RESUMEN
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Adulto , Femenino , Masculino , Humanos , Ubiquinona/farmacocinética , Ejercicio Físico/fisiología , Coenzimas/farmacocinética , Educación y Entrenamiento FísicoRESUMEN
We studied the effects of fibroblast growth factor (FGF-10) on alveolar epithelial cell (AEC) Na,K-ATPase regulation. Within 30 min FGF-10 increased Na,K-ATPase activity and alpha1 protein abundance by 2.5-fold at the AEC plasma membrane. Pretreatment of AEC with the mitogen-activated protein kinase (MAPK) inhibitor U0126, a Grb2-SOS inhibitor (SH3-b-p peptide), or a Ras inhibitor (farnesyl transferase inhibitor (FTI 277)), as well as N17-AEC that express a Ras dominant negative protein each prevented FGF-10-mediated Na,K-ATPase recruitment to the AEC plasma membrane. Accordingly, we provide first evidence that FGF-10 upregulates (short-term) the Na,K-ATPase activity in AEC via the Grb2-SOS/Ras/MAPK pathway.
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Factores de Crecimiento de Fibroblastos/fisiología , Regulación Enzimológica de la Expresión Génica/efectos de los fármacos , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Metionina/análogos & derivados , ATPasa Intercambiadora de Sodio-Potasio/metabolismo , Butadienos/farmacología , Membrana Celular/metabolismo , Inhibidores Enzimáticos/farmacología , Células Epiteliales/efectos de los fármacos , Células Epiteliales/enzimología , Células Epiteliales/fisiología , Factor 10 de Crecimiento de Fibroblastos , Humanos , Metionina/farmacología , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Modelos Biológicos , Nitrilos/farmacología , Transducción de Señal/efectos de los fármacos , ATPasa Intercambiadora de Sodio-Potasio/genética , Células Tumorales Cultivadas , Proteínas ras/fisiologíaRESUMEN
Short-term mechanical ventilation with high tidal volume (HVT) causes mild to moderate lung injury and impairs active Na+ transport and lung liquid clearance in rats. Dopamine (DA) enhances active Na+ transport in normal rat lungs by increasing Na+-K+-ATPase activity in the alveolar epithelium. We examined whether DA would increase alveolar fluid reabsorption in rats ventilated with HVT for 40 min compared with those ventilated with low tidal volume (LVT) and with nonventilated rats. Similar to previous reports, HVT ventilation decreased alveolar fluid reabsorption by ~50% (P < 0.001). DA increased alveolar fluid reabsorption in nonventilated control rats (by ~60%), LVT ventilated rats (by approximately 55%), and HVT ventilated rats (by ~200%). In parallel studies, DA increased Na+-K+-ATPase activity in cultured rat alveolar epithelial type II cells (ATII). Depolymerization of cellular microtubules by colchicine inhibited the effect of DA on HVT ventilated rats as well as on Na+-K+-ATPase activity in ATII cells. Neither DA nor colchicine affected the short-term Na+-K+-ATPase alpha1- and beta1-subunit mRNA steady-state levels or total alpha1- and beta1-subunit protein abundance in ATII cells. Thus we reason that DA improved alveolar fluid reabsorption in rats ventilated with HVT by upregulating the Na+-K+-ATPase function in alveolar epithelial cells.
