Biomedical subjects

Pilar Fernández-Segoviano

Publications and source records attributed to Pilar Fernández-Segoviano.

8 recordsLinked to original sources

PubMed2006

Ventilation-induced lung injury in rats is associated with organ injury and systemic inflammation that is attenuated by dexamethasone.

OBJECTIVE: To determine whether mechanical ventilation using high tidal volume is associated with nonpulmonary organ dysfunction that can be attenuated by dexamethasone. DESIGN: Prospective randomized animal intervention study. SETTING: Animal care facility in a university hospital. SUBJECTS: Sedated and tracheostomized male Sprague-Dawley rats. INTERVENTIONS: Three groups of rats were ventilated with different strategies: tidal volume = 9 mL/kg, positive end-expiratory pressure = 8 cm H(2)O, control group (C); tidal volume = 35 mL/kg, positive end-expiratory pressure = 0 cm H(2)O, overventilated group (OV); and tidal volume = 35 mL/kg, positive end-expiratory pressure = 0 cm H(2)O, plus administration of 6 mg/kg dexamethasone intraperitoneally (OV + dexamethasone). All rats were ventilated for 75 mins with respiratory rate = 70 breaths/min, FIO(2) = 0.35, and plateau time = 0. MEASUREMENTS AND MAIN RESULTS: Mean arterial pressure and peak airway pressure were monitored. We measured arterial blood gases, aspartate aminotransferase, alanine aminotransferase, lactate, nitrates and nitrites, tumor necrosis factor-alpha, and interleukin-6 serum concentration. Lung slices were prepared for blind histologic examination. Heart tissue was analyzed for cyclooxygenase-1 and -2 expression (reverse transcription-polymerase chain reaction). Compared with the C group, the OV group showed hypotension; worsened gas exchange; increased aspartate aminotransferase, lactate, nitrates and nitrites, and interleukin-6 serum concentrations; and hyaline membrane formation in the lungs, as well as increased cyclooxygenase-1 and cyclooxygenase-2 expression in the heart. Dexamethasone prevented the pulmonary and cardiovascular injury and attenuated the increase in aspartate aminotransferase, nitrates and nitrites, interleukin-6, and cyclooxygenase-1 and cyclooxygenase-2 expression. CONCLUSIONS: High tidal volume ventilation induces cardiovascular, pulmonary, and liver injury as well as a systemic proinflammatory response. These changes are attenuated by dexamethasone, suggesting that inflammatory rather than purely hemodynamic mechanisms are involved in the changes induced by high tidal volume ventilation.

Animals↗

PubMed2006

Contributions of vascular flow and pulmonary capillary pressure to ventilator-induced lung injury.

OBJECTIVE: To evaluate the influence of vascular flow on ventilator-induced lung injury independent of vascular pressures. DESIGN: Laboratory study. SETTING: Hospital laboratory. SUBJECTS: Thirty-two New Zealand White rabbits. INTERVENTIONS: Thirty-two isolated perfused rabbit lungs were allocated into four groups: low flow/low pulmonary capillary pressure; high flow/high pulmonary capillary pressure; low flow/high pulmonary capillary pressure, and high flow/low pulmonary capillary pressure. All lungs were ventilated with peak airway pressure 30 cm H2O and positive end-expiratory pressure 5 cm H2O for 30 mins. MEASUREMENTS AND MAIN RESULTS: Outcome measures included frequency of gross structural failure (pulmonary rupture), pulmonary hemorrhage, edema formation, changes in lung compliance, pulmonary vascular resistance, and pulmonary ultrafiltration coefficient. Lungs exposed to high pulmonary vascular flow ruptured more frequently, displayed more hemorrhage, developed more edema, suffered larger decreases in compliance, and had larger increases in vascular resistance than lungs exposed to low vascular flows (p < .05 for each pairwise comparison between groups). CONCLUSIONS: These findings suggest that high pulmonary vascular flows might exacerbate ventilator-induced lung injury independent of their effects on pulmonary vascular pressures.

Animals↗

PubMed2005

Massive brain injury enhances lung damage in an isolated lung model of ventilator-induced lung injury.

OBJECTIVE: To assess the influence of massive brain injury on pulmonary susceptibility to injury attending subsequent mechanical or ischemia/reperfusion stress. DESIGN: Prospective experimental study. SETTING: Animal research laboratory. SUBJECTS: Twenty-four anesthetized New Zealand White rabbits randomized to control (n = 12) or induced brain injury (n = 12) group. INTERVENTIONS: After randomization, brain injury was induced by inflation of an intracranial balloon-tipped catheter, and animals were ventilated with a tidal volume of 10 mL/kg and zero end-expiratory pressure for 120 mins. Following heart-lung block extraction, isolated and perfused lungs were subjected to injurious ventilation with peak airway pressure 30 cm H2O and positive end-expiratory pressure 5 cm H2O for 30 mins. MEASUREMENTS AND MAIN RESULTS: No difference was observed between groups in gas exchange, lung mechanics, or hemodynamics during the 2-hr in vivo period following induction of brain injury. However, after 30 mins of ex vivo injurious mechanical ventilation, lungs from the brain injury group showed greater change in ultrafiltration coefficient, weight gain, and alveolar hemorrhage (all p < .05). CONCLUSIONS: Massive brain injury might increase lung vulnerability to subsequent injurious mechanical or ischemia-reperfusion insults, thereby increasing the risk of clinical posttransplant graft failure.

