Intravascular volume loading reversibly decreases airway cross-sectional area

High-resolution computed tomography was used to directly determine the short-term effects of intravascular volume expansion on airway caliber. The change in airway cross-sectional area caused by intravascular volume expansion (30 ml/kg, Ringer's lactate) was studied in six anesthetized mini-pigs within 5 min. Twenty-five of 27 large airways (diameter, 2.01 to 5.0 mm) demonstrated decreased internal cross-sectional area (10.56 +/- 1.26 vs 8.66 +/- 1.03 mm2, p < 0.001). Twenty of 24 small airways (diameter, 0.75 to 2.0 mm) showed decreased internal cross-sectional area (1.82 +/- 0.16 vs 1.44 +/- 0.16 mm2, p < 0.001). These changes were rapidly (< 6 min) reversed by intravascular volume reduction. The external airway cross-sectional area did not change. These data suggest rapid, reversible bronchial mucosal vascular engorgement as a cause of increased airway resistance in heart failure.     

Does airway pressure release ventilation alter lung function after acute lung injury?

BACKGROUND: During airway pressure release ventilation (APRV), tidal ventilation occurs between the increased lung volume established by the application of continuous positive airway pressure (CPAP) and the relaxation volume of the respiratory system. Concern has been expressed that release of CPAP may cause unstable alveoli to collapse and not reinflate when airway pressure is restored. OBJECTIVE: To compare pulmonary mechanics and oxygenation in animals with acute lung injury during CPAP with and without APRV. DESIGN: Experimental, subject-controlled, randomized crossover investigation. SETTING: Anesthesiology research laboratory, University of South Florida College of Medicine Health Sciences Center. SUBJECTS: Ten pigs of either sex. INTERVENTIONS: Acute lung injury was induced with an intravenous infusion of oleic acid (72 micrograms/kg) followed by randomly alternated 60-min trials of CPAP with and without APRV. Continuous positive airway pressure was titrated to produce an arterial oxyhemoglobin saturation of at least 95% (FIO2 = 0.21). Airway pressure release ventilation was arbitrarily cycled to atmospheric pressure 10 times per minute with a release time titrated to coincide with attainment of respiratory system relaxation volume. MEASUREMENTS: Cardiac output, arterial and mixed venous pH, blood gas tensions, hemoglobin concentration and oxyhemoglobin saturation, central venous pressure, pulmonary and systemic artery pressures, pulmonary artery occlusion pressure, airway gas flow, airway pressure, and pleural pressure were measured. Tidal volume (VT), dynamic lung compliance, intrapulmonary venous admixture, pulmonary vascular resistance, systemic vascular resistance, oxygen delivery, oxygen consumption, and oxygen extraction ratio were calculated. MAIN RESULTS: Central venous infusion of oleic acid reduced PaO2 from 94 +/- 4 mm Hg to 52 +/- 9 mm Hg (mean +/- 1 SD) (p < 0.001) and dynamic lung compliance from 40 +/- 6 mL/cm H2O to 20 +/- 6 mL/cm H2O (p = 0.002) and increased venous admixture from 13 +/- 3% to 32 +/- 7% (p < 0.001) in ten swine weighing 33.3 +/- 4.1 kg while they were spontaneously breathing room air. After induction of lung injury, the swine received CPAP (14.7 +/- 3.3 cm H2O) with or without APRV at 10 breaths per minute with a release time of 1.1 +/- 0.2 s. Although mean transpulmonary pressure was significantly greater during CPAP (11.7 +/- 3.3 cm H2O) vs APRV (9.4 +/- 3.8 cm H2O) (p < 0.001), there were no differences in hemodynamic variables. PaCO2 was decreased and pHa was increased during APRV vs CPAP (p = 0.003 and p = 0.005). PaO2 declined from 83 +/- 4 mm Hg to 79 +/- 4 mm Hg (p = 0.004) during APRV, but arterial oxyhemoglobin saturation (96.6 +/- 1.4% vs 96.9 +/- 1.3%) did not. Intrapulmonary venous admixture (9 +/- 3% vs 11 +/- 5%) and oxygen delivery (469 +/- 67 mL/min vs 479 +/- 66 mL/min) were not altered. After treatment periods and removal of CPAP for 60 min, PaO2 and intrapulmonary venous admixture returned to baseline values. DISCUSSION: Intrapulmonary venous admixture, arterial oxyhemoglobin saturation, and oxygen delivery were maintained by APRV at levels induced by CPAP despite the presence of unstable alveoli. Decrease in PaO2 was caused by increase in pHa and decrease in PaCO2, not by deterioration of pulmonary function. We conclude that periodic decrease of airway pressure created by APRV does not cause significant deterioration in oxygenation or lung mechanics.     

