Serum mucin antigen (CASA) as a marker of amiodarone-induced pulmonary toxicity.
(25/1644)
Amiodarone is used to treat life-threatening cardiac arrhythmias. Amiodarone-induced pulmonary toxicity (APT) can be difficult to diagnose. APT may result in increased mucus production and mucin expression. Thus, serum mucin-1 was evaluated as a marker for amiodarone-induced pulmonary toxicity. Concentrations of mucin-1 in peripheral blood were determined using cancer-associated serum antigen (CASA) assay in patients taking amiodarone. Eight of ten patients who developed major amiodarone toxicity had high serum CASA levels. Patients with toxicity had a significantly higher mean rank CASA concentration compared with those without major toxicity. CASA shows potential as a marker for amiodarone-induced toxicity, particularly pulmonary toxicity. (+info)
Estimating venous admixture using a physiological simulator.
(26/1644)
Estimation of venous admixture in patients with impaired gas exchange allows monitoring of disease progression, efficacy of interventions and assessment of the optimal inspired oxygen fraction. A pulmonary artery catheter allows accurate measurement, although the associated risks preclude its use solely for estimation of venous admixture. Non-invasive methods require assumed values for physiological variables. Many of the required data (e.g. haemoglobin concentration (Hb), base excess, inspired oxygen fraction, arterial oxygen (PaO2) and carbon dioxide (PaCO2) tensions, temperature) are available routinely in the intensive therapy unit. We have compared a typical iso-shunt-style estimation of venous admixture (assuming Hb, base excess, PaCO2 and temperature), and estimation using the Nottingham physiology simulator (NPS), with measured data. When the arteriovenous oxygen content difference (CaO2-CvO2) was assumed to be 50 ml litre-1, the 95% limits of agreement (LA95%) for venous admixture using the NPS were -3.9 +/- 8.5% and using an iso-shunt-style calculation, -6.4 +/- 10.6%. CaO2-CvO2 was 41.1 ml litre-1 in the patients studied, consistent with previous studies in the critically ill. When CaO2-CvO2 was assumed to be 40 ml litre-1, LA95% values were 0.5 +/- 8.2% and -2.1 +/- 10.1%, respectively. (+info)
Vaporized perfluorocarbon improves oxygenation and pulmonary function in an ovine model of acute respiratory distress syndrome.
(27/1644)
BACKGROUND: Perfluorocarbon liquids are being used experimentally and in clinical trials for the treatment of acute lung injury. Their resemblance to inhaled anesthetic agents suggests the possibility of application by vaporization. The authors' aim was to develop the technical means for perfluorocarbon vaporization and to investigate its effects on gas exchange and lung function in an ovine model of oleic acid-induced lung injury. METHODS: Two vaporizers were calibrated for perfluorohexane and connected sequentially in the inspiratory limb of a conventional anesthetic machine. Twenty sheep were ventilated in a volume controlled mode at an inspired oxygen fraction of 1.0. Lung injury was induced by intravenous injection of 0.1 ml oleic acid per kilogram body weight. Ten sheep were treated with vaporized perfluorohexane for 30 min and followed for 2 h; 10 sheep served as controls. Measurements of blood gases and respiratory and hemodynamic parameters were obtained at regular intervals. RESULTS: Vaporization of perfluorohexane significantly increased arterial oxygen tension 30 min after the end of treatment (P < 0.01). At 2 h after treatment the oxygen tension was 376+/-182 mmHg (mean +/- SD). Peak inspiratory pressures (P < 0.01) and compliance (P < 0.01) were significantly reduced from the end of the treatment interval onward. CONCLUSION: Vaporization is a new application technique for perfluorocarbon that significantly improved oxygenation and pulmonary function in oleic acid-induced lung injury. (+info)
Randomized trial of inhaled fluticasone propionate in chronic stable pulmonary sarcoidosis: a pilot study.