Animals↗

PubMed2005

Acute respiratory distress syndrome: underrecognition by clinicians and diagnostic accuracy of three clinical definitions.

OBJECTIVE: To determine and compare the diagnostic accuracy of three clinical definitions of acute respiratory distress syndrome (ARDS): (1) the American-European consensus conference definition; (2) the lung injury score; and (3) a recently developed Delphi definition. A second objective was to determine the accuracy of clinical diagnoses of ARDS made in daily practice. DESIGN: Independent comparison of autopsy findings with the daily status of clinical definitions, constructed with data abstracted retrospectively from medical records. SETTING: Tertiary intensive care unit. PATIENTS: One hundred thirty-eight patients from the period 1995 through 2001 who were autopsied after being mechanically ventilated. INTERVENTIONS: Clinical ARDS diagnoses were determined daily without knowledge of autopsy results. Charts were reviewed for any mention of ARDS in the clinical notes. Autopsies were reviewed independently by two pathologists for the presence of diffuse alveolar damage. The sensitivity and specificity of the definitions were determined with use of diffuse alveolar damage at autopsy as the reference standard. MEASUREMENTS AND MAIN RESULTS: Diffuse alveolar damage at autopsy was documented in 42 of 138 cases (30.4%). Only 20 of these 42 patients (47.6%) had any mention of ARDS in their chart. Sensitivities and specificities (95% confidence intervals) were as follows: American-European definition, 0.83 (0.72-0.95), 0.51 (0.41-0.61); lung injury score, 0.74 (0.61-0.87), 0.77 (0.69-0.86); and Delphi definition, 0.69 (0.55-0.83), 0.82 (0.75-0.90). Specificity was significantly higher for both the lung injury score and Delphi definition than for the American-European definition (p < .001 for both), whereas comparisons of sensitivity, which was higher for the American-European definition, were not significantly different (p = .34 and p = .07, respectively). CONCLUSIONS: Acute respiratory distress syndrome appears underrecognized by clinicians in patients who die with this syndrome. In this population, the specificities of existing clinical definitions vary considerably, which may be problematic for clinical trials.

Aged↗

PubMed2005

Large tidal volume mechanical ventilation induces vascular dysfunction in rats.

BACKGROUND: Experimental studies have shown that mechanical ventilation using high tidal volumes (V(T)) damages the lungs, causing pulmonary edema. We tested the hypothesis that high V(T) ventilation in rats induces major vascular dysfunction. METHODS: Healthy Sprague-Dawley rats, weighing (mean +/- SD) 340 +/- 15 g, were ventilated with either V(T) = 9 mL/kg and positive end-expiratory pressure (PEEP) = 8 (n = 8) or V(T) = 35 mL/kg and PEEP = 0 (n = 8). The high V(T) used in the injurious ventilation group is in the V(T) range used in other studies to induce lung damage in a short period of time in rats. Lungs were removed for examination under light microscopy and vascular rings from the thoracic aorta were studied for isometric tension recording. RESULTS: Relaxations to acetylcholine (p < 0.001) and sodium nitroprusside (p < 0.05) and contractions to norepinephrine were markedly decreased (p < 0.001) in the high V(T) group, as compared with the low V(T) group. CONCLUSION: Injurious mechanical ventilation in normal rats is associated with vascular dysfunction characterized by decreased relaxation to an endothelium-dependent vasodilator and to a nitrous oxide donor and by decreased response to norepinephrine.

Analysis of Variance↗

PubMed2004

Comparison of clinical criteria for the acute respiratory distress syndrome with autopsy findings.

BACKGROUND: The American-European Consensus Conference definition for the acute respiratory distress syndrome (ARDS) has never been validated. OBJECTIVE: To compare clinical criteria for ARDS with autopsy findings. DESIGN: Independent comparison of autopsy findings with clinical characteristics retrospectively abstracted from medical records. SETTING: Tertiary medical-surgical intensive care unit. PARTICIPANTS: 382 patients who underwent clinical autopsy. MEASUREMENTS: Sensitivity, specificity, and likelihood ratios for clinical criteria were calculated in 3 cohorts by using diffuse alveolar damage at autopsy as the reference standard. The 3 cohorts were 1) all patients, 2) patients with any risk factor for ARDS, and 3) patients who were separated according to their pulmonary or extrapulmonary risk factors. RESULTS: 127 patients (33%) met the clinical criteria, and 112 (29%) had diffuse alveolar damage. In all patients, the sensitivity of the clinical definition was 75% (95% CI, 66% to 82%) and the specificity was 84% (CI, 79% to 88%). In 284 patients with risk factors, the sensitivity was 76% (CI, 67% to 83%) and the specificity was 75% (CI, 68% to 81%). Compared with patients with pulmonary risk factors, patients with extrapulmonary risk factors had significantly higher sensitivity (61% vs. 85%; P = 0.009) and the specificity did not statistically significantly differ (69% vs. 78%; P > 0.2). LIMITATIONS: Only patients who died and underwent autopsy could be included in this study, so these results may not apply to less severe cases of ARDS. CONCLUSIONS: In a series of autopsy patients, the accuracy of the American-European Consensus Conference definition of ARDS was only moderate. The definition was more accurate for patients with extrapulmonary risk factors than for patients with pulmonary risk factors.