Cerebral hemodynamic changes in sleep apnea syndrome and effect of continuous positive airway pressure treatment

BACKGROUND AND OBJECTIVE: A clear association among snoring, sleep apnea, and increased risk of stroke has been shown by previous studies. However, the possible role played by sleep apnea in the pathogenesis of cerebrovascular disease is subject to debate. To evaluate the influence of hemodynamic changes caused by obstructive sleep apnea syndrome (OSAS), we investigated cerebrovascular reactivity to hypercapnia in patients with OSAS. METHODS: The study was performed at baseline and after 1 night and 1 month of nasal continuous positive airway pressure (n-CPAP) therapy, with patients in the waking state (8:00 to 8:30 AM and 5:30 to 6:00 PM) with transcranial Doppler ultrasonography. Cerebrovascular reactivity was calculated with the breath-holding index (BHI). RESULTS: In the baseline condition, compared with normal subjects, patients with OSAS showed significantly lower BHI values in both the morning (0.57 versus 1.40, p < 0.0001) and the afternoon (1.0 versus 1.51, p < 0.0001). Cerebrovascular reactivity was significantly higher in the afternoon than it was in the morning in both patients (p < 0.0001) and controls (p < 0.05). In patients, the BHI returned to normal values, comparable with those of control subjects, after both 1 night and 1 month of n-CPAP therapy. CONCLUSIONS: These findings suggest an association between OSAS and diminished cerebral vasodilator reserve. This condition may be related to the increased susceptibility to cerebral ischemia in patients with OSAS, particularly evident in the early morning.     

Pulmonary hemodynamics in the obstructive sleep apnea syndrome. Results in 220 consecutive patients

We have investigated pulmonary hemodynamics in a large series of consecutive, unselected patients with obstructive sleep apnea syndrome (OSAS). The aims of this study were to evaluate the frequency of pulmonary artery hypertension (PH) in OSAS and to analyze, as far as possible, its mechanisms. Two hundred twenty patients were included on the basis of a polysomnographic diagnosis of OSAS (apnea+hypopnea index > 20). PH, defined by a resting mean pulmonary artery mean pressure (PAP) of at least 20 mm Hg, was observed in 37 of 220 patients (17%). Patients with PH differed from the others with regard to pulmonary volumes (vital capacity [VC], FEV1) and the FEV1/VC ratio that were significantly lower (p < 0.001); PaO2 (64.4 +/- 9.3 vs 74.7 +/- 10.1 mm Hg; p < 0.001); PaCO2 (43.8 +/- 5.4 vs 37.6 +/- 3.9 mm Hg; p < 0.001), apnea+hypopnea index (100 +/- 33 vs 74 +/- 32; p < 0.001), and mean nocturnal arterial oxygen saturation (SaO2) (88 +/- 6% vs 94 +/- 2%; p < 0.001). Patients with PH were also more overweight (p < 0.001). Multiple regression analysis showed that 50% of the variance of PAP could be predicted by an equation including PaCO2 (accounting for 32% of the variance), FEV1 (12%), airway resistance (4%), and mean nocturnal SaO2 (2%). In conclusion, PH is observed, in agreement with previous studies, in less than 20% of OSAS patients. PH is strongly linked to the presence of an obstructive (rather than restrictive) ventilatory pattern, hypoxemia, and hypercapnia, and is generally accounted for by an associated obstructive airways disease. In this regard, the severity of OSAS plays only a minor role.     

The effect of zardaverine, an inhibitor of phosphodiesterase isoenzymes III and IV, on endotoxin-induced airway changes in rats

Zardaverine is a novel phosphodiesterase III/IV inhibitor, developed as a potential therapeutic agent for asthma. In this study we evaluated the effect of zardaverine in an in vivo animal model of airway inflammation and hyperresponsiveness. Endotoxin exposure in rats causes a transient increase in airway responsiveness and a neutrophilic inflammation of the bronchi, which are both at least partly mediated through the secondary release of tumour necrosis factor alpha (TNF alpha). Groups of 10 animals each were pretreated with placebo or zardaverine (1, 10, 30 mumol/kg) i.p., 30 min prior to exposure to aerosolized endotoxin (LPS) or saline. Ninety minutes later, airway responsiveness to 5-HT was assessed and bronchoalveolar lavage (BAL) performed. Zardaverine did not influence baseline lung resistance (RL), but inhibited dose dependently the 5-HT induced increase in RL in control animals. In placebo pretreated animals LPS exposure caused a significant decrease in PC50RL5-HT (provocative concentration of 5-HT causing a 50% increase in RL), compared to the saline exposed control group (1.1 +/- 0.1 vs 2.7 +/- 0.4 micrograms/kg) (P < 0.01). This decrease in PC50RL5-HT was significantly inhibited by zardaverine 30 mumol/kg (5.4 +/- 1.8 vs 1.1 +/- 0.1 micrograms/kg) (P < 0.05). Compared to placebo pre-treated, LPS exposed animals, zardaverine 30 mumol/kg also significantly inhibited to LPS induced neutrophil increase (193.0 +/- 50.0 vs 915.6 +/- 181.3 x 10(3)) (P < 0.01), increase in elastase activity (23 +/- 11 vs 54 +/- 9 nmol substrate/h/ml) (P < 0.05) and TNF alpha release in BAL fluid (93.1 +/- 19.5 vs 229.5 +/- 24.8 U/ml BAL fluid) (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Laryngeal mask airway vs face mask and Guedel airway during pediatric myringotomy

