[Bevacizumab and lung cancer: eligible patients in daily practice]. / Bévacizumab et cancer bronchique: population cible en pratique quotidienne.

BACKGROUND: Combining bevacizumab with platinum-based chemotherapy significantly improves survival for patients with advanced non-squamous non-small cell lung cancer. The objective of this study was to assess the proportion of patients who could receive this combined therapy. METHODS: This was a retrospective single centre analysis of patients treated between 2007 and 2008. Exclusion criteria for bevacizumab included: squamous cell carcinoma, contraindication to platinum-based chemotherapy, uncontrolled hypertension, haemoptysis superior to 2.5 mL, recent surgery, and/or tomodensitometric criteria after independent review by two radiologists (contact with a proximal vessel, tracheobronchial involvement, cavitation). Cardiovascular diseases and central tumour location were not systematically considered as contraindications. RESULTS: Among 194 patients analysed, 21 (10.8%) to 35 (18%) patients were eligible for bevacizumab, whether or not cardiovascular diseases and central tumour location were considered as contraindications. The kappa coefficient was 0.49. CONCLUSION: Even though the proportion of patients who can receive chemotherapy plus bevacizumab may vary according to the eligibility criteria chosen and the interpretation of the CT scan, it is unlikely to exceed 25% of patients in daily practice.

Influence of buffered propionic acid on the development of micro-organisms in hay.

We tested the benefit of using buffered propionic acid (BPA) as a means of preventing farmer's lung disease (FLD). BPA, a new formulation of propionic acid, a hay preservative with no deleterious effect on farm machinery or cattle, reduces the development of micro-organisms in hay. Twenty pairs of round bales were analysed for concentration of micro-organisms measured in the winter following hay treatment. Each pair included one untreated bale and one bale treated with BPA during haymaking. Our results showed the following decreases in concentration in treated bales: total fungal species, 40% (P < 0.05); Eurotium amstelodami (the main species found), 65% (P < 0.01); and thermophilic actinomycetes, 60% (not significant), respectively. We conclude that BPA could be used to prevent FLD.

[Repetitive acute pancreatitis in a late-diagnosed cystic fibrosis: prevention of relapses by octreotide in the long term]. / Poussées à répétition de pancréatite aiguë dans une mucoviscidose à révélation tardive: prévention par octréotide au long cours.

We report on the case of a 35 year-old woman who was initially admitted for acute pancreatitis in october 1995. The patient was suffering from asthma (since childhood) and diffuse abdominal pain (since adolescence). The diagnosis of cystic fibrosis was made fortuitously during a sterility evaluation. After extensive etiological screening the acute pancreatitis was considered to be a manifestation of the cystic fibrosis. Despite therapy with pancreatic enzymes, the patient continued to suffer from chronic abdominal pain. High intake of analgesics was required. Until December 1995, the patient was repeatedly admitted for episodes of acute pancreatitis. In January 1996, we initiated a preventive treatment with subcutaneous octreotide between 100 and 200 microgram, three time a day. Thereafter, there were fewer episodes of pancreatitis and the consumption of analgesics decreased. Side effects of octreotide were intermittent diarrhea and development of cholelithiasis that was complicated by biliary migration in November 1998. In June 1999, the prolonged-release form of the molecule was given without modification of the efficacy.

Efficacy and tolerance of a new silicone stent for the treatment of benign tracheal stenosis: preliminary results.

STUDY OBJECTIVE: In inoperable patients with tracheal stenosis who are treated using silicone stents, stent migration occurs in 18.6% of cases. To decrease the migration rate, we have designed a new silicone stent with narrow central and larger distal parts. This study analyzes the stability and tolerance of this new stent. DESIGN: Preliminary prospective study conducted in two French university hospitals. PATIENTS: Thirteen inoperable patients with benign complex tracheal stenosis due to intubation or tracheotomy. INTERVENTIONS: Tracheal stent insertion was performed under general anesthesia with a rigid bronchoscope. The patients were followed up clinically up to stent removal, which was planned at 18 months. RESULTS: Stent insertion or removal was very simple and did not differ from other silicone stents. No migration occurred after a mean follow-up of 22.8 months. Minimal granuloma formation occurred in only one patient (7.7%). Sputum retention remained similar to that with other silicone stents and could be improved by a smoother internal wall. Stents have been removed in seven patients after a mean duration of 19.6 months, with a complete stenosis cure in four cases. CONCLUSION: This new stent combines the excellent stability of the metallic stents and the tolerance and easy removal of straight silicone stents. This allows a prolonged use in order to obtain curative action.

