Effects of antioxidant state on individual susceptibility to silicosis (an experimental study)

The authors proved that animals having higher natural antioxidant activity and lower intensity of lipid peroxidation are more resistant to fibrogenic effects of quartz. The peritoneal macrophages obtained from those animals show higher resistance to quartz exposure "in vitro". Parameters characterizing antioxidant system should be included into a group of indexes describing propensity to silicosis.     

Subchronic inhalation toxicity study of a water-dispersible polyester in rats

AQ55 is a high molecular weight, water-dispersible, amorphous polyester used in applications where the exclusion of solvents and conventional surfactants is desirable, such as water-based adhesives, coatings, emulsions, paint primers, cosmetics and detergents. Potential health effects were evaluated in rats exposed by inhalation for about 13 wk to mean concentrations of 0, 2.4, 19.6 or 199 mg/m3 AQ55 polymer. No mortality occurred and body weights were unaffected. Mean relative liver weights in all treated male groups were slightly higher than control weights, but were not judged to be treatment related. Absolute liver weights and all other organ weights except lung weights were normal. Haematology, clinical chemistries and gross pathology were unremarkable. Exposure-related changes in the 199 mg/m3 groups included increased mean absolute and relative lung weights, accumulations of macrophages and acute inflammatory cells in alveolar and bronchial lumina, and increased numbers of macrophages in sinusoids of peribronchial lymph nodes. Minor accumulation of macrophages in alveolar lumina was the only exposure-related change in the 19.6 mg/m3 group. No exposure-related effects were seen in the 2.4 mg/m3 group. AQ55 produced no systemic toxicity, and aerosols of AQ55 do not appear to be toxic to pulmonary tissues following subchronic inhalation exposure.     

Effects of cemented tungsten carbide dust on rat lungs following intratracheal injection of saline suspension

In order to examine the effect of cemented tungsten carbide dust on the animal lung, saline suspensions were intratracheally administered into the lungs of rats in a single dosage. About one-fifth of the animals died during the first three days. The acute response of the lungs was hemorrhagic edema with intense alveolar congestion. The animals killed at six months all presented pulmonary lesions of patchy fibrosis in the vicinity of the deposited dusts, occasionally associated with focal traction emphysema and bronchobronchiolar ectasia. At twelve months, two-third of the animals had neither fibrosis nor dust deposition, although the remaining animals showed pulmonary lesions similar to those seen in the six-months responders. Fibrosis of the lungs seemed to consist of collapsed alveoli with condensation of the preexistent reticulin fibers, but without noticeable collagenization. It is supposed that both the early toxic and the late fibrogenic effects of the carbide dust are attributable to the cytotoxic action of cobalt present in the dust particles. It is possible that recovery of the pulmonary lesions results from removal of the dusts from the lesions.     

Effects of methylphenidate on spatial working memory and planning in healthy young adults

Inhalation of cadmium oxide (CdO) is a significant form of human exposure to cadmium (Cd). Furthermore, there is epidemiological and experimental data relating Cd inhalation with lung cancer. Animal studies indicate that rats are more susceptible to Cd-induced lung cancer than mice, but interstrain sensitivity differences to Cd-induced pulmonary inflammation or carcinogenesis have not been addressed in either species. We compared pulmonary inflammatory processes in Wistar Furth (WF) rats with those in C57 and DBA mice exposed to freshly generated CdO fumes in nose-only inhalation chambers. Animals were exposed to 1 mg Cd/m3 for 3 hr and terminated immediately or 1, 3, and 5 days after exposure. Control animals were exposed to air/argon furnace gases. Cd-induced lung injury was assessed by bronchoalveolar lavage fluid (BALF) analyses, histopathology, and immunohistochemical detection of cell proliferation. Inhalation of CdO resulted in pulmonary inflammatory processes that varied widely across species and strains. C57 mice responded with faster and greater influx of neutrophils and proliferation of alveolar macrophages, type II epithelial cells, and bronchiolar epithelial cells compared to DBA mice or WF rats. DBA mice retained a greater percentage of inhaled Cd in the lungs and presented higher levels of BALF protein than C57 mice or rats. In comparison to mice, WF rats responded with a more transient inflammatory response in BALF parameters and higher degree of acute inflammation in lung tissue. The more pronounced proliferation of alveolar and bronchiolar epithelial cells observed in C57 mice might indicate higher susceptibility of this mice strain to Cd-induced lung carcinogenesis compared to DBA mice or WF rats. Furthermore, the present results of fewer inflammatory cells and lower proliferation of epithelial cells in DBA mice in association with our previous observation of higher Cd-induced metallothionein protein in this strain suggest that DBA might be less susceptible to the pulmonary carcinogenic effects of inhaled Cd than C57 mice or WF rats. We conclude that mice might not necessarily be more resistant than rats to the carcinogenic effects of inhaled Cd, since intraspecies susceptibility differences are strongly suggested by the present data. An extrapolation of this conclusion is that genetic variations in the human population may determine individual sensitivity differences to inhaled Cd.     