OBJECTIVE: To compare perioperative conditions when a face mask and Guedel oral airway (FM-OA) or a laryngeal mask airway (LMA) are used to maintain airway patency during bilateral myringotomy with insertion of tympanostomy tubes (BMT). DESIGN: Randomized controlled trial in children's hospital tertiary-care operating rooms. PARTICIPANTS: Fifty healthy children undergoing BMT procedures during halothane--nitrous oxide (N2O) anesthesia. INTERVENTIONS: During BMT we managed the airway by inserting a Guedel oral airway or an LMA. MAIN OUTCOME MEASURES: We recorded the time taken to insert the airway device along with oxygen saturation during the operation and time from the end of surgery to eye opening, response to commands, and home readiness. In addition the surgeon assessed perioperative conditions on a 10-point scale (1, poor, through 10, excellent). RESULTS: Although insertion of the LMA took longer than the Guedel oral airway (mean +/- SD, 9 +/- 2 seconds vs 6 +/- 2 seconds; P < .05), no differences were noted in the actual operating, anesthesia, or recovery times. However, the frequency of hypoxemic episodes was decreased (8% vs 36%, P < .05) and the lowest recorded oxygen saturations were higher (mean +/- SD, 95% +/- 7% vs 88% +/- 12%; P < .05) in the LMA group than in the FM-OA group. Surgeons rated perioperative conditions better when the LMA was used (median score, 9 vs 8; P < .05). CONCLUSION: The LMA is an excellent alternative to the FM-OA technique for airway maintenance in children undergoing BMT procedures during halothane--N2O anesthesia.     

Comparison of gas exchange and hemodynamic variables during 2 types of exercise tests. Cycle-ergometry and the ergometric table

The development of stress echocardiography on an ergometric table has increased the number of stress tests in the decubitus position, whereas most of the information currently available concerns stress tests in the sitting position or on the treadmill. In order to study the influence of this position of stress testing, the authors compared the results obtained in a series of 15 patients without cardiac disease (Group I) and another series of 15 coronary patients (Group II) undergoing the two types of stress testing, in the vertical position on a bicycle ergometer and in the lateral decubitus position on the ergometric table. Effort tolerance on the bicycle ergometer was significantly greater in terms of work load (202 +/- 35 vs 180 +/- 36 watts (p < 0.001) in the controls, and 120 +/- 32 vs 106 +/- 22 watts (p < 0.05) in the coronary group), of duration of effort (19 +/- 3 vs 16 +/- 3 minutes (p < 0.001) in the controls and 10 +/- 3 vs 8 +/- 2 minutes (p < 0.05) in the coronary patients), of heart rate (190 +/- 10 vs 172 +/- 21 beats/min (p < 0.005) in controls and 118 +/- 19 vs 111 +/- 14 beats/min (p < 0.05) in the coronary patients). On the other hand, blood pressure and O2 saturation tended to be greater during exercise in the decubitus position: SBP 200 +/- 23 vs 196 +/- 27 mmHg (NS) in the controls and 158 +/- 21 vs 166 +/- 23 mmHg (NS) in the coronary patients; DBP 97 +/- 10 vs 102 +/- 27 mmHg (NS) in the controls and 85 +/- 6 vs 90 +/- 10 mmHg (NS) in the coronary patients; O2 sat 96.8 +/- 1 vs 97.6 +/- 0.8% (p < 0.05) in the coronary patients. The anaerobic threshold and peak VO2 were much higher during exercise in the sitting position: oxygen consumption at the threshold 14.8 +/- 3.8 vs 12.6 +/- 2.3 ml.kg-1.min-1 (p < 0.01), peak VO2 22.2 +/- 5.9 vs 18.8 +/- 4.7 ml.kg-1.min-1 (p < 0.01) in the coronary patients. The results of this study show that the cardiovascular stimulation obtained in the decubitus position is not identical to that obtained by traditional exercise stress testing, particularly in coronary patients.     

Physiological dead space/tidal volume ratio during face mask, laryngeal mask, and cuffed oropharyngeal airway spontaneous ventilation

OBJECTIVE: To compare the physiological dead space/tidal volume ratio and arterial to end-tidal carbon dioxide tension (ETCO2) difference during spontaneous ventilation through a face mask, a laryngeal mask (LMA), or a cuffed oropharyngeal airway. DESIGN: Prospective, randomized, cross-over study. SETTING: Inpatient anesthesia at a university department of orthopedic surgery. PATIENTS: 20 ASA physical status I and II patients, without respiratory disease, who underwent ankle and foot surgery. INTERVENTIONS: After a peripheral nerve block was performed, propofol anesthesia was induced and then maintained with a continuous intravenous (i.v.) infusion (4 to 6 mg/kg/h). A face mask, a cuffed oropharyngeal airway, or an LMA were placed in each patient in a random sequence. After 15 minutes of spontaneous breathing through each of the airways, ventilatory variables, as well as arterial, end-tidal, and mixed expired CO2 partial pressure, were measured, and physiological dead space/tidal volume ratio was calculated. MEASUREMENTS AND MAIN RESULTS: Expired minute volume and respiratory rate (RR) were lower with LMA (5.6 +/- 1.2 L/min and 18 +/- 3 breaths/min) and the cuffed oropharyngeal airway (5.7 +/- 1 L/min and 18 +/- 3 breaths/min) than the face mask (7.1 +/- 0.9 L/min and 21 +/- 3 breaths/min) (p = 0.0002 and p = 0.013, respectively). Physiological dead space/tidal volume ratio and arterial to end tidal CO2 tension difference were similar with the cuffed oropharyngeal airway (3 +/- 0.4 mmHg and 4.4 +/- 1.4 mmHg) and LMA (3 +/- 0.6 mmHg and 3.7 +/- 1 mmHg) and lower than with the face mask (4 +/- 0.5 mmHg and 6.7 +/- 2 mmHg) (p = 0.0001 and p = 0.001, respectively). CONCLUSION: Because of the increased dead space/tidal volume ratio, breathing through a face mask required higher RR and expired minute volume than either the cuffed oropharyngeal airway or LMA, which, in contrast, showed similar effects on the quality of ventilation in spontaneously breathing anesthetized patients.     

