Airway Obstruction↗

PubMed2006

CO2 detection in closed-circuit oxygen divers with and without a distracting task.

INTRODUCTION: Elevated arterial PCO2 (hypercapnia) increases the risk of CNS oxygen toxicity when diving with enriched oxygen gas mixtures. A CO2 detection and retention test is conducted as a matter of routine at the Israel Naval Medical Institute for physiological training, and as a screening tool for divers who may be prone to suffer from CNS oxygen toxicity. This test does not include an "attention distracter", which would provide a better simulation of the true situation during actual diving. The purpose of the present study was to examine the hypothesis that the addition of cognitive tasks to the CO2 detection and retention test might alter divers' detection ability. METHODS: We assessed ventilatory and perceptual responses to variations in inspired CO2 (range 0-5.6 kPa, 0-42 mmHg) during moderate exercise, with and without the addition of cognitive tasks, in 15 Israel Navy combat divers on active duty. The first stage was the CO2 detection training session, followed by the CO2 detection test session (TEST) and the CO2 detection test session while doing cognitive tasks (COGN). The latter two sessions were performed by some of the subjects in reverse order. RESULTS: We found that the mean (+/- SD) PICO2 at the detection threshold was significantly lower in the COGN (1.7 +/- 0.8 kPa, 12.7 +/- 6.0 mmHg) than in the TEST (2.4 +/- 0.6 kPa, 18.1 +/- 4.5 mmHg). The mean PETCO2 while inspiring 5.6 kPa (42 mmHg) CO2 was not significantly different in the two tests. CONCLUSION: We suggest that the ability to detect CO2 during a dive is not impaired, but rather improves when the diver's attention is focused on other tasks.

Carbon Dioxide↗

PubMed2005

Interdependency of beta-adrenergic receptors and CFTR in regulation of alveolar active Na+ transport.

Beta-adrenergic receptors (betaAR) regulate active Na+ transport in the alveolar epithelium and accelerate clearance of excess airspace fluid. Accumulating data indicates that the cystic fibrosis transmembrane conductance regulator (CFTR) is important for upregulation of the active ion transport that is needed to maintain alveolar fluid homeostasis during pulmonary edema. We hypothesized that betaAR regulation of alveolar active transport may be mediated via a CFTR dependent pathway. To test this hypothesis we used a recombinant adenovirus that expresses a human CFTR cDNA (adCFTR) to increase CFTR function in the alveolar epithelium of normal rats and mice. Alveolar fluid clearance (AFC), an index of alveolar active Na+ transport, was 92% greater in CFTR overexpressing lungs than controls. Addition of the Cl- channel blockers NPPB, glibenclamide, or bumetanide and experiments using Cl- free alveolar instillate solutions indicate that the accelerated AFC in this model is due to increased Cl- channel function. Conversely, CFTR overexpression in mice with no beta1- or beta2-adrenergic receptors had no effect on AFC. Overexpression of a human beta2AR in the alveolar epithelium significantly increased AFC in normal mice but had no effect in mice with a non-functional human CFTR gene (Deltaphi508 mutation). These studies indicate that upregulation of alveolar CFTR function speeds clearance of excess fluid from the airspace and that CFTRs effect on active Na+ transport requires the betaAR. These studies reveal a previously undetected interdependency between CFTR and betaAR that is essential for upregulation of active Na+ transport and fluid clearance in the alveolus.

Animals↗

PubMed2005

Inner ear decompression sickness and mal de debarquement.

OBJECTIVE: To present a case series of vestibular symptoms appearing after combined sailing and diving activity, and to discuss the differential diagnosis and the workup algorithm. STUDY DESIGN: Case series. SETTING: Tertiary referral center. PATIENTS: Three patients aged 25 to 31 years suffering from unsteadiness and movement sensations after sailing and scuba diving. INTERVENTIONS: Neurotologic evaluation and recompression therapy in a hyperbaric chamber. MAIN OUTCOME MEASURES: The increasing popularity of marine sports and leisure activities has resulted in the exposure of a growing number of people to unique abnormalities not encountered under terrestrial conditions. The otolaryngologist who is involved in the care of these patients is required to diagnose and treat diving-related sinus and ear injuries such as barotrauma and decompression sickness, and also to be familiar with sailing-related disorientation syndromes such as seasickness and mal de debarquement. Treatment modalities for the various abnormalities differ significantly, and early commencement of treatment is often crucial for a successful outcome. CONCLUSION: Whenever doubt exists, recompression treatment must be instituted as soon as possible because of the potential for severe sequelae if the patient is left untreated, and because the risks involved in this therapy are minimal.