Benign tumors of the liver: primum non nocere

PURPOSE: This study evaluates the haemodynamic effects of oxygen inhalation on pulmonary artery pressure and pulmonary vascular resistance in patients with chronic thromboembolic pulmonary hypertension. METHOD: In 47 patients with chronic thromboembolic pulmonary hypertension haemodynamic parameters were measured before and after oxygen inhalation. RESULTS: In moderately severe and severe pulmonary hypertension oxygen inhalation significantly reduced mean pulmonary artery pressure by about 11.1% and 4.6%, respectively. However, pulmonary vascular resistance was not significantly affected. Oxygen saturation improved and heart rate was reduced. Cardiac index decreased in severe pulmonary hypertension. Systemic vascular resistance increased. CONCLUSION: We conclude that oxygen inhalation reduces pulmonary artery pressure and improves oxygen supply in patients with moderately severe and severe chronic thromboembolic pulmonary hypertension.     

Steroid sulphotransferase and 17beta-hydroxysteroid dehydrogenase activities in Ishikawa human endometrial adenocarcinoma cells

In 20 rats bronchitis was evoked by permanent 12-week long inhalation of SO2. For this purpose a special chamber with gas supply was prepared. In all rats exposed to SO2 changes in cellularity of BALF were found (a statistically significant increase of the percent of macrophages and neutrophils). Histologic examination revealed bronchial changes especially in epithelium. The method applied, based on an original technology is cheap and effective and can be recommended in developing experimental bronchitis.     

Enhanced hemodynamic response to [D-ALA2,D-MET5]-methionine enkephalin (DAME) in streptozotocin-induced diabetic rats is reversed by insulin replacement

The present study examined the alterations of hemodynamic responses to [D-ala2,D-Met5]-methionine enkephalin (DAME) in diabetic animals. Male Sprague-Dawley rats (12 weeks old) were used for this study. Diabetes was induced by a single injection of streptozotocin (65 mg/kg, i.v.). After 7 days, blood glucose levels were determined to confirm the diabetic state. Animals were anesthetized and instrumented to monitor mean arterial pressure, hindlimb bloodflow and hindlimb vascular resistance. Administration of DAME produced a significantly greater reduction in blood pressure, increase in hindlimb bloodflow and decrease in hindlimb vascular resistance in diabetic vs. control rats. These effects were blocked by naloxone. All hemodynamic changes were attenuated after pretreatment with the ganglionic blocker, hexamethonium, indicating that the responses were mediated either within the central nervous system or at the ganglia. Insulin reversed the exaggerated depressor effect of DAME on streptozotocin-treated rats. Collectively, these results suggest that diabetic rats have altered opioidergic hemodynamic responses to DAME due to mu receptor alterations in the CNS or in autonomic ganglia. These effects were reversed by replacement of insulin.     

Phosphodiesterase isoforms in the pulmonary arterial circulation of the rat: changes in pulmonary hypertension

Phosphodiesterase (PDE) activity was determined in pulmonary arteries removed from control and chronic hypoxia-induced pulmonary hypertensive rats. The main, first-branch, intrapulmonary and resistance pulmonary arteries were studied. We measured total cAMP PDE activity and cGMP PDE activity, as well as that of individual isoforms (PDE1-5). cAMP PDE activity in chronic hypoxic rats was increased in first-branch and intrapulmonary arteries from hypoxic rats. No changes were observed in the main or resistance pulmonary arteries. Similarly, cGMP PDE activity was increased in the main, first-branch and intra-pulmonary arteries of the hypoxic rats. No changes in cGMP PDE activity were observed in resistance arteries. There was evidence for PDE1-5 activity in all pulmonary arteries. The increased cAMP PDE activity in first-branch and intrapulmonary vessels was associated with an increase in cilostimide-inhibited PDE (PDE3) activity. Increased total cGMP PDE in main pulmonary artery was associated with increases in Ca++/calmodulin-stimulated (PDE1) activity. An increase in zaprinast-inhibited (PDE5) activity was observed in first-branch and intrapulmonary arteries. Our results suggest that decreases in intracellular cyclic nucleotide levels in pulmonary arteries from pulmonary hypertensive rats are associated with increased PDE activity. Further, these changes may reflect alterations at the level of specific types of PDE isoforms.     