Asunto(s)
Cardiotónicos/farmacología , Dopamina/farmacología , Agua Pulmonar Extravascular/metabolismo , Alveolos Pulmonares/metabolismo , Respiración Artificial , Animales , Permeabilidad de la Membrana Celular/efectos de los fármacos , Permeabilidad de la Membrana Celular/fisiología , Activación Enzimática/efectos de los fármacos , Regulación Enzimológica de la Expresión Génica/efectos de los fármacos , Masculino , Alveolos Pulmonares/citología , Alveolos Pulmonares/efectos de los fármacos , ARN Mensajero/análisis , Ratas , Ratas Sprague-Dawley , Mucosa Respiratoria/citología , Mucosa Respiratoria/efectos de los fármacos , Mucosa Respiratoria/metabolismo , ATPasa Intercambiadora de Sodio-Potasio/genética , ATPasa Intercambiadora de Sodio-Potasio/metabolismo , Organismos Libres de Patógenos Específicos , Volumen de Ventilación PulmonarRESUMEN
During hydrostatic pulmonary edema, active Na(+) transport and alveolar fluid reabsorption are decreased. Dopamine (DA) and isoproterenol (ISO) have been shown to increase active Na(+) transport in rat lungs by upregulating Na(+)-K(+)-ATPase in the alveolar epithelium. We studied the effects of DA and ISO in isolated rat lungs with increased left atrial pressure (Pla = 15 cmH(2)O) compared with control rats with normal Pla (Pla = 0). Alveolar fluid reabsorption decreased from control value of 0.51 +/- 0.02 to 0.27 +/- 0.02 ml/h when Pla was increased to 15 cmH(2)O (P < 0.001). DA and ISO increased the alveolar fluid reabsorption back to control levels. Treatment with the D(1) antagonist SCH-23390 inhibited the stimulatory effects of DA (0.30 +/- 0.02 ml/h), whereas fenoldopam, a specific D(1)-receptor agonist, increased alveolar fluid reabsorption in rats exposed to Pla of 15 cmH(2)O (0.47 +/- 0.04 ml/h). Propranolol, a beta-adrenergic-receptor antagonist, blocked the stimulatory effects of ISO; however, it did not affect alveolar fluid reabsorption in control or DA-treated rats. Amiloride (a Na(+) channel blocker) and ouabain (a Na(+)-K(+)-ATPase inhibitor), either alone or together, inhibited the stimulatory effects of DA. Colchicine, which disrupts the cellular microtubular transport of ion-transporting proteins to the plasma membrane, inhibited the stimulatory effects of DA, whereas the isomer beta-lumicolchicine did not block the stimulatory effects of DA. These data suggest that DA and ISO increase alveolar fluid reabsorption in a model of increased Pla by regulating active Na(+) transport in rat alveolar epithelium. The effects of DA and ISO are mediated by the activation of dopaminergic D(1) receptors and the beta-adrenergic receptors, respectively.
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Función del Atrio Izquierdo/fisiología , Dopamina/farmacología , Corazón/fisiopatología , Pulmón/fisiopatología , Edema Pulmonar/fisiopatología , Mucosa Respiratoria/fisiopatología , Amilorida/farmacología , Animales , Función del Atrio Izquierdo/efectos de los fármacos , Líquidos Corporales/efectos de los fármacos , Líquidos Corporales/fisiología , Fenoldopam/farmacología , Corazón/efectos de los fármacos , Corazón/fisiología , Técnicas In Vitro , Isoproterenol/farmacología , Pulmón/efectos de los fármacos , Pulmón/fisiología , Masculino , Ouabaína/farmacología , Perfusión , Propranolol/farmacología , Alveolos Pulmonares/efectos de los fármacos , Alveolos Pulmonares/fisiología , Alveolos Pulmonares/fisiopatología , Ratas , Ratas Sprague-Dawley , Mucosa Respiratoria/efectos de los fármacos , Mucosa Respiratoria/fisiologíaRESUMEN
We studied whether the beta-adrenergic agonist, isoproterenol (ISO), regulates Na,K-ATPase in alveolar epithelial cells (AEC) via a mitogen-activated protein kinase (MAPK)/extracellular signaling related kinase (ERK) dependent pathway. ISO increased ERK activity in AEC by 10 min via a beta-adrenergic receptor, protein kinase A (PKA)-dependent mechanism. Activation of the MAPK pathway by ISO, resulted in increased Na,K-ATPase beta1 and alpha1 subunit protein abundance in whole cell lysates, which resulted in functional Na, K-ATPases at the basolateral membranes. ISO did not change the alpha1 or beta1 mRNA steady state levels, but rapamycin, the inhibitor of the mammalian target of rapamycin, also blocked the ISO-mediated increase in Na,K-ATPase total protein abundance, suggesting a posttranscriptional regulation. We conclude that ISO, regulates the Na,K-ATPase in AEC via PKA, ERK and rapamycin-sensitive mechanisms.