Adult↗

PubMed2005

Aural barotrauma in submarine escape: is mastoid pneumatization of significance?

OBJECTIVE: Submarine escape training is carried out by preselected, healthy young men under strictly controlled conditions regarding exposure to pressure and the rate of pressure change. This provides a unique opportunity to investigate the relations between middle ear characteristics and susceptibility to barotrauma while avoiding possible confounding parameters. We examined a possible association between mastoid pneumatization and middle ear barotrauma (MEB) in submarine escape trainees. STUDY DESIGN: Cross-sectional, parallel-group design. METHODS: Sixty-six subjects aged 19 to 28 participated in the study. The escape simulation included pressurization to 30 or 60 feet followed by a buoyant ascent to the surface. Subjects were evaluated for MEB after each ascent. A Schuller's mastoid radiograph was taken for the evaluation of mastoid pneumatization. RESULTS: Fifteen (23%) of the subjects suffered from MEB, and 6 (40%) of them had bilateral involvement. Repeated impedance audiometry after the completion of a successful ascent revealed a significant increase in middle ear compliance. Schuller's radiographs were obtained from 49 (74%) of the subjects. Of these radiographs, 16 (16%) were of ears that had suffered MEB. Mastoid pneumatization for all ears approached a normal Gaussian distribution, with a mean area of 9.58 cm. The mastoid areas and the proportion of ears with mastoid pneumatization at the extremes of the study population did not differ between barotrauma and no-barotrauma ears. CONCLUSION: In a population with no history of recurrent or chronic otitis media and normal tympanic membrane morphology and compliance, the amount of mastoid pneumatization probably represents merely the normal distribution of variation in organ size and is not related to the ability to equalize pressure in the middle ear.

Acoustic Impedance Tests↗

PubMed2005

Large lungs in divers: natural selection or a training effect?

BACKGROUND: Normal spirometry is required for medical clearance of professional divers in many countries. Divers frequently have unusually large lung volumes associated with a low ratio of FEV(1) to FVC (FEV(1)%), suggestive of obstructive airways disease. We retrospectively analyzed the records of divers in the Israeli Navy with a low FEV(1)% who fulfilled the criteria for large lungs, to determine whether this might be the effect of training or natural selection. We also investigated changes in pulmonary function in relation to diving experience. METHODS: A total of 171 divers with FEV(1)% < 80% on simple spirometry were evaluated. We conducted a retrospective analysis of lung function data for those subjects who met the criteria for large lungs. RESULTS: One hundred nine of 171 divers with low FEV(1)% met the criteria for large lungs and were included in the study. Their average age was 25 years (range, 18 to 44 years), and their mean diving experience was 7 years (range, 0 to 26 years). No difference was found in FVC values between experienced and inexperienced divers. The mean forced expiratory flow at 50% of vital capacity was significantly reduced in the most experienced group compared with the novice or less experienced divers. No difference was found in the diffusing capacity of the lung for carbon monoxide between experienced and inexperienced divers. CONCLUSIONS: We suggest that large lungs may represent part of the natural selection for diving, rather than a training effect. Prolonged diving experience may result in the development of small airways disease.

Adolescent↗

PubMed2005

Hyperbaric oxygen in the treatment of carbon monoxide poisoning.

Carbon monoxide, a byproduct of incomplete hydrocarbon combustion, has been responsible for many accidental poisonings worldwide. The signs and symptoms of poisoning are diverse, ranging from headache, dizziness, and confusion to cardiac and neurological disturbances. Oxygen is the cornerstone of treatment, because it accelerates the dissociation of carbon monoxide from heme proteins. The role of hyperbaric oxygen in the treatment of CO poisoning is still questionable. Only a few randomized, controlled studies have been conducted, and their results are inconsistent. In the present review, we discuss the conclusions of four randomized controlled studies and propose a hyperbaric oxygen treatment protocol based on these conclusions.