The effect of salmeterol on nocturnal symptoms, airway function, and inflammation in asthma

STUDY OBJECTIVE: To determine the efficacy of salmeterol alone in a group of patients with moderate asthma with nocturnal worsening of symptoms. DESIGN: Double-blind, randomized, placebo-controlled crossover study. SETTING: Tertiary care hospital specializing in respiratory diseases. PARTICIPANTS: Ten patients with nocturnal asthma. INTERVENTIONS: Subjects were randomized to salmeterol, 100 micrograms twice daily, or placebo for 6 weeks with a 1-week washout between treatment periods. Symptoms, nocturnal awakenings, and beta 2-agonist use were recorded daily. Spirometry was performed at weeks 1 and 6 of each period at bedtime and at 4 AM, and methacholine challenge was performed at 4 AM followed by bronchoscopy with BAL. BAL fluid analysis included cell count and differential count, eosinophil cationic protein, Charcot-Leyden crystal protein, leukotriene B4, and thromboxane B2. RESULTS: The percentage of nights with awakenings decreased significantly with salmeterol (69.8 +/- 8.7% vs 30.6 +/- 10.8% for placebo and salmeterol, respectively; p = 0.02). The percentage of 24-h days with supplemental inhaled beta 2-agonist use significantly decreased with salmeterol (85.9 +/- 9.4% vs 70.4 +/- 10.1% for placebo and salmeterol, respectively; p = 0.04). There were no significant differences in bronchial reactivity, 4 AM FEV1, overnight percentage change in FEV1, or indexes of airway inflammation. CONCLUSIONS: Salmeterol alone improves the number of nocturnal awakenings and supplemental 24-h beta 2-agonist use in nocturnal asthma without significantly altering lung function and airway inflammation.     

Inhaled gentamicin reduces airway neutrophil activity and mucus secretion in bronchiectasis

To investigate whether aerosolized gentamicin (GM) prevents myeloperoxidase (MPO)-mediated airway injury and mucus hypersecretion, a short course of aerosol therapy (3 d) with GM 40 mg or 0.45% saline (saline) twice per day was conducted. Twenty-eight patients with bronchiectasis and mucus hypersecretion after adequate chest care and hydration were enrolled in a randomized, double-blind fashion. MPO levels in sputum collected on arising were determined by fluorometric assay at 655 nm before and after treatment. The sputum MPO level significantly decreased in patients receiving aerosolized GM, from 0.22 +/- 0.04 to 0.14 +/- 0.04 U/g (n = 15), but not in patients with saline inhalation (0.23 +/- 0.03 to 0.17 +/- 0.02 U/g; n = 11). The daily sputum amount significantly decreased from 94.6 +/- 21.6 to 58.1 +/- 17.8 ml (n = 13, p < 0.01) in the GM group, whereas it increased from 78.6 +/- 25.4 ml to 120.5 +/- 33.9 ml (n = 11, p < 0.05) in the saline group. The change in the amount of daily sputum was related to that in the sputum MPO level in the GM group (r = 0.61; p < 0.01). Inhalation of GM, but not saline, significantly (p < 0.05) increased the value of peak expiratory flow (PEF) from 186.4 +/- 25.1 to 216.4 +/- 26.4 L/min and decreased the variability of PEF from 24.6 +/- 5.1 to 6.1 +/- 2.3 %. The nocturnal desaturation and the 6-min walking distances were also significantly improved in the GM group (11.2 +/- 3.8 to 0.6 +/- 0.5 min/h; 324.9 +/- 43.1 to 408.1 +/- 25.9 m; p < 0.05; respectively), but not in the saline group. Subjective improvements in the Borg scale and self-sputum assessment were found in the GM group only. In conclusion, aerosolized GM is effective in improving airway hypersecretion and inflammation in patients with bronchiectasis.     