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Isoproterenol/farmacología , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Sirolimus/farmacología , ATPasa Intercambiadora de Sodio-Potasio/metabolismo , Agonistas Adrenérgicos beta/farmacología , Animales , Membrana Celular/metabolismo , Células Cultivadas , Colforsina/farmacología , Proteínas Quinasas Dependientes de AMP Cíclico/antagonistas & inhibidores , Proteínas Quinasas Dependientes de AMP Cíclico/metabolismo , Inhibidores Enzimáticos/farmacología , Células Epiteliales/citología , Células Epiteliales/efectos de los fármacos , Células Epiteliales/enzimología , Masculino , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Propranolol/farmacología , Alveolos Pulmonares/citología , Alveolos Pulmonares/efectos de los fármacos , Alveolos Pulmonares/enzimología , ARN Mensajero/metabolismo , Ratas , Ratas Sprague-Dawley , Transducción de Señal/efectos de los fármacos , ATPasa Intercambiadora de Sodio-Potasio/genéticaRESUMEN
Mechanical ventilation with high tidal volume (HVT) causes lung injury and decreases the lung's ability to clear edema in rats. beta-adrenergic agonists increase active Na(+) transport and lung edema clearance in normal rat lungs by stimulating apical Na(+) channels and basolateral Na,K-ATPase in alveolar epithelial cells. We studied whether beta-adrenergic agonists could restore lung edema clearance in rats ventilated with HVT (40 ml/kg, peak airway pressure of 35 cm H(2)O) for 40 min. The ability of rat lungs to clear edema decreased by approximately 50% after 40 min of HVT ventilation. Terbutaline (TERB) and isoproterenol (ISO) increased lung edema clearance in control nonventilated rats (from 0.50 +/- 0. 02 ml/h to 0.81 +/- 0.04 ml/h and 0.99 +/- 0.05 ml/h, respectively) and restored the lung's ability to clear edema in HVT ventilated rats (from 0.25 +/- 0.03 ml/h to 0.64 +/- 0.02 ml/h and 0.88 +/- 0. 09 ml/h, respectively). Disruption of cell microtubular transport system by colchicine inhibited the stimulatory effects of ISO in HVT ventilated rats, whereas beta-lumicolchicine did not affect beta-adrenergic stimulation. The Na,K-ATPase alpha(1)- and beta(1)-subunit mRNA steady state levels were not affected by incubation with ISO for 60 min in alveolar type II cells isolated from control and HVT ventilated rats. The data suggest that beta-adrenergic agonists increased alveolar fluid reabsorption in rats ventilated with HVT by promoting recruitment of ion-transporting proteins from intracellular pools to the plasma membrane of alveolar epithelial cells.
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Agonistas Adrenérgicos beta/uso terapéutico , Isoproterenol/uso terapéutico , Lesión Pulmonar , Edema Pulmonar/tratamiento farmacológico , Respiración Artificial/efectos adversos , Terbutalina/uso terapéutico , Agonistas Adrenérgicos beta/farmacocinética , Animales , Isoproterenol/farmacocinética , Masculino , Permeabilidad , Edema Pulmonar/etiología , Ratas , Ratas Sprague-Dawley , Mucosa Respiratoria/metabolismo , Terbutalina/farmacocinéticaRESUMEN
The effect of hydrocortisone on platelet activating factor (PAF)-induced pulmonary edema is studied. Thirty four isolated and perfused rabbit lung preparations were used: eight control preparations, eight PAF preparations with two doses of PAF called low dose (LD = 0.5 microg/kg of rabbit weight) and high dose (HD = 1 microg/kg of rabbit weight). Eighteen preparations divided in three groups of six were pretreated with doses of 20, 200 and 2000 mg of hydrocortisone and later given the same doses of PAF as described above. Hydrocortisone significantly decreased (P < 0.05) the effect of PAF LD over the pulmonary arterial pressure (Ppa) in the 200 and 2000 mg groups (58 and 89% decrease, respectively) and it significantly decreased (P < 0.05) the effect of PAF HD over Ppa in all hydrocortisone pretreated groups (48, 70 and 96% decrease, respectively). Fluid filtration rate (FFR) increases mediated by PAF HD were significantly inhibited (P < 0.05) in the 200 and 2000 mg groups (64 and 96% decrease, respectively). We conclude that hydrocortisone inhibits the effect of PAF over the pulmonary circulation.