Carbon Monoxide Poisoning↗

PubMed2005

Scopolamine patch to prevent seasickness: clinical response vs. plasma concentration in sailors.

INTRODUCTION: Scopolamine is highly effective for the treatment of seasickness. Nevertheless, transdermal therapeutic system (TTS) scopolamine, despite high compliance on the part of persons treated by the drug, fails to provide protection against seasickness in 26-38% of patients. To the best of our knowledge, the correlation between scopolamine levels in plasma and its therapeutic effect under sailing conditions in the open sea is investigated for the first time in the present study. METHODS: Subjects were 61 crewmembers of naval vessels treated by TTS scopolamine. The therapeutic response at sea was documented by questionnaire. During a period ashore, a TTS scopolamine patch was applied in the same subjects. Blood samples were taken and an adverse effects questionnaire completed 8 h after scopolamine patch application. Scopolamine levels were determined using an established radio-receptor assay procedure. To verify the reproducibility of these measurements, blood samples were taken twice from most subjects, on separate days after different patch applications. Subjects were divided into "responders," who reported at least a moderate decrease in seasickness severity compared with their previous experience at sea without TTS scopolamine therapy, and "non-responders," who had only slight symptomatic relief or no relief at all. RESULTS: The mean scopolamine concentration in the plasma of the 37 responders (156.77 +/- 77.03 pg x ml(-1)) was significantly higher than the mean level in the 24 non-responders (97.03 +/- 73.34 pg x ml(-1); p = 0.005, simple t-test). CONCLUSIONS: Attempts to increase scopolamine levels in plasma by increasing the drug dosage or improving transdermal absorption should be considered for the treatment of "non-responders".

Absorption↗

PubMed2004

Response to CO2 in novice closed-circuit apparatus divers and after 1 year of active oxygen diving at shallow depths.

Elevated arterial Pco(2) (hypercapnia) has a major effect on central nervous system oxygen toxicity in diving with a closed-circuit breathing apparatus. The purpose of the present study was to follow up the ability of divers to detect CO(2) and to determine the CO(2) retention trait after 1 year of active oxygen diving with closed-circuit apparatus. Ventilatory and perceptual responses to variations in inspired CO(2) (range: 0-5.6 kPa, 0-42 Torr) during moderate exercise were assessed in Israeli Navy combat divers on active duty. Tests were carried out on 40 divers during the novice oxygen diving phase (ND) and the experienced oxygen diving phase. No significant changes were found between the two phases for the minimal mean inspired Pco(2) that could be detected. The mean (with SD in parentheses) end-tidal Pco(2) during exposure to an inspired Pco(2) of 5.6 kPa (42 Torr) was significantly higher in the novice diving phase than in the experienced diving phase [8.1 kPa (SD 0.7), 62 Torr (SD 5) and 7.8 kPa (SD 0.6), 59 Torr (SD 4), respectively; P < or = 0.001]. One year of shallow oxygen diving activity with a closed-circuit apparatus does not affect the ability to detect CO(2) nor does it lead to increased CO(2) retention; rather, it may even bring about a decrease in this trait. This finding suggests that acquiring experience in oxygen diving with a closed-circuit apparatus at shallow depths does not place the diver at a greater risk of central nervous system oxygen toxicity due to CO(2) retention.

Adult↗

PubMed2004

Gene transfer of the Na+,K+-ATPase beta1 subunit using electroporation increases lung liquid clearance.

The development of nonviral methods for efficient gene transfer to the lung is highly desired for the treatment of several pulmonary diseases. We have developed a noninvasive procedure using electroporation to transfer genes to the lungs of rats. Purified plasmid (100-600 microg) was delivered to the lungs of anesthetized rats through an endotracheal tube, and a series of square-wave pulses were delivered via electrodes placed on the chest. Relatively uniform gene expression was observed in multiple cell types and layers throughout the lung, including airway and alveolar epithelial cells, airway smooth muscle cells, and vascular endothelial cells, and this finding was dose- and pulse length-dependent. Most important, no inflammatory response was detected. To demonstrate efficacy of this approach, the beta1 subunit of the Na(+),K(+)-ATPase was transferred to the lungs of rats with or without electroporation, and 3 days later, alveolar fluid clearance was measured. Animals electroporated with the beta1 subunit plasmid showed a twofold increase in alveolar fluid clearance and Na(+),K(+)-ATPase activity as compared with animals receiving all other plasmids, with or without electroporation. These results demonstrate that electroporation is an effective method to increase clearance by introducing therapeutic genes (Na(+),K(+)-ATPase) into the rat lung.