Relationships of immunoglobulins E and G sensitization to respiratory function in dairy farmers.

An impairment of respiratory function has been demonstrated in dairy farmers. The objective of this study was to evaluate the relationship of allergy to respiratory function in dairy farmers in a longitudinal study conducted in the Doubs (France). A cohort of male dairy farmers constituted in 1990 was re-evalued in 1995. Subjects completed a medical and occupational questionnaire, and a spirometry test in both 1990 and 1995, in 1995 they were also subjected to immunological tests. Relationships between immunological variables and respiratory function were studied by a multiple linear regression model adjusted for age, smoking status, respiratory symptoms, altitude and occupational exposure. Amongst the 394 subjects of the initial cohort, 330 were included in the longitudinal study and 320 had immunological tests. Log immunoglobulin (Ig) E was negatively correlated with the 1995 respiratory function parameters (p<0.05 for forced expiratory volume in one second (FEV1) and FEV1/vital capacity (VC). Immunoglobulin (Ig) G response to Aspergillus fumigatus detected by enzyme-linked immunosorbent assay (ELISA) was negatively correlated to 1995 respiratory function parameters (VC: p<0.01; FEV1: p<0.001; FEV1/VC: p<0.01). There was a positive relationship between IgG antibodies against Aspergillus fumigatus and the mean annual decline in FEV1 (p<0.01) and FEV1/VC (p<0.01). To conclude, allergy may play a role in the impairment of respiratory function in dairy farmers of the Doubs and sensitization to Aspergillus fumigatus seems to constitute an independent risk factor for the development of airflow obstruction in this occupational setting.

Prevalence of asthma and respiratory symptoms in dairy farmers in the French province of the Doubs.

With the aim of determining whether dairy farming is associated with an excess of asthma and respiratory symptoms, we compared the respiratory status in a sample of dairy farmers (n = 265) and a control group of nonexposed subjects (n = 149). The study protocol comprised a questionnaire, spirometry, and a bronchodilatation test (400 micrograms salbutamol powder), and an allergological evaluation: serum total IgE level, Phadiatop test, and skin prick tests (SPT) for seven inhalant allergens. Cumulative prevalences of self-reported asthma and of current asthma were respectively 5.3% and 1.5% in farmers, and respectively 3.4% and 1.3% in control subjects (both NS). Prevalences of all the respiratory symptoms studied were higher in farmers, with statistically significant differences after adjusting for age, sex, and smoking, for wheezing ever (OR: 2.7, p < 0.05), wheezing within the last year (OR: 5.2, p < 0.025), usual morning cough (OR: 5, p < 10(-)3), usual morning phlegm (OR: 11.3, p < 10(-)4), and chronic bronchitis (OR: 11.8, p < 0.01). The effect of exposure on these symptoms was more pronounced than, or of the same magnitude as that of smoking. Smoking and exposure had an additive effect except for chronic cough for which a positive interaction was observed (p = 0.05). Mean FEV1/VC (percentage of predicted) was statistically negatively correlated to dairy farming (p < 0.025) after adjusting for confounders. Bronchial obstruction was reversible in about 10% of subjects in both groups. In conclusion, this study mainly demonstrated an excess of respiratory symptoms in dairy farmers which is weak and nonsignificant for asthma, and high for cough, phlegm, and chronic bronchitis. It also suggested that the combined effect of farming and smoking was synergistic on chronic cough.

Six year longitudinal study of respiratory function in dairy farmers in the Doubs province.

