Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.11.18 (MAP)
 7,412 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Twelve neonates with severe lung disease were studied while mechanically ventilated with volume pre-set infant ventilators, using different I:E ratios and different airway pressure waves. While FIO2 tidal volume, respiratory rate, and PEEP remained constant, I:E ratios were increased, first by reducing inspiratory flow rate, which produced a triangular pressure wave, and then by using an inspiratory time hold mechanism, which produced an inspiratory plateau or squared pressure wave. Peak inspiratory pressure, mean airway pressure, PaO2, PaCO2, pH, and blood pressure were measured and compared for each I:E ratio and pressure wave combination. In all patients, increases in oxygenation appeared to be directly related to increases in MAP. Optimum oxygenation and ventilation occurred with the I:E ratio and pressure wave combination that produced the highest MAP. Because MAP changes with any alteration in PEEP, I:E ratio, or airway pressure wave, it is a clinically useful composite measure of all pressures transmitted to the airways by a mechanical ventilator.
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PMID:Variations in inspiratory:expiratory ratio and airway pressure wave form during mechanical ventilation: the significance of mean airway pressure. 75 87

Bronchopulmonary dysplasia is a chronic, sometimes fatal lung disease, which primarily affects premature infants and often leads to a dependence on mechanical ventilation lasting many months. To identify prognostic factors of mortality at 1 and 2 months of age, the authors reviewed the medical records of the 144 neonates admitted to two neonatal intensive care units in Seattle from January 1, 1986, through December 31, 1988, who required mechanical ventilation throughout the first month of life. Likely predictors of mortality were tested by logistic regression analysis. The calculated mean airway pressure at 30 days of age (MAP30) and the diagnosis of bacterial sepsis at any time during the first month of life (Bact 0-30) were statistically significant predictors of mortality (P less than .001 and P = .018, respectively) and had the lowest deviance in the regression model. The probability of mortality was estimated by 1/(1 + e-chi), where chi = -6.510 + 0.4588 (MAP30) + 1.475 (Bact 0-30), and where MAP30 is expressed as centimeters of water pressure (1 cm H2O = 0.0978 kPa) and the presence or absence of bacteremia is 1 and 0, respectively. The records of the 57 infants who still required mechanical ventilation at 60 days of age were reanalyzed with clinical data available during the first 2 months of life. Mean airway pressure (MAP 60) and the fraction of inspired oxygen (F60) at 60 days of age combined to form the best predictors of mortality, where chi = 7.668 + 0.2940 (MAP 60) + 5.935 (F60).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Estimation of mortality risk in chronically ventilated infants with bronchopulmonary dysplasia. 195 31

Vasodilators have demonstrated efficacy in neonates with depressed myocardial function. The magnitude of benefit depends on the preexisting hemodynamic state and concurrent treatment modalities. In patients with increased filling pressures, vasodilators increase cardiac output with negligible effect on MAP, with volume resuscitation to restore pretreatment filling pressures offering additional benefit. The rationale for use in neonatal respiratory disease remains less clear, with no vasoactive drug showing selective pulmonary vasodilatation. Benefit no doubt accrues from the improved coronary perfusion that occurs with reduction in filling pressures. In addition, reduced interventricular diastolic dependence and thereby improved ventricular compliance, as well as the afterload-reducing effect of decreased chamber size, may significantly reduce the effect of the lung disease on myocardial functioning.
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PMID:The use of inotropic and afterload-reducing agents in neonates. 306 49

Ten neonates with severe lung disease were studied while mechanically ventilated with standard volume preset infant ventilators, using two different ventilatory patterns. Slow ventilatory rates and high tidal volumes were alternated with rapid rates and low tidal volumes; minute ventilation, FIo2, PEEP, and I:E ratios were held constant. Peak inspiratory pressure, mean airway pressure, expiratory time, Pao2, Paco2, pH, and arterial blood pressure were measured and compared for each frequency-tidal volume combination. The best arterial oxygenation occurred at the combination of settings that produced the highest mean airway pressure and always during low frequency-high tidal volume ventilation (P less than 0.001). Changes in oxygenation appeared to be directly related to changes in MAP. A second experiment examined two different ventilator systems' responses to changes in ventilatory rate. When the rate of one ventilator (Bourns LS104 volume preset) was increased, MAP increased. When the rate of the other ventilator (Bennett PR2 pressure preset) increased, MAP decreased. These observations suggest that there is a direct relationship between MAP and orterial oxygenation, and that the supposed advantages of one ventilatory pattern over the other may be secondary to inadvertent changes in subtle pressure-time relationships within the respiratory cycle and incidental changes in MAP. These changes may vary from one ventilator to another.
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PMID:A comparison of the effects of high frequency--low tidal volume and low frequency--high tidal volume mechanical ventilation. 738 29