Synthesis and expression of transforming growth factor-beta in activated macrophages

It has been established that once macrophages become activated, they pass through different stages of functional activity. Mouse macrophages activated by BCG "exerted" pronounced cytotoxic effects for 2-5 days to be followed later by growth-stimulating ones. However, in other experiments, the cytotoxic effect was either absent or occurred at later stages which was probably due to a certain functional state of macrophages before activation. The synthesis of TGF-beta increased 1-2 days after activation with BCG vaccine, lipopolysacharide and gamma radiation. An increase in mRNA TGF-beta i expression was observed only 5 days after activation of macrophages.     

The diagnosis of chronic dust-induced bronchitis

In dust-induced bronchitis, alterations in the pulmonary parenchyma present themselves in the main cellular indices for bronchioalveolar lavage (BAL), thought to be of much importance to its diagnosis. A total of 53 patients with initial and manifest forms of dust bronchitis underwent BAL. There has been found the following: a decrease in the mononuclear phagocyte system cells (MPhS) reflecting the state of local cellular immunity; rise in the amounts of coniophages, suggesting phagocytic activity of alveolar macrophages (AM) and dust blockade of MPhS cells; emergence and augmentation of counts of gigantic Pirogov-Langhans' cells characteristic of tuberculous granulomas, and also decrease in the counts of lymphocytes. There is a striking decrement in the vitality of AM, with polycytosis being commonly seen. Detection of granular forms of Mycobacterium tuberculosis in BAL and Pirogov-Langhans' cells enables a major proportion of "dust-induced bronchitis" to be considered as belonging to the silicotuberculous process.     

Psychiatric illness and family support in children and adolescents with diabetic ketoacidosis: a controlled study

BACKGROUND: In the adult respiratory distress syndrome, nitric oxide (NO) inhalation improves oxygenation through reducing ventilation-perfusion mismatching, but detailed information on the pulmonary effects of NO inhalation in septic shock is scarce. The present study investigated the effects of inhaled NO on alveolar dead space (Vdalv) and venous admixture as well as on respiratory system compliance (Crs) and respiratory system resistance (Rrs) in a porcine model of septic shock. Protective effects of NO are discussed. METHODS: Thirteen anaesthetised and ventilated pigs were given an infusion of endotoxin for an observation time of 220 min to induce acute lung injury (ALI). In the NO-early group (n=6), an inhalation of 60 ppm NO was started simultaneously with the endotoxin infusion and continued for 190 min. In 7 control/NO-late animals, 60 ppm NO was administered for 30 min following 190 min of endotoxin infusion. Haemodynamics, single-breath CO2-, pressure-, and flow signals were recorded. RESULTS: Endotoxin induced haemoconcentration, pulmonary vasoconstriction, and a decrease in Crs, while venous admixture, Vdalv, and Rrs increased. In the NO-early group, the pulmonary vasoconstriction was attenuated, no increase in pulmonary venous admixture or in Vdalv was seen before cessation of NO, and the improvements in oxygenation outlasted the NO inhalation. In the control/NO-late group, the NO inhalation reversed the changes in dead space and venous admixture. NO had no effect on the changes in respiratory mechanics. CONCLUSION: In porcine ALI, 60 ppm NO diminishes pulmonary vasoconstriction and improves gas exchange by reducing pulmonary venous admixture and alveolar dead space, but does not prevent a fall in Crs. NO inhalation may help prevent long-lasting pulmonary failure.     