A previous study, carried out in 1986 in France, showed the prevalence of respiratory symptoms and of respiratory function impairment to be higher in dairy farmers than in a control group of nonexposed subjects living in a rural zone. In order to confirm the harmful effect of dairy farming, the two groups were re-studied 6 yrs later at the same period of the year. One hundred and ninety-four (77.6%) farmers and 155 (62%) control subjects were available for re-examination. Non-re-evaluated subjects were comparable to re-evaluated subjects for age, sex, smoking and respiratory symptoms and function at initial evaluation. Dairy farmers consistently had more respiratory symptoms and lower levels of respiratory function than did control subjects. In the study populations as a whole, the mean annual decline in vital capacity (VC) and forced expiratory volume in one second (FEV1) was slightly, but nonsignificantly, higher in farmers than in control subjects: in mL x yr(-1) (SD), -43.1 (68.2) versus -37.9 (60.2) for VC and -32.8 (56.7) versus -30 (47.2) for FEV1. There was a positive interaction between farming and age (i.e. duration of exposure in this cohort) on respiratory function decline, and in male subjects aged > or = 45 yrs, dairy farming was associated with an accelerated loss in VC (p<0.05) and FEV1 (p<0.05) after controlling for age, smoking, height and geographic location in a multiple linear regression model. Initial values of respiratory function, age and pack-years smoked (only for VC) were the other variables found to be significant determinants of decline in lung function. In conclusion, this study mainly suggests that dairy farming is associated to a very moderate accelerated loss in respiratory function that increases with duration of exposure and is significant in older male subjects.

[Respective influence of occupational and personal factors on respiratory function in dairy farmers]. / Influence respective des facteurs professionnels et personnels sur la fonction respiratoire en milieu agricole de production laitière.

Occupational and individual factors influencing respiratory function were analysed in a sample of dairy farmers. The study protocol included a medical questionnaire, an occupational questionnaire, spirometry and allergological tests (skin prick tests for a panel of inhalant allergens, serum total IgE level and Phadiatop (CAP System). Two hundred and forty-five farmers were studied (140 men, 105 women with an average age of 45.9 (11.3) years, 35 were smokers, 27 ex-smokers and 183 non-smokers). A multiple linear regression model was used to analyse the correlations between respiratory function and the different independent variables. There was a statistically significant negative correlations between smoking (expressed in pack-years) and all the respiratory function parameters (p < 0.01). Respiratory function was significantly impaired in farmers working on traditional farms (p < 0.05 for VC and for FEV1), and the respiratory function values increased proportionally with the modernisation of the farms (notably using an artificial barn drying system for hay and a ventilation system for the cow byres). No significant relationship between respiratory function and quantitative indicators of exposure (size of farm, amount of livestock, quantity of hay handled during professional lifetime) or indicators of IgE-mediated allergy was observed. In conclusion, this study suggests that traditional work conditions in farms which have little mechanisation are, along with tobacco, the determining factors for the respiratory function impairment in dairy farmers.

Use of the 25 mm flanged esophageal Z stent for malignant dysphagia: a prospective multicenter trial.

BACKGROUND: An initial multicenter study using a 21 mm flanged esophageal Z stent demonstrated excellent palliation but an 11% immediate complication rate at placement and a 27% migration rate at 1 month. This North American multicenter trial prospectively studied a 25 mm flanged Z stent to define its palliative ability and whether the increased diameter affected placement or migration problems. METHODS: Fifty patients who had esophageal Z stents at seven university or regional referral hospitals were prospectively studied. Indications for prosthesis placement, previous therapy, patient demographics, incidence of concomitant tracheoesophageal fistula, and degree of dysphagia were defined, as were procedural and subsequent stent-related problems, survival times, the ability to occlude a tracheoesophageal fistula, and subsequent degree of dysphagia. RESULTS: Twenty-four patients had infiltrating malignancy (16 exophytic and 10 extrinsic), 9 of whom had concomitant tracheoesophageal fistulas. Ten patients (20%) had misplaced stents requiring retrieval and replacement, 12 patients (24%) had subsequent stent-related problems including exsanguination (2), aspiration (3), tumor overgrowth (3), and postplacement migration (4) (8%). There was statistically significant improvement in prestent versus poststent dysphagia and two thirds of patients had complete occlusion of their tracheoesophageal fistula. CONCLUSIONS: Redesign of the esophageal Z stent has decreased the migration rate without increasing placement or subsequent erosion problems. Its efficacy appears comparable to the currently marketed Z stent for the palliation of malignant dysphagia and occlusion of tracheoesophageal fistula.

