RESUMEN

Acute respiratory distress syndrome (ARDS) is associated with significant morbidity and mortality. The pathophysiology of ARDS includes abnormalities of surfactant function as well as pulmonary inflammation. Immunomodulating drugs, like Lidocaine, have shown some success in decreasing inflammation in ARDS. We attempted to combine surfactant lavage's ability to reverse the surfactant dysfunction, while acting as a vehicle to deliver Lidocaine. Gravity-driven surfactant (Infasurf) lavage (35 ml/kg) was administered alone or mixed with Lidocaine after severe HCl acid injury (0.3 N; 3 cc/kg) in neonatal piglets. Treatment groups included: control (C) ( n = 5), surfactant lavage (SL) (35 ml/kg-diluted Infasurf) ( n = 7) and SL mixed with Lidocaine (SL+L) ( n = 7). About 26-27% of the lavage was retained (phospholipid 73-74 mg/kg; Lidocaine 1.8 mg/kg). Oxygenation progressively increased in the SL and SL+L groups over the 4-hour period (at 240 min: C = 99 +/- 14; SL = 154 +/- 39; SL+L = 230 +/- 40 mmHg) ( p < 0.05). PaCO(2) increased in all groups from 43 +/- 0.3 to 55 +/- 0.7 mmHg. Only SL+L showed a reduction in PaCO(2) (at 240 min: C = 54 +/- 4; SL = 53 +/- 7; SL+L = 49 +/- 2 mmHg) ( p < 0.05). Finally, SL and SL + L had superior characteristics during the quasi-static pressure volume (PV) procedure as compared to Control ( p < 0.05). In our HCl ALI model, SL improved oxygenation and quasi-static lung compliance over C. The pulmonary function effects of SL were further enhanced by the addition of Lidocaine to the surfactant suspension. Combining therapeutic agents with surfactant lavage may be an effective strategy in ALI.

Asunto(s)

Adyuvantes Inmunológicos/administración & dosificación , Lavado Broncoalveolar/métodos , Lidocaína/administración & dosificación , Pulmón/efectos de los fármacos , Surfactantes Pulmonares/administración & dosificación , Síndrome de Dificultad Respiratoria/tratamiento farmacológico , Animales , Modelos Animales de Enfermedad , Quimioterapia Combinada , Femenino , Ácido Clorhídrico , Pulmón/fisiología , Masculino , Valores de Referencia , Síndrome de Dificultad Respiratoria/inducido químicamente , Síndrome de Dificultad Respiratoria/patología , Pruebas de Función Respiratoria , Tensión Superficial/efectos de los fármacos , Porcinos

RESUMEN

OBJECTIVE: To compare low-cost, off-the-shelf technology for digitizing pediatric chest radiographs. MATERIALS AND METHODS: Forty pediatric chest radiographs (hard copy), each with a single abnormality, were digitized using a commercial film digitizer and two low-cost METHODS: a digital camera and a flatbed scanner. A stratified, randomized, block design was used where 20 readers evaluated 40 different images to determine the ability to accurately detect the abnormality. Readers then rated all 160 images (40 images x 4 methods) for conspicuity of the abnormality and overall image quality. RESULTS: Abnormalities were correctly identified on 82.3 % of hard copy images, 82.9 % of flatbed scanner images, 74.3 % of film digitizer images, and 69.7 % of digital camera images (p < 0.05) when compared to hard copy or flatbed scanner images. Lesion conspicuity was rated higher on hard copy (p < 0.05) than all digitized images. Conspicuity ratings were similar for flatbed scanner and film digitizer images, but lower in digital camera images (p < 0.05). For overall image quality, all were rated significantly different from each other (p < 0.05), with hard copy > flatbed scanner > film digitizer > digital camera images. CONCLUSION: A low-cost flatbed scanner yielded digital pediatric chest images which were significantly superior to digital camera images While flatbed scanner images were interpreted with the equivalent diagnostic accuracy of hard copy images, they were rated lower for image quality and lesion conspicuity.

Asunto(s)

Intensificación de Imagen Radiográfica/métodos , Telerradiología/economía , Adolescente , Niño , Preescolar , Redes de Comunicación de Computadores , Humanos , Lactante , Recién Nacido , Intensificación de Imagen Radiográfica/economía , Sistemas de Información Radiológica/economía , Telerradiología/instrumentación