Effects of magnetic field exposure on the development of lung fibrosis elicited by industrial pollutants

Lung injury elicited by a single intratracheal instillation of fibrogenic (quartz) and nuisance (anatase) dusts and/or weekly repeated instillation of CdCl2 solution combined with sinusoidal (50 Hz, 10 mT) magnetic field (MF) exposure was studied in male rats. Combined effects in bronchoalveolar lavage (BAL), rat lungs and regional lymph nodes after 4 months of MF exposure (1 h/5 days per week) were evaluated biochemically and by cytological and histopathological examination. Damage of cell membranes in the cell part of BAL due to MF exposure was not observed in the examined animal groups. Following MF exposure, decreased synthesis of collagen proteins (incorporation of [14C]proline) was demonstrated in lungs with quartz dust burden. Histological examination revealed differences in the lung tissue reaction suggesting the modification of the repair process due to MF exposure following experimental injury in both quartz and cadmium groups.     

The effect of inhaled nitric oxide on pulmonary ventilation-perfusion matching following smoke inhalation injury

BACKGROUND: We previously reported that inhaled nitric oxide (NO) improved pulmonary function following smoke inhalation. This study evaluates the physiologic mechanism by which inhaled NO improves pulmonary function in an ovine model. METHODS: Forty-eight hours following wood smoke exposure to produce a moderate inhalation injury, 12 animals were anesthetized and mechanically ventilated (FIO2, 0.40; tidal volume, 15 mL/kg; PEEP, 5 cm H2O) for 3 hours. For the first and third hours, each animal was ventilated without NO: for the second hour, all animals were ventilated with 40 ppm NO. Cardiopulmonary variables and blood gases were measured every 30 minutes. The multiple inert gas elimination technique (MIGET) was performed during the latter 30 minutes of each hour. The data were analyzed by ANOVA. RESULTS: Pulmonary arterial hypertension and hypoxemia following smoke inhalation were significantly attenuated by inhaled NO compared with the values without NO (p < 0.05, ANOVA). Smoke inhalation resulted in a significant increase in blood flow distribution to low VA/Q areas (VA/Q < 0.10) with increased VA/Q dispersion. These changes were only partially attenuated by the use of inhaled NO. The SF6 (sulfur hexafluoride) retention ratio was also decreased by inhaled NO. Peak inspiratory pressures and pulmonary resistance values were not affected by inhaled NO. CONCLUSIONS: Inhaled NO moderately improved VA/Q mismatching following smoke inhalation by causing selective pulmonary vasodilation of ventilated areas in the absence of bronchodilation. This modest effect appears to be limited by the severe inflammatory changes that occur as a consequence of smoke exposure.     

Continuous inhalation of small amounts of formaldehyde: experimental study in the rat

The results of experiments on the Rat, about the effects of continuous inhalation of 1.60, 4.55 and 8,07 ppm of formaldehyde, are reported: 150 SPF male rats were observed during one and an half to three months. These experiments concerned the clinical observation of the rats, their body weight and food intake, the relative weights of their lungs, liver, kidneys and spleen, the number and activity of their alveolar macrophages harvested by pulmonary washing. 1degree At 1.60 ppm it was only observed a yellowing of the hair of the intoxicated rats. 2degrees At 4.55 ppm, besides, the body weight of the intoxicated animals became significantly lower than the controls. 3degrees At 8.07 ppm, in addition to those differences, it appeared signs of irritation in the upper respiratory tract and in the eyes of the intoxicated rats, a significant underfeeding and a percentage of liver weight lower than the controls. Besides, the relative number and the phagocytic ability of alveolar macrophages of intoxicated rats was significantly lower than the controls. It was not observed the phenomena of adaptation previously described in the experimental rat intoxication by acrolein.     

The effect of splenectomy on alveolar macrophages morphology and function

OBJECTIVE: To study the morphological and functional changes of pulmonary alveolar macrophages of rats after splenectomy, and the applied effects of splenic tissue autotransplantation in practice. METHODS: 87 Wistar rats were randomly divided into shamoperation group, splenectomy group and splenic tissue autotransplantation group. Six months after splenectomy, alveolar macrophges were subjected to brochoalveolar lavage described by Shennib. The dynamic survival and adherent rate of alveolar macrophages in culture, lysosomal enzyme content, hydrogen peroxide production and expression level of interleukin 1 (IL-1) activity of alveolar macrophages were quantitatively measured. The alveolar macrophages ultrastructure was observed by utilizing transmission electron microscope. RESULTS: The splenectomized rat's alveolar macrophages were different from alveolar macrophages of sham-operated rats. Their surface filopodia was reduced and shortened, lysosome fewer and its acid phosphatase quantity decreased, adherence postponed, hydrogen peroxide production and expression of IL-1 activity impaired. Splenic tissue autotransplantation fairly restored the splenic effects on maturation and function of alveolar macrophages. CONCLUSION: Splenic tissue autotransplantation is a simple useful operation for preserving splenic function after splenectomy.     