[Second line chemotherapy in patients with refractory and resistant non small cell lung cancer]. / Chimiothérapie de deuxième ligne chez les patients réfractaires et résistants atteints de cancers du poumon non à petites cellules.

Effectiveness of chemotherapy has been demonstrated in stage IV non small cell lung cancer as well as in stage IIIb disease when combined with radiotherapy. A significant improvement of both survival and quality of life was shown and is thought to be associated with higher efficiency. Therefore, treatment of relapses is now a question of practical interest. Ninety-seven non small cell lung cancer patients who were delivered a second line chemotherapy following primary chemotherapy alone were reviewed. Sixty-five patients were administered a 2 drug cisplatin-based regimen (with etoposide, bleomycin or vinorelbine). Twenty eight patients received no cisplatin but the cyclophosphamide, epirubicin combination or any 2-drug regimen assembled from the following agents: etoposide, mitomycin, ifosfamide. The last 4 patients were given single-agent vinorelbine. Fifteen objective responses (15.2%) (95% CI: 9-24%) were observed. The median response duration was 27 weeks. Response rates were 18.4% (95% CI 9-28%) and 9.3% (95% CI: 0-19%) in cisplatin-based combinations and in other regimens, respectively. No difference in response rates was observed between primary responsive and non responsive patients but response rates were influenced by the choice of the first line combination chemotherapy.

Longitudinal study of respiratory health in dairy farmers: influence of artificial barn fodder drying.

Factors influencing respiratory consequences of dairy farming have not been extensively investigated to date. To evaluate the effects of barn fodder drying on respiratory symptoms and lung function, a 5 yr follow-up study was performed in the Doubs (France). A cohort of male dairy farmers was analysed in 1990. The initial cross-sectional results suggested that barn-drying fodder may protect dairy farmers from lung function impairment. In 1995, 113 barn-drying farmers (92%) and 231 traditional-drying farmers (84%) were re-analysed. Barn and traditional fodder-drying farmers were compared for prevalence of symptoms and spirometric measures of lung function. After controlling for age, smoking status, altitude and cumulative exposure, barn-drying farmers compared to traditional-drying farmers had a lower prevalence of chronic bronchitis (4 versus 10%; p<0.05) and slightly higher values of forced expiratory volume in one second (FEV1) (p=0.06) and FEV1/vital capacity (VC) (p<0.01). Nevertheless, decline of the respiratory function parameters was not significantly different between the two groups. Variables positively and significantly associated to longitudinal decline of lung function parameters were: age (FEV1, FEV1/VC); altitude (VC, FEV1) and chronic bronchitis and dyspnoea at the initial survey (FEV1/VC). Persistence and emergence of chronic bronchitis, dyspnoea and symptoms at exposure were also significantly associated to an acceleration in the annual decline of the respiratory function. In conclusion, the mode of fodder drying does not seem to significantly influence the decline in lung function. Nevertheless, this study confirms the results of the initial cross-sectional analysis and supports the hypothesis that barn drying fodder may have a protective effect on respiratory health in dairy farming.

Rheumatoid arthritis and bronchiectasis. A retrospective study of fourteen cases.