Adenoviridae↗

PubMed2004

Norepinephrine increases alveolar fluid reabsorption and Na,K-ATPase activity.

The purpose of this study was to determine whether alpha-adrenergic receptor agonists have a role in alveolar fluid reabsorption, via Na,K-ATPase, in the alveolar epithelium. Alveolar fluid reabsorption increased approximately twofold with increasing concentrations of norepinephrine (NE) as compared with control rats. Treatment with the nonselective alpha-adrenergic receptor agonist, octopamine, and the specific alpha(1) agonist, phenylephrine, increased alveolar fluid reabsorption by 54 and 40%, respectively, as compared with control. The specific alpha(1)-adrenergic receptor antagonist, prazosin, inhibited the stimulatory effects of NE by approximately 30%, whereas alpha(2)-adrenergic antagonist, yohimbine, did not prevent the stimulatory effects of NE. The administration of ouabain, Na,K-ATPase inhibitor, prevented the NE-mediated increase in alveolar fluid reabsorption. In parallel with these changes, NE increased Na,K-ATPase activity and protein abundance in alveolar epithelial type II cells via the alpha(1)- and beta-adrenergic receptor. We report here that NE increased alveolar fluid reabsorption via the activation of both alpha(1)- and beta-adrenergic receptors, but not alpha(2)-adrenergic receptors. These effects are due to increased activity and abundance of the Na,K-ATPase in the basolateral membrane of ATII cells.

Adrenergic alpha-Agonists↗

PubMed2004

Swimming-induced pulmonary edema: clinical presentation and serial lung function.

BACKGROUND: Acute pulmonary edema has been noted in swimmers and divers, and has been termed swimming-induced pulmonary edema (SIPE). The mechanisms and consequences of SIPE are unknown, and there are currently no series of carefully evaluated patients with this condition. Herein we report the clinical presentation, incidence of recurrence, findings on physical examination, chest radiography, and oxygen saturation in 70 trainees with a diagnosis of SIPE. We also report the results of forced spirometry in a subgroup of 37 swimmers. METHODS: SIPE was diagnosed when severe shortness of breath and cough were reported during or after swimming, and were associated with evidence of pulmonary edema. During the years from 1998 to 2001, 70 cases of SIPE were documented in young healthy male subjects participating in a fitness-training program. Physical examination and pulse oximetry were performed immediately. Chest radiographs were obtained in all cases 12 to 18 h following onset of symptoms. In 37 swimmers, spirometry was performed at the time of chest radiography and again after 7 days. RESULTS: All subjects complained of severe shortness of breath. Sixty-seven of the 70 subjects (95.7%) had a prominent cough; in 63 subjects (90%), there was significant sputum production. Hemoptysis was observed in 39 subjects (55.7%). Mean arterial oxygen saturation after swimming was 88.4 +/- 6.6% breathing air, compared with 98 +/- 1.7% breathing air at rest before the start of the swimming trial (mean +/- SD) [p < 0.001]. Chest radiographs obtained 12 to 18 h after swimming were normal in all cases. Sixteen trainees (22.9%) had a recurrence of SIPE. Spirometry demonstrated restrictive lung function, which persisted for a week. CONCLUSIONS: In our trainee population, SIPE is a not uncommon, often recurrent phenomenon that significantly influences performance. It is not clear what predisposes to its occurrence or recurrence and what, if any, are its long-term effects.

Adolescent↗

PubMed2003

Augmentation of endogenous dopamine production increases lung liquid clearance.