There is a continuing need for development of new treatments for lung disease. Basic scientific investigations are identifying novel targets for the development of new approaches to therapy of a range of respiratory conditions. Coupled with the advances in technology being harnessed by the pharmaceutical and biotechnological industries, there is now an impressive range of potential treatments including gene therapy, not just for cystic fibrosis but also for a range of inflammatory lung conditions, anti-cytokine and anti-adhesion molecule approaches, and targeting of intracellular signal transduction pathways including cyclic AMP metabolism, tyrosine kinases and MAP kinases. "Old" molecules such as heparin and secretory leukoprotease inhibitor (SLPI) are demonstrating new beneficial activities. Simple molecules such as nitric oxide (NO) gas may be involved in the pathophysiology of different airway conditions. It is an exciting time for respiratory science and a time for optimism for those seeking new approaches to the treatment of lung diseases.
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PMID:New ideas on the pathophysiology and treatment of lung disease. 965 57

The time course of intensive care for severe respiratory syncytial virus (RSV) lower respiratory tract illness may be predicted by the severity of gas exchange during the first 48 h of mechanical ventilation. To test this hypothesis, two studies were undertaken in RSV-positive mechanically ventilated patients who did not have chronic lung disease, congenital heart disease or immunodeficiency. First, a retrospective criteria-generating review of 45 infants was carried out. In these infants, more severe lower airway disease, as demonstrated by four-quadrant consolidation on chest X-ray, was associated with 'best' alveolar arterial oxygen gradients (AaDO2, torr) and mean airway pressure (MAP, cm H2O) values as follows: first 24h, AaDO2 > 400 and MAP > 10 (positive and negative predictive values 100% and 97%, respectively); second 24 h, AaDO2 > or = 300 and MAP > 10 (positive and negative predictive values 91% and 100%, respectively). The second study, a prospective, hypothesis-testing, analysis of length-of-stay in 44 infants stratified according to the above AaDO2 and MAP criteria demonstrated that the duration of intensive care was longer in the severe group: median (interquartile range in days) 17 (15-39) vs 7 (4-8) (p < 0.01). We suggest that, in mechanically ventilated infants with RSV, the time course of intensive care is predictable based on early clinical features and respiratory parameters. Therefore reports on the effectiveness of special therapies using intensive care stay as a measure of outcome should be interpreted with respect to these observations before drawing conclusions about efficacy.
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PMID:Time course of severe respiratory syncytial virus infection in mechanically ventilated infants. 1097 23

Changes in the osmolarity of the airway surface fluid have been described to be involved in the pathogenesis of exercise induced asthma, and are suggested as the major cause of the lung disease in cystic fibrosis. In this study, we examined the signaling pathway of hyperosmotic challenge to interleukin-8 (IL-8). Hyperosmolarity (NaCl) caused a time- and concentration-dependent increase in IL-8 expression and secretion in bronchial epithelial cells. These effects could be blocked by antioxidants, such as DMSO, DMTU, DTT, and beta-mercaptoethanol, suggesting an involvement of reactive oxygen intermediates (ROI) in the signal transduction of hyperosmolarity-induced IL-8 synthesis. Since IL-8 is regulated by MAP kinases, we examined the influence of MAP kinase inhibitors on hyperosmolarity-induced IL-8 expression. The results show that this induction is regulated by p38 MAPK and not by ERK1/2. Furthermore, antioxidants blocked the activation of p38 MAPK induced by hyperosmolarity. These results suggest that ROIs are critical for p38 MAPK mediated IL-8 expression by hyperosmolarity.
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PMID:Reactive oxygen intermediates are involved in IL-8 production induced by hyperosmotic stress in human bronchial epithelial cells. 1102 15

High-dose ibuprofen therapy has demonstrated to slow deterioration in pulmonary function in children with cystic fibrosis with mild lung disease. Therapeutic drug monitoring has been recommended to maintain peak concentrations within the range of 50 to 100 mg/L to ensure efficacy. Current methods for dosage individualization are based on dose proportionality using visual inspection of the peak concentration; however, because of interpatient variability in the absorption of the various formulations this method may result in incorrect assessments of the peak concentration achieved. Maximum a posteriori Bayesian analysis (MAP-B) has proven to be a useful and precise method of individualizing the dose of aminoglycosides but requires a description of the structural model. In this study we performed parametric population modeling analysis on plasma concentrations of ibuprofen after single doses of 20 to 30-mg/kg tablet or suspension in children with cystic fibrosis. Patients evaluated in this study were part of a single dose pharmacokinetic study that has been published previously. A one-compartment model with first order absorption and a lag time best described the data. The pharmacokinetic parameters differed significantly depending on the formulation administered. D-optimal sampling times for the suspension and tablet formulations are 0, 0.25 to 0.5, 1, and 3 to 4 hours and 0, 0.25 to 0.5, 1 to 1.5, and 5 hours respectively. Use of MAP-B analysis performed with the 4 d-optimal sampling strategy resulted in accurate and precise estimates of the pharmacokinetic parameters when compared with maximum likelihood analysis using the complete plasma concentrations data set. Further studies are needed to evaluate the performance of these models and the impact on patient outcomes.
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PMID:Development of population pharmacokinetic models and optimal sampling times for ibuprofen tablet and suspension formulations in children with cystic fibrosis. 1189 78