Since 1928, 288 cases of rheumatoid arthritis and bronchiectasis have been reported in the medical literature. The interactions between these two conditions and the etiopathogenic mechanisms they involve remain unclear. During a retrospective study of 100 rheumatoid arthritis patients and 80 bronchiectasis patients, we identified 14 additional patients with both conditions. There were 10 females and four males (ratio 2.5/1). Bronchiectasis was confirmed either by computed tomography of the chest or by bronchography. The respiratory manifestations antedated the joint disease in 12 patients, by a mean interval of 28.5 years. An infectious cause was identified in six cases. Neither the age at onset nor the duration of rheumatoid arthritis were influenced by the presence of bronchiectasis. Seven patients had 15 extraarticular manifestations suggesting potentially severe joint disease. The flares of joint and respiratory symptoms were concomitant in six patients. In six patients, the respiratory manifestations worsened after onset of the joint disease. Tests for rheumatoid factors were positive in 73% of cases. Panhypogammaglobulinemia was found in one case. Ten patients underwent lung function tests, which showed evidence of nonspecific obstructive disease. Overall, our findings are consistent with previous reports in the literature. In patients with predisposing immunogenetic factors, bronchiectasis may be involved in the genesis of rheumatoid arthritis.

[Prevalence of immediate allergy to respiratory allergens in fodder farmers in Doubs]. / Prévalence de l'allergie immédiate aux pneumallergènes chez les agriculteurs fourragers du Doubs.

The Doubs is a damp, semi-mountainous fodder farming department in which occupational respiratory diseases (including asthma) are common in farmers. We studied the prevalence of IgE-mediated allergy (total IgE, Phadiatop and skin prick tests) in a group of 265 exclusive dairy farmers of both sexes of the department and in a control group of non exposed, administrative workers living in the same area. Skin prick tests were: Dermatophagoides pteronyssinus, Acarus siro, cat hair, cow danders, grass pollens, betullacea pollens (trees from the East of France), and hay extracts from the Doubs. Total IgE were higher than 180 KUI/l in 26 (9.9%) farmers and in 15 (10.5%) controls (NS). Phadiatop was positive in 41 (15.7%) farmers and in 27 (19%) controls (NS). Prevalence of positive skin prick tests (at least one) in farmers and controls was respectively 36% and 40% (NS). Farmers were more frequently sensitized to hay extracts (OR = 1.7), cow danders (OR = 1.3) and less frequently to cat hair (OR = 0.63) than controls but the differences were not statistically significant. In conclusion, this study fails to give evidence of a risk of IgE-mediated allergy to work-related and other common inhalation allergens in dairy farmers the Doubs.

Influence of barn drying of fodder on respiratory symptoms and function in dairy farmers of the Doubs region of France.

BACKGROUND: A previous study showed there to be fewer microorganisms (especially thermophilic actinomycetes) on farms with artificial barn drying of fodder than on those using traditional storage methods. A cross sectional study was performed to see whether barn drying provides protection against respiratory problems in dairy farmers. METHODS: The respiratory symptoms and function of a group of 123 farmers with daily exposure to cattle foddering from farms which had had a barn drying system for at least three years were compared with those of a representative sample of 274 farmers working in farms with traditional storage in five districts in the Doubs region of France. RESULTS: Both groups were comparable for mean age, weight, height, smoking habits, alcohol consumption, past history of respiratory disease, history of allergy, geographical location of the farm, and length of exposure. Retrospectively estimated exposure to fodder was greater in the group using a barn drying system than in the group working with traditional storage. Acute symptoms at exposure (rhinitis, eye irritation, dry cough, asthma symptoms) and chronic symptoms all tended to be less frequent in the barn drying group, although not individually significantly so. Mean (SD) respiratory function parameters were higher in the barn drying group than in the traditional group: % vital capacity (VC) 104 (14) v 102 (15); % forced expiratory volume in one second (FEV1) 99 (14) v 94 (18); % FEV1/VC 96 (11) v 92 (16); % forced mid expiratory flow (FEF25-75) 87 (24) v 79 (25). CONCLUSION: The results of this cross sectional study suggest that barn drying of fodder may protect respiratory function in dairy farmers.

Prevalence and risk factors for chronic bronchitis and farmer's lung in French dairy farmers.