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Antiinflamatorios/farmacología , Hidrocortisona/farmacología , Factor de Activación Plaquetaria , Edema Pulmonar/inducido químicamente , Animales , Técnicas In Vitro , Respiración con Presión Positiva , Circulación Pulmonar/efectos de los fármacos , ConejosRESUMEN
Platelet activating factor (PAF) has been implicated in the pathophysiology of acute lung injury. The aim of this work is to study the effect of PAF on isolated and perfused rabbit lungs with blood and with a blood-free solution. 24 isolated and perfused rabbit lungs have been used: 8 control preparations (CP), 4 vehicles preparations (VP), 8 PAF preparations (PP) to which we administered PAF (1 microg/Kg of rabbit weight) and 4 acellular preparations (AP) with the same dose of PAF as in PP but dissolved in BSA-Krebs buffer solution. In the preparations pulmonary artery pressure (Ppa), airway pressure (Paw), left atria pressure (Pla) and fluid filtration rate (FFR) were registered. Ppa resulted in a significant difference in AP vs PP, with a value of 21 cm of water (CI 95%: 12-26) vs 205.1 cm of water (CI 95%: 141.3 - 271) respectively. A increase in FFR was observed in PP but it did not occur in AP, the difference being statistically significant: 5.515 g/min (CI 95 %: 2.425 - 8.865) vs 0.049 g/min (CI 95%: 0.008 - 0.32) respectively. Paw was statistically different in PP vs AP, with a value of 14.3 cm of water (CI 95%: 11.57 - 16.7) vs 8.5 cm of water (CI 95%: 8-9) respectively. These results suggest that PAF does not have a direct effect on the endothelium or smooth muscle in the production of lung edema.
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Pulmón/irrigación sanguínea , Factor de Activación Plaquetaria/fisiología , Animales , Sangre , Medio de Cultivo Libre de Suero , Técnicas In Vitro , Conejos , Flujo Sanguíneo Regional/fisiologíaRESUMEN
Exposure of adult rats to 100% O(2) results in lung injury and decreases active sodium transport and lung edema clearance. It has been reported that beta-adrenergic agonists increase lung edema clearance in normal rat lungs by upregulating alveolar epithelial Na(+)-K(+)-ATPase function. This study was designed to examine whether isoproterenol (Iso) affects lung edema clearance in rats exposed to 100% O(2) for 64 h. Active Na(+) transport and lung edema clearance decreased by approximately 44% in rats exposed to acute hyperoxia. Iso (10(-6) M) increased the ability of the lung to clear edema in room-air-breathing rats (from 0.50 +/- 0.02 to 0.99 +/- 0. 05 ml/h) and in rats exposed to 100% O(2) (from 0.28 +/- 0.03 to 0. 86 +/- 0.09 ml/h; P < 0.001). Disruption of intracellular microtubular transport of ion-transporting proteins by colchicine (0. 25 mg/100 g body wt) inhibited the stimulatory effects of Iso in hyperoxia-injured rat lungs, whereas the isomer beta-lumicolchicine, which does not affect microtubular transport, did not inhibit active Na(+) transport stimulated by Iso. Accordingly, Iso restored the lung's ability to clear edema after hyperoxic lung injury, probably by stimulation of the recruitment of ion-transporting proteins (Na(+)-K(+)-ATPase) from intracellular pools to the plasma membrane in rat alveolar epithelium.