Relation of endothelins to volume regulating neurohumoral systems in patients with cirrhosis of the liver

The aim of the present study was to investigate the relationship between ET plasma concentrations and other hormonal systems in acute volume regulation of patients with cirrhosis. Ten healthy controls and 10 cirrhotic patients, five without and five with ascites were studied after 1 h in a sitting posture and subsequently subjected to 1 h head-out water immersion. Blood was collected for determinations of ET-1, ET-3, ANF, aldosterone, renin activity and noradrenaline. In addition, in 10 patients with compensated cirrhosis the effect of loop diuretics on ET-3, aldosterone and renin was studied. ETs in cirrhosis were significantly (P < 0.01) higher than in controls both before (ET-1, 19.6 +/- 1.3 pgmL-1 vs. 11.8 +/- 0.4 pgmL-1; ET-3, 18.5 +/- 1.4 pgmL-1 vs. 9.5 +/- 0.5 pgmL-1) and after water immersion (ET-1, 18.6 +/- 1.2 pgmL-1 vs. 12.4 +/- 0.3 pgmL-1; ET-3, 18.7 +/- 1.7 pgmL-1 vs. 10.0 +/- 0.5 pgmL-1). In cirrhotic patients, basal and immersion concentrations of ET-1 were significantly correlated to noradrenaline plasma concentrations (r = 0.79, P < 0.05). ET-3 plasma concentrations in cirrhosis were correlated to renin activity (r = 0.65, P < 0.05). Furthermore, ET-3 in cirrhosis was inversely correlated to systolic and mean arterial blood pressure (r = -0.55, P < 0.01 and r = -0.50, P < 0.05; respectively). To investigate the effect of hypovolaemia in compensated cirrhosis, 10 patients without ascites were studied before and after treatment with loop diuretics. In compensated cirrhosis ET-3 was significantly increased 6h after oral diuretic treatment (17.9 +/- 1.0 pgmL-1 vs. 15.5 +/- 0.4 pgmL-1, P < 0.001). The presented data demonstrate relations of endothelins, particularly of ET-3 to neurohumoral systems in patients with cirrhosis of the liver.     

Reversibility of changes in left and right ventricular geometry and hemodynamics in pulmonary hypertension. Echocardiographic characteristics before and after pulmonary thromboendarterectomy

Pulmonary thromboendarterectomy (PTE) leads to an acute decrease of right ventricular (RV) afterload in patients with chronic thromboembolic pulmonary hypertension. We investigated the changes in right and left ventricular (LV) geometry and hemodynamics by means of transthoracic echocardiography. The prospective study was performed in 14 patients (8 female, 6 male; age 55 +/- 20 years) before and 18 +/- 12 days after PTE. Total pulmonary vascular resistance and systolic pulmonary artery pressure were significantly decreased (PVR: preoperative 986 +/- 318, postoperative 323 +/- 280 dyn x s/cm5, p < 0.05; PAP preoperative 71 +/- 40, postoperative 41 +/- 40 mm Hg + right atrial pressure, p < 0.05). End diastolic and end systolic RV area decreased from 33 +/- 12 to 23 +/- 8 cm2, respectively, from 26 +/- 10 to 16 +/- 6 cm2, p < 0.05. There was an increase in systolic RV fractional area change from 20 +/- 12 to 30 +/- 16%, p < 0.05. RV systolic pressure rise remained unchanged (516 +/- 166 vs. 556 +/- 128 mm Hg/sec). LV ejection fraction remained within normal ranges (64 +/- 16 vs. 62 +/- 12%). Echocardiographically determined cardiac index increased from 2.8 +/- 0.74 to 4.1 +/- 1.74 l/min/m2. A decrease in LV excentricity indices (end diastolic: 1.9 +/- 1 vs. 1.1 +/- 0.3, end systolic: 1.7 +/- 0.6 vs. 1.1 +/- 0.4, p < 0.05) proved a normalization of preoperatively altered septum motion. LV diastolic filling returned to normal limits: (E/A ratio: 0.62 +/- 0.34 vs. 1.3 +/- 0.8; p < 0.05); Peak E velocity: 0.51 +/- 0.34 vs. 0.88 +/- 0.28 m/sec, p < 0.05; Peak A velocity: 0.81 +/- 0.36 vs. 0.72 +/- 0.42 m/sec, ns; E deceleration velocity: 299 +/- 328 vs. 582 +/- 294 cm/sec2, p < 0.05; Isovolumic relaxation time: 134 +/- 40 vs. 83 +/- 38 m/sec, p < 0.05). We could show a marked decrease in RV afterload shortly after PTE with a profound recovery of right ventricular systolic function--even in case of severe pulmonary hypertension. A decrease in paradoxic motion of the interventricular septum and normalization of LV diastolic filling pattern resulted in a significant increase of cardiac index.     

Inhibitory effect of low molecular weight heparin on the bronchoconstriction in ovalbumin-sensitized guinea pigs after antigen exposure

To elucidate the effect of low molecular weight heparin (LMWH) on the bronchoconstriction, we examined the serial changes of the resistance of respiratory system (Rrs) in ovalbumin (OA)-sensitized guinea pigs after antigen exposure. After sensitization of guinea pigs with repeated OA inhalation, Rrs was measured at immediate asthmatic response (IAR) and late asthmatic response (LAR) with or without LMWH inhalation. Alteration in the number of inflammatory cells of the lung by LMWH inhalation was examined in the broncholaveolar lavage fluid (BALF) and in the histological sections of airway walls. Peak Rrs at 1 min up to 9 min, except 8 min, after antigen exposure significantly decreased by the pretreatment with LMWH inhalation as compared with saline inhalation. Peak Rrs at LAR (after 4 hours up to 24 hours, except 6 hours) also showed a significant decrease in the pretreatment with LMWH inhalation. Pretreatment of LMWH exhibited a decrease of eosinophil percentage in BALF (5.5 +/- 1.2% from 8.2 +/- 0.4% in saline inhalation) and a decrease of infiltrated eosinophil count in airway walls (71.0 +/- 7.3 from 155 +/- 15.8 in saline inhalation). These data show LMWH might play an important role as an inhibitory factor to bronchial asthma.     