RESUMEN

PURPOSE: We postulate that computer keyboards and faucet handles are significant reservoirs of nosocomial pathogens in the intensive care unit (ICU) setting. METHODS: Sterile swab samples were obtained from 10 keyboards and 8 pairs of faucet handles in the medical ICU at Tripler Army Medical Center during a period of 2 months. Methicillin-resistant Staphylococcus aureus (MRSA) obtained from the environmental and patient specimens were sent for DNA identification by using pulsed-field gel electrophoresis. RESULTS: A total of 144 samples were obtained (80 keyboards and 64 faucet handles), yielding 33 isolates. The colonization rate for keyboards was 24% for all rooms and 26% in occupied rooms. Rates for faucet handles in all rooms and occupied rooms were 11% and 15%, respectively. The environmental isolates annd their prevalence were: MRS, 49%; Enterococcus, 18%; Enterobacter, 12%; and all other gram-negative rods, 21%. Fourteen individual patient isolates were recorded: MRSA, 43%; Enterobacter, 21%; other gram-negative rods, 36%; and Enterococcus, 0%. By using pulsed-field gel electrophoresis, an indistinguishable strain of MRSA was identified in two patients, the keyboards and faucet handles in their respective rooms, and on other keyboards throughout the ICU, including the doctors' station. CONCLUSIONS: The colonization rate for keyboards and faucet handles, novel and unrecognized fomites, is greater than that of other well-studied ICU surfaces in rooms with patients positive for MRSA. Our findings suggest an associated pattern of environmental contamination and patient infection, not limited to the patient's room. Pulsed-field gel electrophoresis results have documented an indistinguishable strain of MRSA present as an environmental contaminant on these two fomites and in two patients with clinical infections patients during the same period. We believe these findings add evidence to support the hypothesis that these particular surfaces may serve as reservoirs of nosocomial pathogens and vectors for cross-transmission in the ICU setting. New infection control policies and engineering plans were initiated on the basis of our results.

Asunto(s)

Infección Hospitalaria/microbiología , Infección Hospitalaria/transmisión , Reservorios de Enfermedades , Infecciones por Enterobacteriaceae/microbiología , Infecciones por Enterobacteriaceae/transmisión , Enterococcus , Contaminación de Equipos , Infecciones por Bacterias Grampositivas/microbiología , Infecciones por Bacterias Grampositivas/transmisión , Unidades de Cuidados Intensivos , Resistencia a la Meticilina , Infecciones Estafilocócicas/microbiología , Infecciones Estafilocócicas/transmisión , Staphylococcus aureus , Infección Hospitalaria/prevención & control , Reservorios de Enfermedades/estadística & datos numéricos , Electroforesis en Gel de Campo Pulsado , Infecciones por Enterobacteriaceae/prevención & control , Monitoreo del Ambiente/métodos , Monitoreo Epidemiológico , Contaminación de Equipos/prevención & control , Contaminación de Equipos/estadística & datos numéricos , Infecciones por Bacterias Grampositivas/prevención & control , Hawaii/epidemiología , Hospitales Militares , Humanos , Control de Infecciones/métodos , Microcomputadores , Prevalencia , Factores de Riesgo , Ingeniería Sanitaria/instrumentación , Serotipificación , Infecciones Estafilocócicas/prevención & control

RESUMEN

This study tested the hypothesis that inhaled nitric oxide (NO) and combined NO and hyperoxia will result in less pulmonary dysfunction and delay onset of respiratory signs compared with hyperoxia-exposed newborn guinea pigs (GPs). GPs were exposed to room air (n = 14), 95% O(2) (n = 36), 20 parts per million (ppm) NO (n = 14), or combined 20 ppm NO and 95% O(2) (NO/O(2), n = 13) for up to 5 days. Data evaluated included latency interval for onset of respiratory distress, pressure volume curves, lung histology, and bronchoalveolar lavage (BAL) polymorphonuclear cells (PMNs), proteolytic activity, and total protein. NO-exposed GPs did not develop respiratory distress and had no evidence of pulmonary dysfunction. O(2)-exposed GPs developed respiratory distress after 1-5 days (median 4.0) vs. 3-5 days (median 5.0) for NO/O(2) exposure (P < 0.05). BAL from O(2)-exposed GPs showed increased PMNs compared with NO/O(2)-exposed GPs. O(2)- and NO/O(2)-exposed GPs had comparable reduced lung volumes, lung histology, and increased BAL proteinase activity and total protein. In summary 1) O(2) exposure resulted in multiple measures of pulmonary dysfunction in newborn GPs, 2) 5-day exposure to NO produced no noticeable respiratory effects and pulmonary dysfunction, and 3) short-term exposure (

Asunto(s)

Animales Recién Nacidos/fisiología , Hiperoxia/complicaciones , Enfermedades Pulmonares/prevención & control , Óxido Nítrico/administración & dosificación , Administración por Inhalación , Animales , Líquido del Lavado Bronquioalveolar/química , Líquido del Lavado Bronquioalveolar/citología , Quimotripsina/metabolismo , Cobayas , Recuento de Leucocitos , Pulmón/patología , Pulmón/fisiopatología , Enfermedades Pulmonares/etiología , Enfermedades Pulmonares/patología , Mediciones del Volumen Pulmonar , Neutrófilos , Oxígeno/administración & dosificación , Tripsina/metabolismo