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Agonistas Adrenérgicos beta/farmacología , Hiperoxia/complicaciones , Isoproterenol/farmacología , Edema Pulmonar/tratamiento farmacológico , Edema Pulmonar/etiología , Animales , Transporte Biológico Activo/efectos de los fármacos , Proteínas Portadoras/metabolismo , Membrana Celular/metabolismo , Hiperoxia/metabolismo , Pulmón/efectos de los fármacos , Pulmón/metabolismo , Lesión Pulmonar , Masculino , Alveolos Pulmonares/efectos de los fármacos , Alveolos Pulmonares/metabolismo , Edema Pulmonar/metabolismo , Ratas , Ratas Sprague-Dawley , ATPasa Intercambiadora de Sodio-Potasio/metabolismoRESUMEN
Ventilator-associated lung injury (VALI) is caused by high tidal volume (VT) excursions producing microvascular leakage and pulmonary edema. However, the effects of VALI on lung edema clearance and alveolar epithelial cells' Na,K-ATPase function have not been elucidated. We studied lung edema clearance in the isolated-perfused rat lung model after ventilation for 25, 40, and 60 min with high VT (peak airway opening pressure [Pao] of approximately 35 cm H2O) and compared them with low VT ventilation (Pao approximately 8 cm H2O), moderate VT ventilation (Pao approximately 20 cm H2O), and nonventilated rats. Lung edema clearance in control rats was 0.50 +/- 0.02 ml/h and decreased after 40 and 60 min of high VT to 0.26 +/- 0.03 and 0.11 +/- 0.08 ml/h, respectively (p < 0.01), but did not change after low VT and moderate VT ventilation at any time point. Lung permeability to small (22Na+, [3H]mannitol) and large solutes (fluorescein isothiocyanate-tagged albumin [FITC-albumin]) increased significantly in rats ventilated for 60 min with high VT, compared with low VT, moderate VT, and control rats (p < 0.01). Paralleling the impairment in lung edema clearance we found a decrease in Na,K-ATPase activity in alveolar type II (ATII) cells isolated from rats ventilated with moderate VT and high VT for 40 min without changes in alpha1 Na,K-ATPase mRNA. We reason that VALI decreases lung ability to clear edema by inhibiting active sodium transport and Na,K-ATPase function in the alveolar epithelium.
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Ventilación de Alta Frecuencia/efectos adversos , Edema Pulmonar/fisiopatología , Síndrome de Dificultad Respiratoria/fisiopatología , Animales , Modelos Animales de Enfermedad , Fluoresceína-5-Isotiocianato/farmacocinética , Colorantes Fluorescentes/farmacocinética , Técnicas In Vitro , Pulmón/metabolismo , Pulmón/fisiopatología , Macrófagos Alveolares/enzimología , Masculino , Permeabilidad , Edema Pulmonar/etiología , Edema Pulmonar/metabolismo , ARN Mensajero/análisis , Ratas , Ratas Sprague-Dawley , Síndrome de Dificultad Respiratoria/complicaciones , Síndrome de Dificultad Respiratoria/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Canales de Sodio/metabolismo , ATPasa Intercambiadora de Sodio-Potasio/genética , ATPasa Intercambiadora de Sodio-Potasio/metabolismo , Volumen de Ventilación PulmonarRESUMEN
Exposure to hyperoxia causes lung injury, decreases active sodium transport and lung edema clearance in rats. Dopamine (DA) increases lung edema clearance by stimulating vectorial Na+ flux and Na, K-ATPase function in rat alveolar epithelium. This study was designed to test whether DA (10(-)5 M) would increase lung edema clearance in rats exposed to 100% O2 for 64 h. Active Na+ transport and lung edema clearance decreased by approximately 44% in rats exposed to acute hyperoxia (p < 0.001). DA increased lung edema clearance in room air breathing rats (from 0.50 +/- 0.02 to 0.75 +/- 0.06 ml/h) and in rats exposed to 100% O2 (from 0.28 +/- 0.03 to 0. 67 +/- 0.03 ml/h). Disruption of cell microtubular transport system by colchicine blocked the stimulatory effect of DA on active Na+ transport in control and hyperoxic rats, whereas the isomer beta-lumicolchicine, which does not affect cell microtubular transport, did not inhibit the stimulatory effects of dopamine. The Na,K-ATPase alpha1-subunit protein abundance increased in the basolateral membranes of alveolar type II (ATII) cells incubated with 10(-)5 M DA for 15 min, probably by recruiting Na+ pumps from intracellular pools. Colchicine, but not beta-lumicolchicine, prevented the recruitment of alpha1 subunits to the plasma membrane by DA. Accordingly, DA restored lung ability to clear edema in hyperoxic-injured rat lungs. Conceivably, dopamine induces recruitment of Na+ pumps from intracellular pools to the plasma membrane of alveolar epithelial cells and thus increases lung edema clearance.