Steroids administrated antenatally to the mothers improve postnatal outcomes of the newborns with pleiotropic effects. Furthermore steroids have been used in preterm infants to prevent or treat chronic lung disease. Synthetical glucocorticoids readily cross placental barrier and reach significant pharmacologic levels in the fetus: besides their well known pulmonary effects they have a concomitant maturational effect of postnatal renal function in preterm infants both with a direct and indirect effect. Endogenous and exogenous glucocorticoids play a role in the maintenance of glomerular filtration (GFR). The antenatal administration of steroids increases the GFR, in association to the maturation of the tubular function. According to different studies the improvement of renal function, expressed by the increase of GFR, is only partially referable to the increase of MAP and the improvement of the cardiovascular status, while it was imputable to a direct renal effect of the steroids, especially on the renal blood flow, on functional glomerular surface area available for filtration and on the glomerular filtrate of the single cortical nephron. However debate remains about the mechanism through which steroids would act on the renal vascular smooth muscolature. The increase the GFR observed after the antenatal administration of glucocorticoids in premature fetuses is also accompanied by an increase of urinary flow and of fractional excretion of sodium. Glucocorticoids would increase the proximal reabsorption of sodium increasing directly the function and the expression of the sodium transporters and both indirectly and directly increasing the activity of Na-K-ATPase. In extremely low weight antenatal administration of betamethasone or dexamethasone was associated with lower estimated insensible water loss, secondary to a direct maturational effect in the skin epithelial barrier, as well as an increased reabsorption of the fetal lung fluid. Moreover antenatal glucocorticoid administration was associated, at birth, to a significant suppression of plasma renin activity and angiotensin II in comparison to the controls. Despite the wide use of the steroidal therapy in the prevention of the bronchopulmonary dysplasia, only few articles, in literature, analyse the effects of glucocorticoids on postnatal renal function, such as the increase in urinary flow. The authors think that steroids contribute in a meaningful way to the clinical improvement observed in children with BPD through the maturative action on the premature kidney with effect both at glomerular and tubular level.
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PMID:Renal effects of antenatally or postnatally administered steroids. 1198 24

Because echocardiographic studies on infants with chronic lung disease (CLD) suggest that pulmonary hypertension (PH) may contribute to its severity, we studied acinar arterial walls in the following surfactant-era infants: controls (n=38): 22-41 weeks of gestational age (GA), exposed briefly to oxygen and positive pressure ventilation, died within 48 hr of birth; prolonged rupture of fetal membranes (PROM) and persistent pulmonary hypertension (PPHN) (n=17); and SCORE (integrated area under curve of average daily FiO2 x average daily MAP) groups (<20, 20-69, and 70-500; mild, moderate, and severe clinical lung disease, respectively, n=35): 23-30 weeks GA, lived 7-79 days. Lungs were stained for elastic tissue and smooth muscle actin. Vessels were assessed for percent of vessel circumference with smooth muscle, extent of elastic laminae in the walls, and percent arterial wall thickness (%AWT) at three levels: terminal to respiratory bronchiole transition (TRB), alveolar duct, and saccule. At the alveolar ductal and saccular levels, percent arterial wall thickness (%AWT) in mild CLD (SCORE < 20) was less than controls (P < 0.05) and those with more severe CLD (SCORE 70-500), indicating that normal postnatal arterial wall thinning may be delayed, or there is remodeling associated with increased %AWT. Severe CLD infants also had a significantly higher percent of circumferential actin than those with milder disease (SCORE < or = 69) and controls. In moderate and severe CLD, there was an increase in extent of the elastic laminae compared to controls and mild CLD. These changes were also significantly greater in PROM and PPHN infants compared to even severe CLD. We conclude that PH is a real possibility in severe CLD infants after discharge at 36 weeks. Grading the severity of CLD at discharge, and echocardiographic studies, may guide subsequent oxygen therapy.
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PMID:Acinar arterial changes with chronic lung disease of prematurity in the surfactant era. 1461 39


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