RESUMEN

In an acute lung injury model, we previously observed reversal of pulmonary dysfunction with natural surfactant administered by lavage (dose = 18 mg/kg phospholipid). The present study questioned whether a lower dose of phospholipid would be effective if a recombinant preparation rather than natural surfactant were used. Acute lung injury was induced by repeated saline lung lavage in ventilated, sedated, and paralyzed piglets. Three concentrations of recombinant surfactant were studied (low phospholipid, 1 mg/mL; medium phospholipid, 4 mg/mL; high phospholipid, 13.5 mg/mL). Control piglets received no surfactant. Thirty-five milliliters per kilogram of surfactant was administered by gravity, followed by passive drainage of excess fluid. All treatment groups retained similar volumes (4.7+/-0.3 mL/ kg), corresponding to phospholipid doses of 4+/-0.4, 22+/-3, and 67+/-4 mg/kg in low, medium, and high-dose groups, respectively. Treatment groups showed significant improvement in Pao2 compared with controls. Other parameters different from controls were found in only the medium and high-dose groups. All surfactant-treated groups showed improvement over time in Pao2, Paco2, lung resistance mean airway pressure, functional residual capacity, and dynamic compliance. These data support the statement that whereas there is a dose response to exogenous surfactant, the effective dose of recombinant surfactant in acute lung injury may be as low as 4 mg/kg phospholipid when administered by lavage.

Asunto(s)

Lesión Pulmonar , Tensoactivos/uso terapéutico , Enfermedades de los Porcinos/terapia , Animales , Lavado Broncoalveolar , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/uso terapéutico , Pruebas de Función Respiratoria , Tensoactivos/administración & dosificación , Porcinos

RESUMEN

Exogenous surfactant therapy is not standard in the acute respiratory distress syndrome (ARDS) because of a lack of proven benefit. Nonuniform surfactant distribution after either bolus or aerosol administration may be an important factor limiting response. In a previous study of acute lung injury, we demonstrated that lavage administration of Exosurf (13.5 mg phospholipid/ml) was both effective and distributed uniformly in the lungs. Since the endogenous surfactant pool is much smaller than the typical dose of exogenous surfactant administered, we hypothesized that dilute surfactant preparations (4-4.5 mg phospholipid/ml) administered by lung lavage would be equally effective in reversing pulmonary dysfunction in a piglet model of acute lung injury. We compared three dilute surfactants: Infasurf (n = 5), KL4-Surfactant (n = 6), and Exosurf (n = 5) with controls (n = 6) and undiluted Exosurf (13. 5 mg phospholipid/ml; n = 6). All dilute surfactant preparations were effective in improving oxygenation and other parameters of pulmonary function. Surfactant administered by lavage resulted in uniform lung distribution. We conclude that dilute surfactants administered by lung lavage are effective in reversing pulmonary dysfunction after acute lung injury. We speculate that doses in the range of 20-40 mg phospholipid/kg may be adequate to improve lung function in ARDS when exogenously administered surfactant is uniformly distributed in the lung.

Asunto(s)

Enfermedades Pulmonares/tratamiento farmacológico , Fosforilcolina , Surfactantes Pulmonares/administración & dosificación , Animales , Animales Recién Nacidos , Lavado Broncoalveolar , Modelos Animales de Enfermedad , Combinación de Medicamentos , Alcoholes Grasos/administración & dosificación , Alcoholes Grasos/uso terapéutico , Péptidos y Proteínas de Señalización Intercelular , Péptidos/administración & dosificación , Péptidos/uso terapéutico , Polietilenglicoles/administración & dosificación , Polietilenglicoles/uso terapéutico , Surfactantes Pulmonares/uso terapéutico , Síndrome de Dificultad Respiratoria , Porcinos

RESUMEN

Despite evidence of surfactant dysfunction in the acute respiratory distress syndrome (ARDS), treatment with exogenous surfactant remains experimental. Uneven pulmonary distribution is one factor that may limit response. We investigated whether exogenous surfactant administered by lavage, consisting of a 35 ml/kg volume instilled by gravity and followed immediately by passive drainage (LAVAGE), would result in better lung distribution and physiologic response than with surfactant administered as a 5 ml/kg bolus (BOLUS). Exosurf, an artificial surfactant, was administered after acute lung injury induced by saline lung lavage in neonatal piglets. In the LAVAGE group (n= 9), 10.1 +/- 0.4 ml/kg of surfactant was retained, corresponding to a phospholipid dose of 136 +/- 5 mg/kg. In the BOLUS group (n = 9), the dose administered was 203 mg/kg phospholipid. Piglets in the LAVAGE group demonstrated greater improvement in pulmonary function, including PaO2, PaCO2, ventilation efficiency index, functional residual capacity (FRC), and pressure-volume curves than piglets in the BOLUS group. Some differences were found in lung distribution of surfactant. We conclude that Exosurf is more effective when administered by lavage in this lung injury model. We speculate that the lavage method of administration holds promise as an alternative method of surfactant administration in patients with ARDS.