Mutations in fibroblast growth-factor receptor 3 in sporadic cases of achondroplasia occur exclusively on the paternally derived chromosome

OBJECTIVES: The aim of this study was to determine whether the combination of lipid-lowering therapy and vitamin E supplementation improves peripheral endothelial function and whether it is more effective than lipid-lowering therapy alone. BACKGROUND: Endothelium-dependent vasodilation is impaired in coronary and peripheral arteries of patients with hypercholesterolemia. Coronary endothelial function has been shown to improve under lipid-lowering and antioxidant therapy, but the effect of additive vitamin E supplementation in the brachial artery is unknown. METHODS: Seven patients with hypercholesterolemia (mean+/-SD; age 51+/-10 yr) were studied. Endothelium-dependent, flow-mediated dilation (FMD) and endothelium-independent nitroglycerin-induced dilation (NMD) were assessed in the brachial artery using high resolution ultrasound 1) at baseline (BL I), 2) after 8 weeks of simvastatin (20 mg) and vitamin E (300 IU) therapy (Comb I), 3) after withdrawal of vitamin E for 4 weeks (Statin), 4) after therapy as in #2 for 4 weeks (Comb II) and 5) after withdrawal of both drugs for 4 weeks (BL II). RESULTS: Combined simvastatin and vitamin E therapy reduced total cholesterol (Comb I vs. BL I: 276+/-22 vs. 190+/-14 mg/dl, p < 0.0001) and low-density lipoprotein (LDL)-C (197+/-22 vs. 106+/-22 mg/dl, p < 0.00001), augmented alpha tocopherol levels normalized to LDL (12.2+/-4.1 vs. 4.9+/-0.9 microg alpha-T/100 mg% LDL-C, p < 0.01) and resulted in significant improvements in FMD (16.4+/-4.7 vs. 4.9+/-2.5%, p < 0.001) as well as NMD (17.9+/-4.3 vs. 11.2+/-2.8%, p < 0.01). The ratio of FMD to NMD (0.92+/-0.17 vs. 0.46+/-0.24%, p < 0.05) also increased under combination therapy, indicating a greater improvement of FMD than that of NMD. After withdrawal of vitamin E, both FMD (Comb I vs. Statin: 16.4+/-4.7 vs. 7.9+/-4.7%, p < 0.01) and NMD (17.9+/-4.3 vs. 10.9+/-4.5%, p < 0.05) decreased significantly such that simvastatin alone only tended to improve FMD and did not change NMD. Results under combination therapy (Comb II vs. BL II) were reproducible. CONCLUSIONS: Combined vitamin E and simvastatin therapy leads to an improvement of FMD and NMD in the brachial artery of patients with hypercholesterolemia. The improvement of FMD is more pronounced after combination therapy than after lipid-lowering therapy alone, similar to previous findings in the coronary circulation.     

Differences in airway closure between normal and asthmatic subjects measured with single-photon emission computed tomography and technegas

The absence of a maximal dose-response plateau as well as gas trapping and increases in closing capacity (CC) suggest that increased airway closure is an important mechanical abnormality of asthmatic airways. We compared the extent and distribution of airway closure in 13 normal and in 23 asthmatic subjects. Airway closure (LVclosed) was measured with single-photon emission computed tomography (SPECT) and an inhaled Technegas bolus as the percentage of lung volume without Technegas (LVtrans), and with CC, using nitrogen washout. LVclosed was compared in the apical, middle and lower zones, each being of equal vertical height. Values of mean LVclosed +/- 95% confidence interval (CI) were similar in normal (30 +/- 6.0% LVtrans) and asthmatic subjects (30 +/- 7.8% LVtrans). In normal subjects, LVclosed correlated with both age (r = 0.89, p < 0. 01) and CC (r = 0.86, p < 0.01), was more extensive in the lower zone (58 +/- 18.8% LVtrans, p < 0.01) than in the middle and upper zones (17 +/- 8.7% and 26 +/- 8.2 LVtrans, respectively), and increased with age in both the middle and lower zones (r = 0.94 and r = 0.90, respectively, p < 0.01). In asthmatic subjects, LVclosed did not correlate with age; was greatest in the lower zone, intermediate in the middle zone, and lowest in the apical zone (59 +/- 13.2%, 22 +/- 5.8%, and 12 +/- 4.4% LVtrans, respectively, p < 0. 01); and correlated weakly with age in the middle zone only (r = 0. 46, p < 0.05). We conclude that there is a predictable pattern of airway closure in normal subjects and that it is primarily influenced by pulmonary elastic recoil. This pattern is lost in asthmatic subjects. This may be explained by an increased range of closing pressures and a patchy distribution of airway closure, probably secondary to allergic inflammation.     

