RESUMEN
Studies on the clearance of instilled fluid and protein into the lungs of sheep show that fluid initially clears rapidly from the lungs resulting in an increase in an increase in air space protein concentrations. This is followed by a slower monoexponential clearance of proteins during the next few days. To determine whether the clearance of edema fluid follows the same time course as instilled fluid, alveolar edema was induced in 11 sheep by inflating a balloon in the left atrium for 2 h to increase left atrial pressure 35-40 cm H2O. Protein concentrations in the epithelial lining fluid (ELF) were monitored by performing single-cycle lavages immediately after deflation of the left atrial balloon, and again 3, 21, 48, and 96 h later. During the first 3 h of recovery, 44% of the fluid cleared and ELF protein concentrations rose from 7 +/- 2 to 19 +/- 6 mg/mL in the 7 sheep that recovered well. The ELF protein concentration in these sheep remained elevated for 48 h and then cleared at rates similar to that seen following instillation of proteins. We conclude that insights about mechanisms of clearance of edema fluid obtained from studies of clearance of instilled fluid are valid in cardiogenic edema, but the time course of the clearance differs between the two models.
Asunto(s)
Insuficiencia Cardíaca/complicaciones , Insuficiencia Cardíaca/metabolismo , Proteínas/metabolismo , Alveolos Pulmonares/metabolismo , Edema Pulmonar/metabolismo , Animales , Función del Atrio Izquierdo/fisiología , Líquido del Lavado Bronquioalveolar , Epitelio/metabolismo , Exudados y Transudados/metabolismo , Cinética , Cómputos Matemáticos , Proteínas/farmacocinética , Edema Pulmonar/etiología , OvinosRESUMEN
Salmeterol has been shown to prevent the influx of proteins into the air spaces of lungs of guinea pigs given intravenous histamine. To determine whether the salmeterol acts to stabilize the epithelial or endothelial barrier, we ventilated anesthetized sheep with aerosolized salmeterol before infusing histamine intravenously at a rate of 4 micrograms.kg-1.min-1 for 3 h. Changes in endothelial permeability were assessed by measuring the flow of lymph and proteins from the lungs. The influx of proteins into the air spaces was detected by performing single-cycle lavages to measure the concentration of circulating 125I-albumin in the epithelial lining fluid. Intravenous histamine increased the lymph flow to 13.2 +/- 6.8 ml/h compared with the control value of 5.6 +/- 2.8 ml/h (P < 0.05). Histamine also increased the concentration of 125I-albumin in the epithelial lining fluid from 1.8 +/- 0.9 to 8.5 +/- 2.5% of the plasma concentration (P < 0.01) and the postmortem lung water volume from 3.5 +/- 0.5 to 5.0 +/- 0.8 mg/g dry lung wt (P < 0.05). Pretreatment with 2.5 mg of aerosolized salmeterol prevented the influx of proteins into the air spaces and the increase in the postmortem lung water volume but it also increased the lung lymph flow even further to 20.0 +/- 5.6 ml/h (P < 0.05), increased the lymph-to-plasma protein ratio from 0.77 to 0.91, and tripled the increase in alveolar-arterial oxygen gradient caused by histamine alone. Pretreatment with 2.5 mg of intravenous salmeterol had essentially the same effect as salmeterol administered by aerosol. We conclude that salmeterol decreases lung epithelial permeability but increases lung endothelial permeability due to intravenous histamine in sheep.
Asunto(s)
Albuterol/análogos & derivados , Broncodilatadores/farmacología , Pulmón/efectos de los fármacos , Intercambio Gaseoso Pulmonar/efectos de los fármacos , Albuterol/farmacología , Animales , Endotelio/efectos de los fármacos , Epitelio/efectos de los fármacos , Histamina/farmacología , Xinafoato de Salmeterol , Ovinos , Factores de TiempoRESUMEN
The standard curve of a typical colorimetric assay for total protein is often nonlinear and dependent on the albumin fraction of the protein standard. We developed a simple mathematical transformation to make the standard curve linear and a computational method to correct for differences in albumin concentrations among the samples. This method uses data from total protein assays on two sets of standards (albumin and gamma globulin) and provides accurate measures of total protein over the full range of albumin fractions. Comparison of this two-standard method with the a method that uses only albumin as a standard shows that this method prevents physiologically significant overestimations in total protein concentration and calculated protein osmotic pressure differences in the lungs.
Asunto(s)
Líquidos Corporales/química , Proteínas/análisis , Albúmina Sérica/análisis , Algoritmos , Animales , Modelos Biológicos , Concentración Osmolar , OvinosRESUMEN
An accurate and reproducible measure of solute concentration of lung epithelial lining fluid (ELF) by bronchoalveolar lavage would be valuable in lung research and in patient care. Measurements of the albumin/total protein ratio in a previously proposed rewash lavage procedure showed that albumin enters the lavage fluid. Therefore, the rewash lavage may measure ELF volume accurately, but it overestimates ELF protein concentration (PELF). To avoid problems of solute exchange, we examined five sequential fractions of lavage fluid obtained from sheep after a single 60-ml lavage containing a 99mTcO4- tracer. Assays of albumin, 99mTcO4-, total protein, and endogenous urea concentrations allowed calculation of PELF from each fraction. PELF was 8 +/- 4 mg/ml when calculated from dilution of either endogenous urea or 99mTcO4- in fractions collected after the first 15 to 20 ml. Paired lavages provided a reproducible measure of PELF (SD, 1.2 mg/ml) that was unaffected by any solute exchange that occurred during the 40-s procedure. Accuracy was verified by comparisons of lung lymph and ELF protein concentrations during high pressure lung edema in anesthetized sheep. The single-cycle lavage procedure is an accurate and reproducible procedure for measuring PELF.