Asunto(s)

Alcoholes Grasos/farmacología , Lesión Pulmonar , Pulmón/fisiopatología , Fosforilcolina , Polietilenglicoles/farmacología , Surfactantes Pulmonares/farmacología , Enfermedad Aguda , Animales , Animales Recién Nacidos , Combinación de Medicamentos , Alcoholes Grasos/administración & dosificación , Alcoholes Grasos/farmacocinética , Femenino , Inyecciones , Pulmón/metabolismo , Masculino , Polietilenglicoles/administración & dosificación , Polietilenglicoles/farmacocinética , Surfactantes Pulmonares/administración & dosificación , Surfactantes Pulmonares/farmacocinética , Porcinos , Irrigación Terapéutica , Factores de Tiempo , Distribución Tisular

RESUMEN

Evidence for surfactant dysfunction in acute respiratory distress syndrome (ARDS) suggests a role for exogenous surfactant which contains apoprotein for resistance to protein inhibition. We compared the effects of KL-4-Surfactant, an artificial preparation containing a synthetic 21 amino acid peptide with SP-B-like activity, with Exosurf, an artificial protein-free surfactant, and Survanta, a bovine protein-containing surfactant, in a saline lung lavage model of ARDS in neonatal piglets. Two sequential series of lung lavages were performed to lower PaO2 < 100 mm Hg, each followed by administration of surfactant or air and a 90-min observation period. Progressive lung injury was demonstrated by deterioration in pulmonary function, increasing bronchoalveolar lavage protein, and changes in histopathology. All surfactants improved oxygenation, although oxygenation was generally better with Survanta and KL-4-Surfactant. Further, Survanta and KL-4-Surfactant groups showed improvement in ventilation, with decreases in PaCO2 and increases in FRC. Only KL-4-Surfactant demonstrated greater pressure-volume characteristics and lower bronchoalveolar protein than those of Controls. We conclude that the physiologic effects of KL-4-Surfactant are more like Survanta in this model. We speculate that KL-4-Surfactant may improve pulmonary function, reduce alveolar protein leak, and thus be efficacious in the treatment of ARDS.

Asunto(s)

Productos Biológicos , Fosforilcolina , Surfactantes Pulmonares/uso terapéutico , Síndrome de Dificultad Respiratoria/tratamiento farmacológico , Animales , Animales Recién Nacidos , Líquido del Lavado Bronquioalveolar/química , Líquido del Lavado Bronquioalveolar/citología , Combinación de Medicamentos , Alcoholes Grasos/uso terapéutico , Capacidad Residual Funcional , Péptidos y Proteínas de Señalización Intercelular , Pulmón/patología , Péptidos/uso terapéutico , Polietilenglicoles/uso terapéutico , Síndrome de Dificultad Respiratoria/patología , Síndrome de Dificultad Respiratoria/fisiopatología , Mecánica Respiratoria , Porcinos

RESUMEN

The newborn piglet is becoming increasingly popular as a model for neonatal studies. However, data on normal physiologic baseline values and the influence of anesthesia on these values are scarce. In this study, we describe husbandry, surgical, and experimental methods used to establish a conscious, chronically catheterized neonatal piglet model, which enabled study of unrestrained piglets recovered from surgery and anesthesia, for up to 10 days after separation from the sow. Chronic catheterization allowed repeated experiments to be performed in the same animals, reducing the number of animals needed for study. Presented herein are baseline resting hemodynamic and blood chemistry data and circulating hormone measurements of vasopressin, plasma renin activity, adrenocorticotrophic hormone, cortisol, epinephrine, norepinephrine, and dopamine for piglets in the first 2 weeks of life. Also, in two series of experiments, the effects of the gas anesthetic isoflurane and the injectable anesthetic pentobarbital on these baseline values were investigated. Results indicate that both pentobarbital and isoflurane elicit changes in blood pressure, heart rate, vasopressin, plasma renin activity and ventilatory drive that should be considered when using either of these anesthetic agents in acute studies.

Asunto(s)

Anestesia , Animales Recién Nacidos/fisiología , Hemodinámica/efectos de los fármacos , Hormonas/sangre , Isoflurano/farmacología , Pentobarbital/farmacología , Porcinos/fisiología , Hormona Adrenocorticotrópica/sangre , Animales , Presión Sanguínea/efectos de los fármacos , Dopamina/sangre , Epinefrina/sangre , Femenino , Frecuencia Cardíaca/efectos de los fármacos , Hidrocortisona/sangre , Masculino , Norepinefrina/sangre , Valores de Referencia , Renina/sangre , Vasopresinas/sangre

RESUMEN

We studied different sequences of lung inflation in ventilated newborn piglets with normal lungs in order to determine the effects of sequence, magnitude and duration of distending pressure on pulmonary function, and/or hemodynamics. End-expiratory pressure was varied using a continuous negative extrathoracic pressure (CNEP) device. Three groups of ventilated piglets with normal lungs were exposed to 2 cmH2O increments of CNEP from -2 to -12 cmH2O, and to decrements from -12 to -2 cmH2O, or to only -6 cmH2O. Lung inflation sequence, magnitude of inflation pressure, and duration of inflation had significant effects on end-expiratory lung volume and lung compliance at numerically equivalent pressure levels. End-expiratory lung volume and lung compliance varied (at four and five of six inflation pressures studied) by as much as 68% and 104%, respectively. Hemodynamic effects of the lung inflation sequence were more variable; those found to be different at numerically equivalent pressure levels were associated with changes in lung compliance and ventilation. Differences in pulmonary mechanics can best be explained by the effects of lung inflation on alveolar recruitment versus overinflation.