Dexfentluramine in the treatment of juvenile obesity

BACKGROUND: The aim of this study was to investigate the potential of dexfenfluramine (dF) for reducing cardiovascular risk factors and improving compliance towards diet in a group of young patients hospitalized for essential obesity of high degree (BMI > or = 35). METHODS: 103 adolescents (mean age 15.4 +/- 0.2) participated in a nine-week randomized double-blind study of dF (15 mg bid) versus placebo. All patients received a VLCD (2,512 kJ/day = 600 kcal/day) for two months. In basal conditions, and after 30 and 60 days of treatment, anthropometric variables (height, weight, BMI, and W/H) and cardiovascular risk factors (blood glucose concentration, total cholesterol, HDL-cholesterol, triglycerides, systolic and diastolic blood pressure) were monitored. Modifications in hunger and satiety were also assessed. RESULTS: During the treatment period, both the dF group and the placebo group presented a similar pattern of weight loss (BMI = dF: 36.7 +/- 0.5 vs 32.5 +/- 0.4 vs 30.1 +/- 0.4; placebo: 37.0 +/- 0.6 vs 33.1 +/- 0.5 vs 30.8 +/- 0.5). No important side-effects were recorded in either group. Blood pressure and metabolic markers decreased significantly in both groups. Earlier reductions in total cholesterol and diastolic blood pressure in dF-treated subjects were the only significant differences observed as compared to the patients receiving placebo (day 30 = total cholesterol: 120 +/- 2 (dF) vs 132 +/- 3 (placebo) mg/dI; p < 0.005; diastolic blood pressure: 73 +/- 1 (dF) vs 77 +/- 1 (placebo) mmHg; p < 0.01). However, after 60 days, these values were similar in the two groups. As far as non-parametric data are concerned, dF determined a reduction in hunger and an increase in satiety in a significantly higher number of subjects than did the placebo, not only after 30 days of treatment (92.8% vs 55.3% and 92.8% vs 45.5%, respectively; p < 0.0001), but also after two months of treatment (97.8% vs 67.4% and 97.8% vs 45.8%, respectively; p < 0.0001). CONCLUSIONS: These findings demonstrate that dF represents a useful support in the treatment of juvenile obesity and might ensure a better individual compliance towards restrictive diets, particularly in the initial "critical" stages, in the absence of important side-effects.     

Overnight normalization of glucose concentrations improves hepatic but not extrahepatic insulin action in subjects with type 2 diabetes mellitus

Subjects with poorly controlled type 2 diabetes are both hyperglycemic and insulin resistant. To determine whether short term restoration of normoglycemia improves insulin action, hyperinsulinemic (approximately 300 pmol/L) euglycemic clamps were performed in diabetic subjects after either overnight infusion of saline or overnight infusion of insulin in amounts sufficient to maintain euglycemia throughout the night. Fasting glucose concentrations (5.2 +/- 0.2 vs. 11.9 +/- 1.4 mmol/L; P < 0.01) and rates of endogenous glucose production (13.0 +/- 1.1 vs. 18.6 +/- 1.6 mumol/kg.min; P < 0.05) were both lower after overnight insulin than overnight saline. Insulin-induced stimulation of glucose uptake (to 34.9 +/- 6.8 vs. 28.8 +/- 3.4 mumol/kg.min; P = 0.2) and inhibition of free fatty acids (to 0.13 +/- 0.03 vs. 0.12 +/- 0.04 mmol/L; P = 0.6) did not differ after overnight saline and overnight insulin. In contrast, endogenous glucose production during the final hour of the hyperinsulinemic clamps (i.e. when glucose concentrations were the same) remained higher (P = 0.05) after overnight saline than after overnight insulin (5.5 +/- 1.5 vs. 0.02 +/- 1.4 mumol/kg.min). Thus, acute restoration of euglycemia by means of an overnight insulin infusion improves hepatic (and perhaps renal) but not extrahepatic insulin action.     

Diastolic dysfunction in patients with chronic kidney failure on a hemodialysis program