(28/1644)
Pulmonary sarcoidosis is a disease in which the pathological processes are distributed along lymphatic pathways, particularly those around the bronchovascular bundles. Delivery of disease-modulating drugs by the inhaled route is therefore an attractive option. The aim of this study was to determine the efficacy of inhaled fluticasone propionate 2 mg x day(-1) in adults with stable pulmonary sarcoidosis. Forty-four adult patients (22 from each centre) were enrolled from outpatient clinics in two London teaching hospitals in a two centre, double-blind, randomized, placebo-controlled trial. Primary end points were home recordings of peak expiratory flow rate (PEFR), forced expiratory volume in one second (FEV1), and forced vital capacity (FVC). Secondary end points were symptom scores, use of rescue bronchodilator medication, and clinic values for PEFR, FEV1, FVC, forced mid-expiratory flow (FEF25-75%), diffusion capacity of the lung for carbon monoxide (DL,CO), and total lung capacity (TLC). Symptom scores of cough, breathlessness and wheeze were lower in the active treatment group, but this did not reach statistical significance, and a general health perception assessment (Short Form (SF)-36) showed a difference between active and placebo treatment. No significant differences were found between the two groups in any physiological outcome measure. No new adverse reactions were detected. The results of this pilot study do not show an objective benefit of inhaled fluticasone propionate in pulmonary sarcoidosis where the disease is stable and is controlled without the use of inhaled corticosteroids. (+info)
Origin of oscillatory kinetics of respiratory gas exchange in chronic heart failure.
(29/1644)
BACKGROUND: Respiratory gas exchange measurements in patients with chronic heart failure (CHF) at rest and during exercise commonly reveal prominent slow oscillations in ventilation (V(E)), measured oxygen uptake (VO(2)), and carbon dioxide production (VCO(2)), whose origin is not clear. Voluntary simulation of periodic breathing (PB) in normals has been reported to generate a different pattern of oscillations in gas exchange from that seen in spontaneous PB. This necessitates hypothesizing that PB is caused by a primary oscillation in tissue metabolism or in cardiac output. METHODS AND RESULTS: We developed an automated method by which normal controls could be guided to breathe according to a PB pattern. The resultant metabolic oscillations closely matched those seen in spontaneous PB and had several interesting properties. At low workloads (including rest), the oscillations in VO(2) were as prominent as those in V(E) in both spontaneous PB (alpha(VO2)/alpha(VE)=0.92+/-0.04) and voluntary PB (0.93+/-0.07). However, at increased workload, the oscillations in VO(2) because less prominent than those in V(E) in spontaneous PB (intermediate workload 0.63+/-0.05, high workload 0.57+/-0.04; P<0.001) and voluntary PB (intermediate 0.66+/-0.03, high 0.48+/-0.03; P<0.001). There was no difference in the relative size of metabolic oscillations between voluntary and spontaneous PB at matched workloads (P>0.05 at low, intermediate, and high workloads). Furthermore, VO(2) peaked before V(E) in both spontaneous and voluntary PB. This time delay varied from 6.4+/-0.4 s at low ventilation, to 11.3+/-0.9 s at high ventilation (P<0.0001). CONCLUSIONS: The magnitude and phase pattern of oscillations in gas exchange of spontaneous PB can be obtained by adequately matched voluntary PB. Therefore, the gas exchange features of PB are explicable by primary ventilatory oscillation. (+info)
The effects of in vivo pulmonary oxygenation on lung liquid production in near-term fetal sheep.
(30/1644)
Lung liquid (LL) is secreted into the fetal lung lumen, but it must be rapidly absorbed at birth to allow air breathing. In vitro studies have implicated oxygen as a possible factor causing the switch from secretion to absorption of lung liquid at birth. We developed a technique of oxygenating the fetal lung using liquid ventilation with haemoglobin (Hb) solutions in chronically catheterized fetal lambs (129-140 days gestation; term, 147 days). In some experiments 2,3-diphosphoglycerate (DPG) was added to increase oxygen delivery. LL secretion rate (Jv) was measured using an indicator dilution method. Eighteen fetuses were divided into four groups and ventilated with liquid under the following conditions: (i) Hb with oxygen, (ii) Hb without oxygen, (iii) Hb with DPG and oxygen and (iv) Hb and DPG without oxygen. There was a significant rise (2.6 mmHg, P < 0.02) in fetal arterial Po2 in group iii, but in none of the other groups. In the first 3 h of liquid ventilation there was no difference in Jv between the groups. In group i, during hours 4-6 of liquid ventilation, there was a significant rise in secretion rate from 2.25 +/- 0.88 to 3.74 +/- 0.85 ml h-1 kg-1 (P < 0.001). In group iii, when comparing Jv in the first 3 h of liquid ventilation with that in the following 3 h period of liquid ventilation, a strong trend towards reduction in secretion was observed, falling from 3.03 +/- 0.65 to 0.74 +/- 0.92 ml h-1 kg-1 (three of the four experiments showed a significant decrease in Jv in hours 4-6). These experiments indicate that oxygen delivered to the fetus using liquid ventilation with haemoglobin solutions leads to increased LL secretion when oxygen delivery is small, and suggest there is a decrease in secretion with greater oxygen delivery to the lung. (+info)
The effects of caffeine on the kinetics of O2 uptake, CO2 production and expiratory ventilation in humans during the on-transient of moderate and heavy intensity exercise.