Asunto(s)

Pulmón/fisiología , Respiración Artificial , Animales , Animales Recién Nacidos , Femenino , Rendimiento Pulmonar/fisiología , Mediciones del Volumen Pulmonar , Masculino , Presión , Circulación Pulmonar/fisiología , Porcinos

RESUMEN

To determine renal function throughout development of hypertension in the spontaneously hypertensive rat (SHR) and its normotensive counterpart, the Wistar-Kyoto rat (WKY), renal clearance studies were performed at 2-wk intervals from 4 to 12 wk and again at 16 wk of age in conscious chronically instrumented rats after recovery (4-6 days) from surgery. The data indicate that the critical period for the development of hypertension in SHR was between 4 and 6 wk of age. Mean arterial pressure sharply increased from 107 +/- 5 (n = 6) to 145 +/- 6 mmHg (n = 6) between 4 and 6 wk of age, did not change between 6 and 10 wk of age, and gradually rose between 10 and 16 wk of age to 183 +/- 3 mmHg. In WKYs, blood pressure increased only slightly from 97 +/- 3 mmHg at 4 wk of age (n = 8) to 110 +/- 3 mmHg at 8 wk of age (n = 8), where it remained through adulthood. Glomerular filtration rate (GFR) in the 4-wk-old SHR was significantly decreased compared with WKY (0.94 +/- 0.03 vs. 1.11 +/- 0.04 ml.min-1 x g wet kidney wt-1), and it recovered to normal level and stabilized by 6 wk of age (1.14 +/- 0.04 ml.min-1 x g wet kidney wt-1). Renal blood flow was lower in the SHR only at 4 and 16 wk; it increased with age in both groups. Renal vascular resistance was higher in the SHR at 4 wk and remained elevated throughout the observation period.(ABSTRACT TRUNCATED AT 250 WORDS)

Asunto(s)

Hipertensión/fisiopatología , Riñón/fisiopatología , Animales , Animales Recién Nacidos/crecimiento & desarrollo , Presión Sanguínea , Peso Corporal , Tasa de Filtración Glomerular , Hipertensión/orina , Riñón/crecimiento & desarrollo , Masculino , Concentración Osmolar , Ratas , Ratas Endogámicas SHR , Ratas Endogámicas WKY , Circulación Renal

RESUMEN

Over the past decade several new routes of neurohypophysial hormone metabolism have been identified. These include nonhepatic splanchnic clearance and renal clearance in addition to filtration that appears to be receptor mediated. The intraluminal degradation of VP in the proximal tubule, and distal tubular secretion, at least in one species, has been identified. The brain has been identified as a site for VP and OT metabolism, and the amniotic sac may be a major site for VP clearance in the guinea pig fetus. There have been generalized findings regarding VP and OT metabolism. First, VP metabolism in the whole body and in the amniotic sac appears to increase with increasing concentrations of hormone; this does not appear to be the case with OT. Also, evidence has been presented that suggests a potential for the formation of biologically active metabolites. There have been several associations of pathophysiological states with altered VP or OT metabolism, sometimes with plasma levels remaining unchanged. Lastly, caution is emphasized when measuring these hormones by RIA, and differences in specificities of antisera toward hormone metabolites must be considered.

Asunto(s)

Hormonas Neurohipofisarias/metabolismo , Animales , Femenino , Humanos , Hipertensión/metabolismo , Técnicas Inmunológicas , Concentración Osmolar , Oxitocina/metabolismo , Hormonas Neurohipofisarias/fisiología , Embarazo , Complicaciones del Embarazo/metabolismo , Vasopresinas/metabolismo