The prevalence of chronic bronchitis and of clinical farmer's lung was studied in 30 districts of the French Doubs province in relation to individual (age, sex, smoking) and geographical (altitude) factors. 5703 exclusively dairy farmers (response rate 83%) participated in the study by answering a medical questionnaire. Prevalences of chronic bronchitis and clinical farmer's lung were 9.3% and 1.4% respectively. A logistic regression model was used to evaluate risk factors for chronic bronchitis and clinical farmer's lung. A risk of chronic bronchitis was associated with male sex (p < 10(-4)), age (p < 10(-4)), smoker category (p < 10(-4)), and altitude (p < 10(-4)). A risk of clinical farmer's lung was associated with non-smokers (p < 0.05), and linearly with altitude (p < 10(-4)). Also there was a strong positive relation between chronic bronchitis and clinical farmer's lung (odds ratio 19.5 (95% confidence interval 12.1-31.4) after adjustment for confounding variables. The main finding of this study is the highly significant increase of prevalence of the diseases in relation to altitude.

Cardiovascular hyporesponsiveness to norepinephrine, propranolol and nitroglycerin in portal-hypertensive and aged rats.

Most studies testing vasoactive agents in portal-hypertensive rats have been performed in young animals. To assess age-related changes in hemodynamic responses to adrenergic stimuli, we examined (a) responsiveness to norepinephrine (0.14 to 12.0 micrograms.kg-1.min-1) in young (3-mo-old) and aged (9-mo-old) sham-operated and portal-hypertensive rats and (b) response to propranolol (2 and 10 mg.kg-1 body wt), nitroglycerin (3.6 mg.kg-1.min-1) or saline solution in aged portal-hypertensive rats. Aged rats exhibited significantly (p < 0.05) smaller responses to norepinephrine with regard to increases in mean arterial pressure and superior mesenteric arterial vascular resistance, irrespective of portal hypertension. Portal hypertension alone potentiated this reduced response in aged animals and was associated with cardiovascular hyporesponsiveness to norepinephrine in young rats. Portal pressure was significantly (p < 0.05) lower in aged sham-operated rats than in young sham-operated rats over a wide range of norepinephrine doses. Portal-hypertensive aged rats showed significantly (p < 0.05) lower heart rates. Furthermore, systemic and splanchnic cardiovascular responses to propranolol and nitroglycerin mediated by the sympathetic nervous system were decreased or negligible in aged rats, compromising the portal-hypotensive effects of these drugs. In summary, aged rats express diminished cardiovascular responsiveness to adrenergic stimuli. Therefore age should be considered an important factor in studies evaluating pharmacological agents for the treatment of portal hypertension.

Pharmacological control of portal hypertension.

The initiation and maintenance of portal hypertension, development of portosystemic shunts, including esophagogastric varices, and precipitation of variceal hemorrhage result from a number of different although related hemodynamic variables. Knowledge of these pathophysiological mechanisms is essential for an understanding of the pharmacological therapy of portal hypertension. Conversely, pharmacological studies continue to provide new insights and expand our understanding of these pathophysiological mechanisms. Future pharmacological studies should contribute to our understanding of the role of endothelial-dependent and -independent mechanisms in the regulation of vascular tone in chronic liver disease, the regulation of intrahepatic resistance, and the development and modulation of the portocollateral vascular bed. Ideally, this will yield increasingly effective pharmacological therapies for the management of portal hypertension.

Influence of anesthesia, postanesthetic state, and restraint on superior mesenteric arterial flow in normal rats.