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Dopamina/uso terapéutico , Hiperoxia/complicaciones , Edema Pulmonar/tratamiento farmacológico , Enfermedad Aguda , Animales , Permeabilidad de la Membrana Celular/efectos de los fármacos , Células Cultivadas , Colchicina/farmacología , Modelos Animales de Enfermedad , Epitelio/efectos de los fármacos , Epitelio/metabolismo , Fluoresceína-5-Isotiocianato/farmacocinética , Colorantes Fluorescentes/farmacocinética , Hiperoxia/metabolismo , Líquido Intracelular/metabolismo , Transporte Iónico/efectos de los fármacos , Macrófagos Alveolares/efectos de los fármacos , Macrófagos Alveolares/metabolismo , Macrófagos Alveolares/patología , Masculino , Edema Pulmonar/etiología , Edema Pulmonar/metabolismo , Ratas , Ratas Sprague-Dawley , Canales de Sodio/efectos de los fármacos , Canales de Sodio/metabolismo , ATPasa Intercambiadora de Sodio-Potasio/metabolismoRESUMEN
It is well known that scorpion venom induces lung lesions and respiratory distress which are usually classified as pulmonary oedema (PO). Tityus discrepans is a scorpion that lives in the north-central area of Venezuela, is the most common source of human envenomation here and produces PO. We studied the action of the venom of Tityus discrepans on whole rabbits and on their isolated lungs perfused with Krebs saline with 1 g/l of bovine serum albumin (Krebs-BSA saline). Two milligram of venom were diluted in 250 ml of solution (approximately the rabbit's total blood volume) and used to perfuse isolated lungs. Lung oedema occurred in rabbits which received 1 mg/kg of scorpion venom i.p., heparin prevented the production of this lung oedema. T. discrepans venom produced PO, in rabbits pretreated with 15 mg/kg of ajoene. Yet, Tityus venom had no effects on isolated lungs perfused with citrated or heparinized blood, and in lungs perfused with Krebs-BSA with normal Ca2+. These result show that Tityus venom does not act directly on lungs. Otherwise, we have observed that abundant microthrombi occurred in all rabbit lungs exposed to venom in vivo, suggesting that these clotting alterations are fundamental to produce PO. The presence of intravascular microthrombi is not characteristic of the usual PO hinting that scorpion venom induced pulmonary alterations are a different clinical entity. We thus propose that the use of the term pulmonary oedema in scorpionism should abandoned in favor of scorpion venom respiratory distress syndrome.
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Síndrome de Dificultad Respiratoria del Recién Nacido/inducido químicamente , Venenos de Escorpión/toxicidad , Presión del Aire , Animales , Presión Sanguínea , Líquido del Lavado Bronquioalveolar , Humanos , Técnicas In Vitro , Recién Nacido , Pulmón/patología , Pulmón/fisiopatología , Masculino , Arteria Pulmonar/fisiología , Edema Pulmonar/inducido químicamente , Edema Pulmonar/patología , Edema Pulmonar/fisiopatología , Conejos , Síndrome de Dificultad Respiratoria del Recién Nacido/patología , Síndrome de Dificultad Respiratoria del Recién Nacido/fisiopatologíaRESUMEN
We have studied the effects of fenoterol on PAF-induced response in pulmonary circulation. We used 28 isolated and perfused rabbit lungs preparations: eight control preparations (CP), four vehicles preparations (VP), eight PAF preparations (PP) with two doses of PAF, one called low dose (LD = 0.5 microg/kg of weight) and the other high dose (HD = 1 microg/kg of weight) and eight Fenoterol preparations (FP) which we administered 0.05 mg of Fenoterol for 15 min, followed by a LD and HD of PAF. FP prevented elevation of pulmonary artery pressure (Ppa) as compared to PP, at LD of PAF: 12.615 (CI 95%: 8.57-20.885) versus 83.705 (CI 95%: 50.55-114.3) cm of water; and at HD of PAF: 19.38 (CI 95%: 11.235-28.94) versus 205.1 (CI 95%: 141.3-271) cm of water respectively. FP prevented the increase in fluid filtration rate (FFR) observed in PP at both doses of PAF LD: 0.765 (CI 95%: 0.07-3.385) versus 0.01 (CI 95%: -0.05-0.005) g/min; HD: 5.515 (CI 95%: 2.425-8.865) versus 0.03 (CI 95%: 0-0.33) g/min. Our results suggest that PAF has a vasoconstrictor effect that produces lung edema and this effect is inhibited by fenoterol.