RESUMEN

To determine whether altered airway smooth muscle contractility contributes to airway hyperreactivity resulting from hyperoxic exposure, in vitro contractile responses of airways to two physiological constrictors, acetylcholine (10(-9) to 10(-4) M) and histamine (10(-8) to 10(-4) M), were examined. Extrathoracic trachea, intrathoracic trachea, and bronchus from 1- to 2-day-old (newborn) guinea pigs exposed to 85% oxygen for 84 h were compared with tissues obtained from newborns reared in room air. Responses in the presence and absence of aspirin (ASA; 10(-3) M) were compared. Hyperoxic exposure did not affect the histology of the airway epithelia. Contractile responses to acetylcholine and histamine were similar. Without ASA, maximal tensions generated were higher in both extrathoracic and intrathoracic trachea obtained from hyperoxia-exposed neonates than in trachea from newborns reared in room air. ASA caused maximal tensions of trachea from newborns reared in room air to increase but did not affect the already increased contractility of trachea from hyperoxia-exposed animals; the tensions achieved in hyperoxic tissues with and without ASA were similar to the hyperactive responses induced by ASA in tissues from animals reared in room air. Bronchi showed responses similar to those seen in tracheal segments. Thus, despite no apparent histological effect on the airway epithelium, hyperoxic exposure seems to increase airway smooth muscle contractility, is nonspecific for different constricting agents, and shows no regional differences in airway reactivity.

Asunto(s)

Bronquios/efectos de los fármacos , Oxígeno/toxicidad , Tráquea/efectos de los fármacos , Acetilcolina/farmacología , Animales , Animales Recién Nacidos , Aspirina/farmacología , Bronquios/patología , Bronquios/fisiopatología , Displasia Broncopulmonar/etiología , Femenino , Cobayas , Histamina/farmacología , Humanos , Técnicas In Vitro , Recién Nacido , Masculino , Contracción Muscular/efectos de los fármacos , Contracción Muscular/fisiología , Músculos Respiratorios/efectos de los fármacos , Músculos Respiratorios/fisiopatología , Tráquea/patología , Tráquea/fisiopatología

RESUMEN

Dihydropyridine calcium agonists affect airway smooth muscle function by modulating the voltage-dependent calcium channel. Two such agonists, BAY K 8644 and CGP 28392 increase airway smooth muscle tone in adult guinea pigs but their actions during ontogeny are unknown. We compared contractile responses of airway tissue from fetal, newborn and young adult guinea pigs to cumulative doses of both BAY K 8644 and CGP 28392 under isometric conditions in vitro. Responses were examined in the presence and absence of aspirin to determine if endogenous cyclooxygenase products modulated these effects. BAY K 8644 generated a contractile response in 85 of 86 tissues. Maximum contraction was greater in extrathoracic tracheas from newborns when compared to adults (P < .05). In fetuses and newborns, contraction overall was greater in the presence of aspirin; however, in adult airways cyclooxygenase blockade did not appear to have any effect (P < .05). In contrast, CGP 28392 produced no contraction in 14 of 19 tracheas (all ages combined) in the presence of aspirin; whereas, all 18 tracheas in the absence of aspirin contracted. Also, there were no significant differences in maximum response among these age groups or tissue types to CGP 28392. Increased sensitivity of tracheas in immature guinea pigs was observed for both drugs in the absence of aspirin.(ABSTRACT TRUNCATED AT 250 WORDS)

Asunto(s)

Ácido 3-piridinacarboxílico, 1,4-dihidro-2,6-dimetil-5-nitro-4-(2-(trifluorometil)fenil)-, Éster Metílico/farmacología , Agonistas de los Canales de Calcio/farmacología , Músculo Liso/efectos de los fármacos , Piridinas/farmacología , Tráquea/efectos de los fármacos , Animales , Aspirina/farmacología , Antagonismo de Drogas , Femenino , Cobayas , Técnicas In Vitro , Masculino , Contracción Muscular/efectos de los fármacos , Desarrollo de Músculos , Músculo Liso/crecimiento & desarrollo , Músculo Liso/fisiología , Tráquea/crecimiento & desarrollo , Tráquea/fisiología

RESUMEN

Pancuronium is a neuromuscular blocking agent commonly used to eliminate agitation in sick newborn infants requiring mechanical ventilation. Experimental data supporting this method of intervention are controversial, and hemodynamic studies in newborn infants report conflicting results. This study was designed to determine the hemodynamic effects of pancuronium administered under conditions of normoxia, hypoxia, and preexposure to hypoxia in neonatal piglets with normal lungs. After baseline hemodynamic and blood gas measurements were obtained, pancuronium was administered in two i.v. bolus injections of 0.1 mg/kg. Tidal volume and minute ventilation were maintained constant during the experimental procedure by adjusting ventilator settings. Twenty min after pancuronium, no changes from baseline values were found in arterial blood gases, heart rate, cardiac output, mean arterial pressure, systemic vascular resistance, pulmonary artery pressure, pulmonary vascular resistance, central venous pressure, or pulmonary capillary wedge pressure in any of the three conditions studied. In conclusion, pancuronium administered during normoxia, hypoxia, or after preexposure to hypoxia while controlled ventilation is maintained does not alter systemic or pulmonary hemodynamic status of the newborn piglet.