To exclude possible confounding effects of anesthesia on splanchnic hemodynamics, two different awake postanesthetic models (PAM), restrained and unrestrained, have been used. However critical analysis of the splanchnic hemodynamic state in these models is not available. We conducted experiments using chronically implanted pulsed-Doppler flow probes on the superior mesenteric artery (SMA) in ketamine-anesthetized and in postanesthetic restrained and unrestrained normal rats. Baseline values of mean SMA flow were compared with those under anesthesia (30 min), PAM (restrained or unrestrained at 90 and 150 min), and reanesthesia. Sham-anesthetized unrestrained animals provided control values. The same animals (n = 7) underwent the restrained, unrestrained, and control experiments at least 5 days apart. Ketamine anesthesia did not significantly alter mean SMA flow (89 +/- 9% of baseline) compared with sham-anesthetized controls (99 +/- 9%). Mean SMA flow in both PAM, restrained and unrestrained, had a significant (P less than 0.05) decrease at 90 min (78 +/- 8 and 83 +/- 12%) and at 150 min (68 +/- 14 and 78 +/- 14%) when compared with baseline and control. Reanesthesia returned SMA flows to baseline values (91 +/- 16%). The variability of mean SMA flow was significantly increased in both PAM. Maximum variability was observed in the restrained model (69 +/- 32%). These results indicate 1) that ketamine anesthesia does not significantly alter SMA flow and 2) that both the restrained and unrestrained PAM exhibit significant alterations of the splanchnic circulation for at least 2 h after complete recovery from anesthesia. Thus, in the absence of critical evaluation, results of splanchnic hemodynamic studies with these models should be questioned.(ABSTRACT TRUNCATED AT 250 WORDS)

Na restriction blunts expansion of plasma volume and ameliorates hyperdynamic circulation in portal hypertension.

Expansion of plasma volume may be necessary for the development of the hyperdynamic circulation in portal hypertension. In experiment 1, sham portal vein-constricted (sham PVL) rats were divided into normal diet (NL diet sham) and low-sodium diet (low-Na sham) groups. Data obtained from the NL diet sham group was used as control data in studying portal hypertensive rats, which were also divided into normal diet (NL diet PVL) and sodium-restricted (low-Na PVL) groups on the day of portal vein constriction. There were no hemodynamic differences at 3 wk between sham PVL rats on the two diets. In contrast, sodium restriction in PVL rats resulted in a significant amelioration of the hyperdynamic circulation. In experiment 2, PVL rats were fed a normal diet for 10 days, followed by allocation to NL diet PVL and low-Na PVL groups. The hemodynamic effects of sodium restriction in these animals (studied at 22 and 28 days after PVL) were similar to those observed in experiment 1. A time course for amelioration of the hyperdynamic circulation in PVL rats by sodium restriction is described. Sodium restriction prevents the expansion of the plasma volume in PVL rats. Interference with plasma volume expansion blunts the development of (and can ameliorate) the hyperdynamic syndrome. Plasma volume expansion seems necessary for the development of the hyperdynamic circulation in portal hypertension.

Bile acids do not mediate the hyperdynamic circulation in portal hypertensive rats.

Portal hypertension is accompanied by hyperdynamic systemic and splanchnic circulation. Serum bile acids (BAs), which are elevated in portal hypertension and have vasodilatory properties, have been proposed as mediators of this hyperdynamic circulation. In this study, portal hypertensive rats [accomplished by partial portal vein ligation (PVL)] were gavaged with cholestyramine (PVL-CH) to decrease circulating BA levels. A control group of rats was gavaged with an inert suspension of Metamucil (PVL-ME). The following hyperdynamic parameters were found to be similar in PVL-CH and PVL-ME: mean arterial pressure (119 +/- 6 vs. 124 +/- 5 mmHg), portal pressure (13.2 +/- 0.6 vs. 14.5 +/- 0.5 mmHg), cardiac index (0.33 +/- 0.04 vs. 0.34 +/- 0.03 ml.min-1.g body wt-1), splanchnic blood flow (1.4 +/- 0.13 vs. 1.6 +/- 0.1 ml.min-1.g body wt-1), portosystemic shunting (82 +/- 8 vs. 92 +/- 3%), peripheral arteriolar resistances (344 +/- 74 vs. 387 +/- 29 mmHg.min.ml-1.g body wt), and splanchnic arteriolar resistances (75 +/- 14 vs. 72 +/- 6 mmHg.min.ml-1.g splanchnic wt; 1,471 +/- 150 vs. 1,325 +/- 120 mmHg.min.ml-1.g body wt). BA in PVL-ME (84 +/- 9 microM/l) were similar to those previously observed in untreated PVL and significantly greater than those measured in PVL-CH (25 +/- 4 microM/l; P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)