Particle clearance and histopathology in lungs of F344/N rats and B6C3F1 mice inhaling nickel oxide or nickel sulfate

The goals of this study were to (1) determine the effects of repeated inhalation of relatively insoluble nickel oxide (NiO) and highly soluble nickel sulfate hexahydrate (NiSO4.6H2O) on lung particle clearance, (2) investigate the effects of repeated inhalation of NiO or NiSO4 on the pulmonary clearance of subsequently inhaled 85Sr-labeled microspheres, (3) correlate the observed effects on clearance with accumulated Ni lung burden and associated pathological changes in the lung, and (4) compare responses in F344 rats and B6C3F1 mice. Male F344/N rats and B6C3F1 mice were exposed whole-body to either NiO or NiSO4.6H2O 6 hr/day, 5 days/week for up to 6 months. NiO exposure concentrations were 0, 0.62, and 2.5 mg NiO/m3 for rats and 0, 1.25, and 5.0 mg NiO/m3 for mice. NiSO4.6H2O exposure concentrations were 0, 0.12, and 0.5 mg NiSO4.6H2O/m3 for rats and 0, 0.25, and 1.0 mg NiSO4.6H2O/m3 for mice. After 2 and 6 months of whole-body exposure, groups of rats and mice were acutely exposed nose-only to 63NiO (NiO-exposed animals only), 63NiSO4.6H2O (NiSO4.6H2O-exposed animals only), or to 85Sr-labeled polystyrene latex (PSL) microspheres (both NiO- and NiSO4.6H2O-exposed animals) to evaluate lung clearance. In addition, groups of rats and mice were euthanized after 2 and 6 months of exposure and at 2 and 4 months after the whole-body exposures were completed to evaluate histopathological changes in the left lung and to quantitate Ni in the right lung. Repeated inhalation of NiO results in accumulation of Ni in lungs of both rats and mice, but to a greater extent in lungs of rats. During the 4 months after the end of the whole-body exposures, some clearance of the accumulated Ni burden occurred from the lungs of rats and mice exposed to the lower, but not the higher NiO exposure concentrations. Clearance of acutely inhaled 63NiO was also impaired in both rats and mice, with the extent of impairment related to both exposure concentration and duration. However, the clearance of acutely inhaled 85Sr PSL microspheres was not impaired. The repeated inhalation of NiO resulted in alveolar macrophage (AM) hyperplasia with accumulation of NiO particles in both rats and mice, chronic alveolitis in rats, and interstitial pneumonia in mice. These lesions persisted throughout the 4-month recovery period after the NiO whole-body exposures were terminated. In contrast, repeated inhalation of NiSO4.6H2O did not result in accumulation of Ni in lungs of either rats or mice and did not affect the clearance of 63NiSO4.6H2O inhaled after either 2 or 6 months of NiSO4.6H2O exposure. Clearance of the 85Sr-labeled microspheres was significantly impaired only in rats exposed to the microspheres after 2 months of exposure to NiSO4.6H2O. Histopathological changes in rats were qualitatively similar to those seen in NiO-exposed rats. Only minimal histopathological changes were observed in NiSO4.6H2O-exposed mice. These results suggest that repeated inhalation of NiO at levels resulting in AM hyperplasia and alveolitis may impair clearance of subsequently inhaled NiO. The potential effects of repeated inhalation of soluble NiSO4.6H2O on the clearance of subsequently inhaled poorly soluble particles are less clear.     