Asunto(s)

Hemodinámica/efectos de los fármacos , Hipoxia/fisiopatología , Pancuronio/farmacología , Animales , Animales Recién Nacidos , Femenino , Masculino , Circulación Pulmonar/efectos de los fármacos , Respiración Artificial , Porcinos

RESUMEN

The purpose of this study was to investigate the ontogeny of guinea pig airway smooth muscle (ASM) responses and the epithelial modulation of these responses. Paired tracheal rings from fetal, newborn, and adult guinea pigs were studied. One of each pair was denuded of airway epithelium (AE) by gentle rubbing. Isometric tension was measured in rings mounted in organ baths filled with Krebs' solution. Cumulative dose-response curves were generated by adding either acetylcholine (ACh) or histamine over a concentration range of 10(-8)-10(-4) M. Significant agent-specific, age-related differences in maximal contraction were seen for both ACh and histamine in intact tissues (Ach: for fetus 66.7 +/- 6.2 x 10(-2) g/mg wet wt, for newborn 51.4 +/- 6.2, for adult 29.3 +/- 2.6; histamine: for fetus 46.1 +/- 5.1, for newborn 72.9 +/- 6.0, for adult 25.3 +/- 3.2). Similar differences in sensitivity to both agents were observed (EC50 with ACh: for fetus 0.80 +/- 0.11 x 10(-6) M; for newborn 0.85 +/- 0.26 x 10(-6) M; for adult 1.7 +/- 0.20 x 10(-6) M; EC50 with histamine; for fetus 1.88 +/- 0.50 x 10(-6) M; for newborn 1.34 +/- 0.16 x 10(-6) M; for adult 3.78 +/- 0.75 x 10(-6) M). Removal of AE caused a significant decrease in maximal responses to ACh in fetal tissue, a smaller, insignificant one for newborn and a nonsignificant alteration for adult tissues. Age-related sensitivity difference was abolished with removal of AE to ACh but not to histamine.(ABSTRACT TRUNCATED AT 250 WORDS)

Asunto(s)

Envejecimiento/fisiología , Hiperreactividad Bronquial/fisiopatología , Músculo Liso/fisiología , Tráquea/fisiología , Acetilcolina/farmacología , Animales , Epitelio/fisiología , Femenino , Cobayas , Histamina/farmacología , Contracción Isométrica/efectos de los fármacos , Contracción Isométrica/fisiología , Masculino , Músculo Liso/efectos de los fármacos

RESUMEN

Furosemide, an inhibitor of Cl-dependent Na+,K+ cotransport, is the most frequently used diuretic in newborns. Recently, furosemide was also demonstrated to decrease bronchial hyper-responsiveness in adults, although little is known about the direct effect of furosemide on smooth muscle of immature animals. This in vitro study was designed to determine the action of furosemide on airway and vascular smooth muscle during ontogeny. Extrathoracic trachea (ET), main stem bronchi, main pulmonary artery, and thoracic aorta ring segments from fetal, newborn, and adult Hartley albino guinea pigs were suspended in HEPES solution for measurement of isometric tension. Furosemide (30 or 300 microM) was administered after preconstriction with an ED35-70 concentration of histamine or acetylcholine for airway and ED40-100 concentration of norepinephrine for vessels. Furosemide (30 microM) caused significant relaxation of airway smooth muscle at all ages. After histamine-induced preconstriction, fetal airway segments exhibited greatest relaxation (183 +/- 28%), with newborn airway demonstrating 123 +/- 15% relaxation and modest relaxation seen in adults (40 +/- 4%). This pattern was similar for both ET and bronchus and appeared greater for histamine compared with ACh preconstriction. Epithelial removal slightly enhanced relaxation. Furosemide also relaxed pulmonary artery segments, but at a 10-fold higher concentration. In striking contrast to the pattern seen in airway, adult pulmonary artery relaxed more than newborn and newborn, more than fetus. Cyclooxygenase blockade and endothelium removal did not change pulmonary artery relaxation. Furosemide did not significantly relax aorta after NE preconstriction. Taken together, these results suggest that furosemide may be more effective in relaxing airway compared with vascular smooth muscle, and the ontogeny of these responses indicates a greater efficacy and selectivity in airways of immature animals.

Asunto(s)

Aorta Torácica/efectos de los fármacos , Bronquios/efectos de los fármacos , Furosemida/farmacología , Músculo Liso Vascular/efectos de los fármacos , Músculo Liso/efectos de los fármacos , Arteria Pulmonar/efectos de los fármacos , Tráquea/efectos de los fármacos , Acetilcolina/farmacología , Factores de Edad , Animales , Animales Recién Nacidos , Aorta Torácica/embriología , Bronquios/embriología , Relación Dosis-Respuesta a Droga , Evaluación Preclínica de Medicamentos , Femenino , Feto/efectos de los fármacos , Furosemida/administración & dosificación , Cobayas , Histamina/farmacología , Técnicas In Vitro , Masculino , Músculo Liso/embriología , Músculo Liso Vascular/embriología , Norepinefrina/farmacología , Embarazo , Arteria Pulmonar/embriología , Factores de Tiempo , Tráquea/embriología