Asunto(s)
Agonistas Adrenérgicos beta/farmacología , Fenoterol/farmacología , Factor de Activación Plaquetaria , Edema Pulmonar/inducido químicamente , Edema Pulmonar/fisiopatología , Animales , Técnicas In Vitro , Perfusión , Circulación Pulmonar/efectos de los fármacos , ConejosRESUMEN
The isolated perfused rat lung model (IL) is used to study alveolar epithelial transport properties. Most of the previous studies have been done over a short period of time and have not used the same preparation as a control and intervention group. We evaluated whether the IL preparation could be used for a prolonged period of time (5 h) and studied the rates of active Na+ transport, lung liquid clearance, and passive movement of solutes. Active Na+ transport and lung liquid clearance were stable from 1 to 5 h. The passive movement of small solutes (Na+, mannitol) did not change significantly, and albumin movement increased slightly at the fifth hour. Total RNA isolated from IL after 5 h was intact, and the Na+-K+-ATPase activity in alveolar type II cells isolated at the end of 5-h experiments was equal to Na+-K+-ATPase function from freshly isolated alveolar type II cells. Finally, we measured the stimulatory effect of the beta-adrenergic-agonist terbutaline and the inhibitory effect of the Na+-K+-ATPase-antagonist ouabain by using the same animal as a control. Accordingly, the isolated perfused lung model is functionally stable for at least 5 h, and it could be utilized to evaluate the effect of different interventions by using the same preparation.
Asunto(s)
Pulmón/fisiología , Modelos Biológicos , Alveolos Pulmonares/fisiología , Animales , Transporte Biológico , Transporte Biológico Activo , Células Epiteliales/fisiología , Técnicas In Vitro , Cinética , Masculino , Manitol/farmacocinética , Matemática , Perfusión , Ratas , Ratas Sprague-Dawley , Sodio/metabolismo , Soluciones , Factores de TiempoRESUMEN
INTRODUCTION AND OBJECTIVES: Because left ventricular mass is associated with an increase in the risk of morbidity and mortality of cardiovascular diseases in the general population having the electrocardiogram as an accessible and inexpensive method for the diagnosis of left ventricular hypertrophy, we decided to calculate the sensitivity and specificity of 5 electrocardiographic criteria for the diagnosis of left ventricular hypertrophy and to compare the results of the original authors to ours. PATIENTS AND METHODS: 135 patients were evaluated; 46 patients were excluded by the following criteria: chronic obstructive pulmonary disease, complete left or right bundle branch block, cardiovascular ischemic disease or Wolf-Parkinson-White Syndrome. 89 patients remained and had an electrocardiogram performed applying the following criteria: Romhilt-Estes Point-Score system. Sokolow-Lyon (SV1 + RV5 or V6 > 3.5 mV) and (RaVL > 1.1 mV), Cornell and Rodríguez Padial. Left ventricular hypertrophy was defined by the Penn Convention Criteria. RESULTS: In our study we obtained the following results: a) Romhilt-Estes had a sensitivity of 12% and a specificity of 87%; b) Sokolow-Lyon (SV1 + RV5 or V6) had a sensitivity of 22% and a specificity of 79%; c) Sokolow-Lyon (RaVL) has a sensitivity of 18% and a specificity of 92%; d) Cornel had a sensitivity of 31% and a specificity of 87%, and e) Rodríguez Padial had a sensitivity of 82% and a specificity of 8%. There are similarities between our results and the authors's original ones. However, there are significant statistical differences between them (p < or = 0.01). CONCLUSION: Our conclusion is that these criteria have a low diagnostic value in the isolated interpretation of patients with left ventricular hypertrophy, and we need to integrate them with the whole medical history and physical examination.