Riluzole interacts with voltage-activated sodium and potassium currents in cultured rat cortical neurons

Inhaled nitric oxide is a selective pulmonary vasodilator used for the treatment of pulmonary hypertension. The potential adverse effects of inhaled nitric oxide are unknown and represent the focus of the present studies. Whereas inhalation of nitric oxide (10 to 100 ppm, 5 h) by Balb/c mice had no effect on the number or type of cells recovered from the lung, a dose-related increase in bronchoalveolar lavage protein was observed, suggesting that nitric oxide induces alveolar epithelial injury. To determine if this was associated with altered alveolar macrophage activity, we quantified production of reactive oxygen and nitrogen intermediates by these cells. Interferon-gamma, alone or in combination with lipopolysaccharide (LPS), induced expression of inducible nitric oxide synthase (iNOS) protein and nitric oxide production by alveolar macrophages. Cells from mice exposed to 20 to 100 ppm nitric oxide produced significantly more nitric oxide and expressed greater quantities of iNOS than cells from control animals. Superoxide anion production and peroxynitrite generation by alveolar macrophages were also increased after exposure of mice to nitric oxide. This was correlated with increased antinitrotyrosine antibody binding to macrophages in histologic sections. Taken together, these data demonstrate that inhaled nitric oxide primes lung macrophages to release reactive oxygen and nitrogen intermediates. Increased production of these mediators by macrophages following inhalation of nitric oxide may contribute to tissue injury.     

Nutritional practices of elite female surfers during training and competition

Inhaled beryllium (Be) can induce a range of adverse pulmonary responses in animals and humans including acute pneumonitis, chronic granulomatous lung disease, and cancer. To facilitate comparisons with our previous data describing Be toxicity in rats, we evaluated the toxic effects of inhaled Be metal in mice. Groups of 34 strain C3H/HeJ mice were acutely exposed by the nose-only route to aerosolized Be metal to achieve measured initial lung burdens of 0, 1.7, 2.6, 12, or 34 microg. All mice received aerosolized 85 Sr-labeled fused aluminosilicate particles (85 Sr-FAPs) immediately before their Be exposure so that the influence of Be on lung retention of these poorly soluble tracer particles could be externally quantitated. Groups of mice were euthanized at 8, 15, 40, 90, 210, and 350 days after exposure for evaluation of histopathological changes and for cytologic and biochemical indicators of lung damage measured in bronchoalveolar lavage fluid. Clearance of 85 Sr-FAP tracer particles through 196 days after exposure was delayed in mice receiving the 12 and 34 microg Be lung burdens, but not the 1.7 or 2.6 microg lung burdens. Increased total cell numbers, increased percentage of neutrophils, and elevated levels of total protein and the activities of beta-glucuronidase and lactate dehydrogenase in bronchoalveolar lavage fluid were observed in the two highest Be lung burden groups compared with controls. Lung lesions included particle-containing macrophages, granulomatous pneumonia, lymphocytic interstitial aggregates, and mononuclear interstitial infiltrates. These lesions were occasionally seen in mice receiving the 2.6 microg lung burden, were present in most of the mice receiving 12 or 34 microg lung burdens, and were generally increased in severity with time and lung burden. Thus, we have demonstrated that a single, acute inhalation exposure to Be metal can chronically retard particle clearance and induce lung damage in mice. The initial lung burdens used caused responses ranging from no apparent effects to significant Be-induced responses. A comparison of these data with our previous data from rats indicates that the mass of Be metal required to induce lung damage in mice is similar to that needed for rats. When expressed on a lung weight-normalized basis, mice appeared to be more resistant to the toxic effects of inhaled Be than rats.     

Effect of phenytoin on smoke inhalation injury in sheep

To determine whether the anti-inflammatory effects of phenytoin might reduce cardiopulmonary dysfunction we studied the effects of phenytoin treatment on acute lung injury induced by smoke inhalation. Twenty-one chronically instrumented sheep were observed for 24 h after smoke inhalation injury. Myocardial contractility was evaluated by left ventricular end-systolic pressure-diameter relationship (LVESPDR) with a pair of ultrasonic transducers and strain-gauge transducer. In the control group (n = 6), uninjured sheep were given a bolus of phenytoin (12.5 mg/kg). Smoke-insufflated sheep were divided into nontreatment (n = 7) and phenytoin (n = 8) groups. Phenytoin alone had no effects in uninjured sheep except an early rise in heart rate and LVESPDR. In the group given smoke without treatment, there was a significant increase in pulmonary artery pressure and pulmonary vascular resistance index and a decrease in cardiac index. Pulmonary vascular changes were attenuated by treatment with phenytoin. Pulmonary transvascular fluid flux was evaluated by using a lung lymph fistula. LVESPDR fell in the smoke group but not in the group given phenytoin. There was a marked increase in lung lymph flow with smoke inhalation but this phenomenon was not affected by phenytoin treatment. In conclusion, phenytoin treatment reduced early hemodynamic depression.