RESUMEN

Significant adverse perinatal effects of maternal methamphetamine use have been reported, but little is known about factors influencing methamphetamine screening test results during the perinatal period. We tested the hypothesis that gestational age would affect quantitative recovery of methamphetamine in meconium and amniotic fluid. Time-bred guinea pigs received an intraperitoneal (i.p.) injection of 1 mg/kg methamphetamine at either 44 days (0.65 of term, n = 5), 50 days (0.74, n = 8), 56 days (0.82, n = 9) or 63 days (0.93, n = 4) gestation. At 1 or 7 days after i.p. methamphetamine, meconium and amniotic fluid were collected for quantitative methamphetamine assay by gas chromatography-mass spectrometry. Recovery from amniotic fluid and meconium 1 day after injection was influenced by gestational age. Greater values in amniotic fluid and meconium and a higher percentage of positive samples were seen in older fetuses. Collectively at all gestational ages, combined testing of amniotic fluid and meconium yielded detectable methamphetamine or its metabolites in 87% of guinea pigs 1 day after injection. However, methamphetamine was not detectable 1 week after injection in any sample (n = 63) at either 0.74 or 0.82 of term except for one positive amniotic fluid sample. Finally, demethylation of methamphetamine to amphetamine was higher in older fetuses.(ABSTRACT TRUNCATED AT 250 WORDS)

Asunto(s)

Líquido Amniótico/química , Meconio/química , Metanfetamina/análisis , Animales , Femenino , Edad Gestacional , Cobayas , Metanfetamina/metabolismo , Embarazo

RESUMEN

Linear vasopressin analogs lacking a cyclic hexapeptide ring have recently been reported to possess vasopressin antagonist activity. In conscious, chronically catheterized, euhydrated Sprague-Dawley rats, we have compared the effects of two noncyclic vasopressin analogs, peptide 1 ([1-admantaneacetic acid,2-(O-ethyl)-D-tyr,4-val,6-(2-aminobutyric acid),9-arg]arginine vasopressin) and peptide 2 ([1-propionic acid, 2-(O-ethyl)-D-tyr,4-val,6-(2-aminobutyric acid),9- arg]arginine vasopressin), with a cyclic arginine vasopressin antagonist (SK&F 105494; [1-des cysteine, cyclo(2-O-ethyl-D-tyrosine,6-L-(2-amino-6,6-cyclopentamethylene suberic acid], 4-valine,7-arginine,8-D-arginine, 9-des glycine]-vasopressin). All three analogs caused a dose-dependent increase in urine flow by increasing free-water clearance without significantly changing osmotic clearance or sodium excretion, indicating true functional vasopressin antagonism. Peptides 1 and 2 were as efficacious in inducing a diuresis as SK&F 105494. The order of diuretic potency among the three analogs in vivo was the same as the order of potency determined by in vitro binding to rat renal membrane homogenates, suggesting that the analogs exerted their diuretic effect by acting at renal vasopressin receptors. Thus, noncyclic vasopressin analogs, which are easier to synthesize then cyclic structures, could provide new strategies in the design of drugs for the treatment of water balance disorders.

Asunto(s)

Arginina Vasopresina/análogos & derivados , Diuréticos/farmacología , Animales , Arginina Vasopresina/antagonistas & inhibidores , Arginina Vasopresina/farmacología , Presión Sanguínea/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Masculino , Ratas , Ratas Endogámicas

RESUMEN

We have demonstrated that arginine vasopressin (AVP) is degraded to desglycinamide AVP by a trypsinlike enzyme found in guinea pig amniotic fluid. Incubation of [3H]AVP with guinea pig amniotic fluid in vivo or in vitro produced a metabolite that comigrated on high-pressure liquid chromatography with desglycinamide AVP in three different buffer systems. Also, AVP antisera that cross-reacted with standard desglycinamide AVP could detect this amniotic fluid metabolite. Because the enzyme responsible for the cleavage of glycinamide from AVP was likely to be trypsin, experiments with aprotinin, a trypsin inhibitor, were conducted. Results demonstrated that the production of the amniotic fluid AVP metabolite could be completely blocked in the presence of the trypsin inhibitor. In addition, examination of amniotic fluid collected from fetuses in the second half of gestation (term = 68 days) showed that AVP could not be metabolized to desglycinamide AVP until after 52 days of gestation. In conclusion, AVP appears to be metabolized by a trypsinlike enzyme in amniotic fluid, and because trypsin is a general proteolytic enzyme, the amniotic compartment may also serve as a clearance site for other proteins.

Asunto(s)

Líquido Amniótico/enzimología , Tripsina/fisiología , Vasopresinas/metabolismo , Líquido Amniótico/análisis , Animales , Cromatografía Líquida de Alta Presión , Femenino , Cobayas , Sueros Inmunes/inmunología , Factores de Tiempo , Tripsina/metabolismo , Vasopresinas/inmunología