We have previously reported that dopamine increased active Na+ transport in rat lungs by upregulating the alveolar epithelial Na,K-ATPase. Here we tested whether alveolar epithelial cells produce dopamine and whether increasing endogenous dopamine production by feeding rats a 4% tyrosine diet (TSD) would increase lung liquid clearance. Alveolar Type II cells express the enzyme aromatic-L-amino acid decarboxylase (AADC) and, when incubated with the dopamine precursor, 3-hydroxy-L-tyrosine (L-dopa), produce dopamine. Rats fed TSD, a precursor of L-dopa and dopamine, had increased urinary dopamine levels, which were inhibited by benserazide, an inhibitor of AADC. Rats fed TSD for 15, 24, and 48 hours had a 26, 46, and 45% increase in lung liquid clearance, respectively, as compared with controls. Also, dopaminergic D1 receptor antagonist--but not dopaminergic D2 receptor antagonist--inhibited the TSD-mediated increase in lung liquid clearance. Alveolar Type II cells isolated from the lungs of rats after they had been fed TSD for 24 hours demonstrated increased protein abundance of Na,K-ATPase alpha1 and beta1 subunits. Basolateral membranes isolated from peripheral lung tissue of tyrosine-fed rats had increased Na,K-ATPase activity and Na,K-ATPase alpha1 subunit. These data provide the first evidence that alveolar epithelial cells produce dopamine and that increasing endogenous dopamine increases lung liquid clearance.

Animals↗

PubMed2003

Leukotriene D4 activates alveolar epithelial Na,K-ATPase and increases alveolar fluid clearance.

Cysteinyl leukotrienes are increased during acute lung injury in animals and humans. In this study, we determined the effect of leukotriene D4 (LTD4) on the function of Na,K-ATPase in alveolar epithelial cells and on alveolar fluid clearance in rat lungs. LTD4 (1 x 10(-7) M) increased Na,K-ATPase activity at 1 and 5 minutes by 14% (p < 0.05) and 31% (p < 0.001), respectively, in A549 alveolar epithelial cells. This was accompanied by recruitment of Na,K-ATPase alpha1 subunits from intracellular compartment(s) to the basolateral plasma membrane. LTD4-induced alpha1 Na,K-ATPase membrane translocation was blocked by the dual cysteinyl LT1 (cysLT1)/ cysteinyl LT3 (cysLT3) receptor antagonist BAY-u9773, but not by the cysLT1 antagonist MK571, implicating the cysLT3 receptor. Expression of mRNA for cysLT2, but not cysLT1, was confirmed in A549 cells and rat alveolar type 2 cells by reverse transcriptase-polymerase chain reaction. Finally, compared with control, LTD4 (1 x 10(-11) M) increased alveolar fluid clearance by 41% (p < 0.001) in isolated, perfused rat lungs; this was also blocked by BAY-u9773 but not MK571. By activating alveolar epithelial Na,K-ATPase and increasing alveolar fluid reabsorption, cysteinyl leukotrienes may, in part, have a beneficial role in the acute respiratory distress syndrome.

Animals↗

PubMed2003

Na,K-ATPase gene transfer increases liquid clearance during ventilation-induced lung injury.

Mechanical ventilation with high tidal volumes (HVT) downregulates alveolar Na,K-ATPase function and impairs lung liquid clearance. We hypothesized that overexpression of Na,K-ATPase in the alveolar epithelium could counterbalance these changes and increase clearance in a rat model of mild ventilation-induced lung injury. We used a surfactant-based system to deliver 4 x 10(9) plaque-forming units of E1a-/E3- recombinant adenovirus containing either a rat beta1 Na,K-ATPase subunit cDNA (adbeta1) or no cDNA (adnull) to rat lungs 7 days before ventilation with a VT of approximately 40 ml/kg (peak airway pressure of less than 35 cm H2O) for 40 minutes. Lung liquid clearance and Na, K-ATPase activity and protein abundance were increased in HVT adbeta1-infected lungs as compared with sham and adnull-infected HVT lungs. These results suggest that Na,K-ATPase subunit gene overexpression in the alveolar epithelium increases Na,K-ATPase function and lung liquid clearance in a model of HVT. We provide here the first evidence that using a genetic approach improves active Na+ transport and thus liquid clearance in the setting of mild ventilation-induced lung injury.

Animals↗