(31/1644)
In order to test the hypothesis that glycogen sparing observed early during exercise following caffeine ingestion was a consequence of tighter metabolic control reflected in faster VO2 kinetics, we examined the effect of caffeine ingestion on oxygen uptake (VO2), carbon dioxide production (VCO2) and expiratory ventilation (VE) kinetics at the onset of both moderate (MOD) and heavy (HVY) intensity exercise. Male subjects (n = 10) were assigned to either a MOD (50% VO2,max, n = 5) or HVY (80% VO2,max, n = 5) exercise condition. Constant-load cycle ergometer exercise was performed as a step function from loadless cycling 1 h after ingestion of either dextrose (placebo, PLAC) or caffeine (CAFF; 6 mg (kg body mass)-1). Alveolar gas exchange was measured breath-by-breath. A 2- or 3-component exponential model, fitted through the entire exercise transient, was used to analyse gas exchange and ventilatory data for the determination of total lag time (TLT: the time taken to attain 63% of the total exponential increase). Caffeine had no effect on TLT for VO2 kinetics at either exercise intensity (MOD: 36 +/- 14 s (PLAC) and 41 +/- 10 s (CAFF); HVY: 99 +/- 30 s (PLAC) and 103 +/- 26 (CAFF) (mean +/- S.D.)). TLT for VE was increased with caffeine at both exercise intensities (MOD: 50 +/- 20 s (PLAC) and 59 +/- 21 s (CAFF); HVY: 168 +/- 35 s (PLAC) and 203 +/- 48 s (CAFF)) and for VCO2 during MOD only (MOD: 47 +/- 14 s (PLAC) and 53 +/- 17 s (CAFF); HVY: 65 +/- 13 s (PLAC) and 69 +/- 17 s (CAFF)). Contrary to our hypothesis, the metabolic effects of caffeine did not alter the on-transient VO2 kinetics in moderate or heavy exercise. VCO2 kinetics were slowed by a reduction in CO2 stores reflected in pre-exercise and exercise endtidal CO2 pressure (PET,CO2) and plasma PCO2 which, we propose, contributed to slowed VE kinetics. (+info)
Aerobically generated CO(2) stored during early exercise.
(32/1644)
Previous studies have shown that a metabolic alkalosis develops in the muscle during early exercise. This has been linked to phosphocreatine hydrolysis. Over a similar time frame, the femoral vein blood pH and plasma K(+) and HCO(-)(3) concentrations increase without an increase in PCO(2). Thus CO(2) from aerobic metabolism is converted to HCO(-)(3) rather than being eliminated by the lungs. The purpose of this study was to quantify the increase in early CO(2) stores and the component due to the exercise-induced metabolic alkalosis (E-I Alk). To avoid masking the increase in CO(2) stores by CO(2) released as HCO(-)(3) buffers lactic acid, the transient increase in CO(2) stores was measured only for work rates (WRs) below the lactic acidosis threshold (LAT). The increase in CO(2) stores was evident at the airway starting at approximately 15 s; the increase reached a peak at approximately 60 s and was complete by approximately 3 min of exercise. The increase in CO(2) stores was greater, but the kinetics were unaffected at the higher WR. Three components of the change in aerobically generated CO(2) stores were considered relevant: the carbamate component of the Haldane effect, the increase in CO(2) stores due to increase in tissue PCO(2), and the E-I Alk. The Haldane effect was calculated to be approximately 5%. Physically dissolved CO(2) in the tissues was approximately 30% of the store increase. The remaining E-I Alk CO(2) stores averaged 61 and 68% for 60 and 80% LAT WRs, respectively. The kinetics of O(2) uptake correlated with the time course of the increase in CO(2) stores; the size of the O(2) deficit correlated with the size of the E-I Alk component of the CO(2) stores. We conclude that a major component of the aerobically generated increase in CO(2) stores is the new HCO(-)(3) generated as phosphocreatine is converted to creatine. (+info)