OBJECTIVE: The aim of this study was to analyse different ultrasound parameters for the assessment of isolated left ventricular diastolic dysfunction (LVDD) in patients with chronic renal failure (CRF) on periodic hemodialysis (HD), comparing pulsed wave Doppler with pulsed tissue Doppler. MATERIALS AND METHODS: Forty-seven patients with CRF on HD (61% were male; mean age was 51.0 +/- 16.5 years, mean HD time--3.7 +/- 3.8 years, 38% had hypertension, 17% had diabetes) were studied by echocardiography (bidimensional, M-Mode, flow pulsed Doppler and tissue Doppler imaging). All patients had symptoms of left heart failure-class II NYHA, were in sinus rhythm and had no symptoms of ischemic heart disease. The presence of abnormal LV regional contractility was the exclusion criteria. According to their mitral inflow profile Doppler characteristics, patients were included in two groups: Group A (E/A > 1; n = 21) and B (E/A < 1; n = 26). We compared: LV dimensions and function, left atrial (LA) dimension. Gaasch index, LV mass index. E and A wave velocities (in flow pulsatile Doppler and tissue Doppler). E/N ratio in tissue Doppler, isovolumetric relaxation time (IVRT) and deceleration time (DT). RESULTS: There were no significant differences in the prevalence of age > or = 65 years male sex, hypertension or diabetes between group A and B patients, and almost all patients were on hemodialytic treatment for more than one year (81% vs 85%: NS). LV hypertrophy was present in almost all group A and B patients (A--95% vs B--85.5%; NS). Group A, compared with group B, had a difference in the Gaasch index (2.45 +/- 0.3 vs 2.08 +/- 0.4; p < 0.05), E wave velocity in flow pulsatile Doppler and tissue Doppler (cm/sec) (110 +/- 27 vs 62 +/- 20; p < 0.001 and 41 +/- 15 vs 28.5 +/- 16; p < 0.05), E/A ratio in tissue Doppler (1.3 +/- 0.4 vs 0.8 +/- 0.3; p < 0.001). IVRT (msec) (80.7 +/- 15.2 vs 113.5 +/- 28.3; p < 0.001) and DT (msec) (189.7 +/- 24 vs 278.2 +/- 17.9; p < 0.001). According to the E'/A' ratio in tissue Doppler, group A patients were divided in another two groups: E'/A' > 1 (13/21--62%) and < 1 (8/21--38%) and a significantly longer IVRT (75.8 +/- 9.3 vs 100.9 +/- 3.2; p < 0.001) and DT (178 +/- 15 vs 240 +/- 20; p < 0.001) and a greater LA dimension (37.6 +/- 6.9 vs 44.6 +/- 6.9; p < 0.05) were found. CONCLUSIONS: Pulsed wave Doppler is the most useful non invasive method for assessment of global diastolic dysfunction. In our study, 17% of the patients had E/A < 1 only in the tissue Doppler study. These patients probably had a pseudonormal mitral pattern.     

Anamnestic and polygraphic parameters in obstructive sleep apnea syndrome patients with reduced nasal respiration during the day in comparison with obstructive sleep apnea patients with normal nasal respiration

Nasal obstruction is a predictive factor for snoring and may contribute to the development of an obstructive sleep apnea syndrome (OSAS). The aim of this study was to further evaluate the impact of nasal obstruction in OSAS. Therefore, we investigated 2 groups of OSAS-patients, matched pairs concerning gender, age, and BMI: OSAS-patients with nasal obstruction (N, n = 28), total nasal airflow < 500 ccm/s (referred to 150 pa pressure of difference or unilateral nasal resistance > 1 pa/ccm/s), and 28 OSAS-patients without nasal obstruction (control-group K, total nasal airflow > 700 ccm/s [referred to 150 pa pressure of difference or unilateral nasal resistance > 1 pa/ccm/s]). We performed anterior rhinomanometry, lung-function testing, cardio-respiratory polygraphy, and patients answered a standardized questionnaire. We found the following significant differences: 1) N complained more often (n = 17) about dyspnea at night than K (n = 7, p < 0.05, Chi2-test). 2) N had a higher apnea index (20.4 +/- 19.0/h) than K (9.6 +/- 10.0/h, p < 0.05, Student's t-test). There were, however, no significant differences concerning lung function, number of nocturnal hypopneas, nocturnal SaO2 and heart rate. Our results underline the importance of nasal ventilation in the pathogenesis of OSAS. At least in moderate cases of OSAS a therapy of nasal obstruction might be of success in order to abolish nCPAP-therapy or might reduce nasal problems during nCPAP-therapy and thus ameliorate patient's therapy compliance.     

Outpatient management program of patients with chronic heart failure

Hospitalization of patients with heart failure is often caused by poor adherence to drug therapy, by suboptimal utilization of ACE inhibitors and beta-blockers, and by the lack of systematic monitoring of patients after discharge. The aim of the study is to verify the impact of an outpatient management program on the hospitalization rate and functional status of patients with chronic heart failure. Over a five-year period, 435 patients entered our outpatient management program, which includes adjustment in medical therapy, patient education and visits timed according to the patient's status. Fifty-six percent of the patients were in New York Heart functional class I-II; 74% were male; mean age was 62 +/- 11 years. Heart failure was due to coronary heart disease in 42%, dilated cardiomyopathy in 35%, hypertensive heart disease in 13%, other etiologies in 10%. The following changes in medical therapy were made compared to the period before referral: ACE inhibitors in 88% of the patients vs 70% (p < 0.05), mean dose of enalapril and captopril respectively 18 +/- 6 mg vs 11 +/- 4 mg (p < 0.05) and 89 +/- 28 mg vs 61 +/- 34 mg (p < 0.05); digoxin in 71 vs 70% (NS); furosemide in 90 vs 87%; beta-blockers in 16 vs 6% (p < 0.05); amiodarone in 24 vs 16% (p < 0.05); oral anticoagulants in 22 vs 12% (p < 0.05); calcium channel blockers in 10 vs 16% (p < 0.05). During the follow-up period (35 +/- 11 months), there were 111 hospital admissions compared to 518 during the year before recruitment (p < 0.05). Seventy-two patients died (65 for cardiac causes) and four patients underwent cardiac transplantation. Functional status improved (301 patients in I-II functional class and 56 in III-IV after referral compared to 225 and 132 before referral, respectively). Our results were obtained through adjustment in pharmacological therapy, intensive patient education and therapeutic continuity made possible by our outpatient heart-failure clinic organization. It is likely that the increase in costs due to therapeutic adjustment and to the increase in the number of visits is counterbalanced by the reduced rate of hospital admissions.