Aged↗

PubMed2002

Interaction between hemoglobin and glutathione in the regulation of blood flow in normal and septic pigs.

BACKGROUND: Hemoglobin (Hb) induces vasoconstriction by heme group binding nitric oxide in an irreversible fashion. Recent in vitro studies indicate that the thiol groups in Hb reversibly bind nitric oxide and participate in trans-nitrosylation reactions with other thiols. Sepsis is a pathophysiologic state characterized by vasodilation mediated, at least in part, by an excessive release of nitric oxide. The role of nitrosothiols (RSNOs) in these changes is unknown. OBJECTIVES: We tested the following in a porcine model of sepsis: (i) whether glutathione (GSH) reverses the hemodynamic effects of Hb; (ii) whether GSH induces an increase in blood flow in sepsis; (iii) whether RSNO plasma concentration increases in sepsis and is related to hypotension. DESIGN: Nonrandomized animal controlled study. SETTING: Animal research facility in a university hospital. SUBJECTS: Anesthetized pigs were monitored with a pulmonary artery catheter and ultrasonic blood flow probes in the mesenteric artery and the portal vein for measurement of systemic, mesenteric, and portal blood flows (Q(TOT), Q(MES), and Q(POR), respectively). Four groups of pigs were studied: nonseptic, septic, nonseptic treated with Hb (stroma-free purified porcine hemoglobin), and septic treated with Hb (n = 6 in each group). INTERVENTIONS: Sepsis was induced at 0 min by the administration of live Escherichia coli. Hb (400 mg/kg/hr) was administered at 240 mins, followed by glutathione (1 g iv). MEASUREMENTS AND MAIN RESULTS: Hb induced a pressor response and a decrease in Q(TOT), Q(MES), and Q(POR). Glutathione reversed the effects of Hb on Q(MES) and Q(POR). In septic pigs not treated with Hb, GSH induced an increase in Q(POR). RSNO plasma concentration increased after the induction of sepsis and correlated significantly with blood pressure. CONCLUSIONS: These results indicate the reversibility of the effects of Hb by GSH, probably by interactions between nitric oxide and the reduced sulfhydryl groups in Hb, and suggest a role of RSNOs in the cardiovascular changes of sepsis.

Analysis of Variance↗

PubMed2002

Classification of renal proteinuria: a simple algorithm.

Total protein, albumin, alpha1-microglobulin, and immunoglobulin G (IgG) were analyzed in 1,622 urine samples without Bence-Jones proteinuria or gross hematuria. There was correlation with the histological picture obtained on renal biopsy in 61 patients. We established 24-h reference intervals for alpha1-microglobulin and IgG on 659 urine samples with total protein and albumin excretion rates below 100 mg/24 h and 30 mg/24 h, respectively, and creatinine clearance above 80 ml/min. The central 95% reference interval was found to be between 4 and 17 mg/24 h for alpha1-microglobulin and between 3 and 8.5 mg/24 h for IgG. In 80 urine samples with albumin excretion rate above 30 mg/24 h and alpha1-microglobulin and IgG within their reference intervals, we analyzed the 95% central interval of the distribution of the IgG/albumin ratios, and it was found to be within 0.01 and 0.20 (0.90 confidence interval: 0.17-0.24). Proteinuria was considered to be of the selective glomerular type if the albumin excretion rate was abnormal and the IgG/albumin ratio was under 0.20, even when the IgG excretion was within a pathological range. For the classification of proteinuria as predominantly tubular, we estimated the alpha1-microglobulin/albumin ratio in 173 urine samples with normal excretion rates of albumin and IgG and pathological excretion of alpha1-microglobulin. The discriminating value of 0.91 (0.90 confidence interval: 0.78-1.08) was accepted in order to define proteinuria of a tubular origin in the presence of a pathological albumin excretion rate. The association between albumin and IgG excretion rates and tubular reabsorption of the alpha1-microglobulin normally filtered by the glomerulus was studied in 33 urine samples from patients with no histologically significant tubulo-interstitial or vascular disease and a serum creatinine concentration below 141 pmol/l. The optimal curve-fitting function between albumin plus IgG and alpha1-microglobulin excretion rates was of the quadratic type (r = 0.927). Mixed proteinuria was considered when both, albumin and alpha1-microglobulin excretion rates were pathological and could not be included in the previously described groups.

Algorithms↗