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Biomedical subjects

P V Romero

Publications and source records attributed to P V Romero.

At least 19 recordsLinked to original sources

Understanding the mechanisms of lung mechanical stress.

Physical forces affect both the function and phenotype of cells in the lung. Bronchial, alveolar, and other parenchymal cells, as well as fibroblasts and macrophages, are normally subjected to a variety of passive and active mechanical forces associated with lung inflation and vascular perfusion as a result of the dynamic nature of lung function. These forces include changes in stress (force per unit area) or strain (any forced change in length in relation to the initial length) and shear stress (the stress component parallel to a given surface). The responses of cells to mechanical forces are the result of the cell's ability to sense and transduce these stimuli into intracellular signaling pathways able to communicate the information to its interior. This review will focus on the modulation of intracellular pathways by lung mechanical forces and the intercellular signaling. A better understanding of the mechanisms by which lung cells transduce physical forces into biochemical and biological signals is of key importance for identifying targets for the treatment and prevention of physical force-related disorders.

Extracellular Matrix↗

[Analysis of oxidative stress in exhaled breath condensate from patients with severe pulmonary infections].

OBJECTIVE: Oxidative stress is an intrinsic part of the chain of events leading to inflammation of the airways caused by bacterial infection. The aim of this study was to determine whether analysis of exhaled breath condensate from patients with severe lung infections reveals changes in the redox state at the airway surface. PATIENTS AND METHODS: The study included a total of 48 subjects divided into 4 groups: individuals without respiratory disease (n=14), patients with multilobar pneumonia (n=13), patients who had chronic obstructive pulmonary disease with superinfection (n=14), and mechanically ventilated patients with severe pneumonia (n=7). A sample of exhaled breath condensate was obtained within the first 72 hours of hospital admission and the concentrations of nitrite, nitrate, 8-isoprostane, and myeloperoxidase (MPO) were determined. RESULTS: Significant differences in the concentrations of nitrite, 8-isoprostane, and MPO were observed between patients and individuals without respiratory disease but no differences were found between the 3 patient groups. The concentration of MPO was correlated with the concentrations of 8-isoprostane and nitrate, which were normalized to the nitrite concentration. CONCLUSIONS: Analysis of the concentrations of 8-isoprostane and MPO in exhaled breath condensate allows assessment of oxidative stress in the airways of patients with severe lung infections.

Adult↗

Volumetric capnography in the mechanically ventilated patient.

Expiratory capnogram provides qualitative information on the waveform patterns associated with mechanical ventilation and quantitative estimation of expired CO2. Volumetric capnography simultaneously measures expired CO2 and tidal volume and allows identification of CO2 from 3 sequential lung compartments: apparatus and anatomic dead space, from progressive emptying of alveoli and alveolar gas. Lung heterogeneity creates regional differences in CO2 concentration and sequential emptying contributes to the rise of the alveolar plateau and to the steeper the expired CO2 slope. The concept of dead space accounts for those lung areas that are ventilated but not perfused. In patients with sudden pulmonary vascular occlusion due to pulmonary embolism, the resultant high V/Q mismatch produces an increase in alveolar dead space. Calculations derived from volumetric capnography are useful to suspect pulmonary embolism at the bedside. Alveolar dead space is large in acute lung injury and when the effect of positive end-expiratory pressure (PEEP) is to recruit collapsed lung units resulting in an improvement of oxygenation, alveolar dead space may decrease, whereas PEEP-induced overdistension tends to increase alveolar dead space. Finally, measurement of physiologic dead space and alveolar ejection volume at admission or the trend during the first 48 hours of mechanical ventilation might provide useful information on outcome of critically ill patients with acute lung injury or acute respiratory distress syndrome.

Capnography↗

Coherence between oxygen saturation and heart rate obtained from pulse oximetric recordings in obstructive sleep apnoea.

In obstructive sleep apnoea (OSA) cyclical changes in oxygen saturation and heart rate in the period range of 30-120 s are observed. In these patients, we prospectively analyse the coherence of nocturnal SaO(2) and heart rate signals. A sample of 201 clinically suspected of having OSA were studied using nocturnal pulse oximetric and complete polysomnography. Coherence function versus period curves were categorized into three patterns: a positive pattern showing a predominant positive peak value of coherence in the period range of 30-120 s; a negative pattern if the predominant coherence was negative in the same range; and an undetermined pattern if no predominance was detected. One hundred and thirteen patients present a positive coherence pattern; 74.3% of these have OSA. A negative coherence pattern was observed for 28 patients; 85.7% of these have OSA. The remaining 60 patients present an undetermined pattern. Patients with OSA presented significantly higher maximal positive coherence and maximal negative coherence than those without OSA. We conclude that OSA patients present dynamic coordination and interdependence between SaO(2) and heart rate in specific frequencies.

Adult↗

Lung tissue mechanics and extracellular matrix remodeling in acute lung injury.

UNLABELLED: This study was undertaken to test whether there is structural remodeling of lung parenchyma that could lead to tissue mechanical changes at an early phase of varying degrees of acute lung injury (ALI). Tissue resistance (R), dynamic elastance (E), and hysteresivity (eta) were analyzed during sinusoidal oscillations of rat lung parenchymal strips 24 h after intraperitoneal injection of saline (C) or paraquat (P [10, 15, 25, and 30 mg/kg]). These strips were also stained in order to quantify the amount of collagen and of three types of elastic fibers (elaunin, oxytalan, and fully developed elastic fibers) in the alveolar septa. E augmented progressively from C to P25, but the data from the P25 and P30 groups were not different (p < 0.0001). R and eta increased from C to P10 and from P15 to P25 (p < 0.001). Collagen fiber content increased exponentially with the severity of the injury. Elaunin and fully developed elastic fibers remained unchanged in the five groups, while oxytalan fibers increased only in the P25 and P30 groups. In conclusion, the pronounced mechanical changes at the tissue level and fibroelastogenesis happened at an early phase of the disease and even in mildly abnormal lung parenchyma. KEYWORDS: elastance; collagen fibers; elastin; paraquat

Acute Disease↗

Application of tracheal gas insufflation to acute unilateral lung injury in an experimental model.

In unilateral lung injury, application of global positive end-expiratory pressure (PEEP) may cause overdistension of normal alveoli and redistribution of blood flow to diseased lung areas, thereby worsening oxygenation. We hypothesized that selective application of tracheal gas insufflation (TGI) will recruit the injured lung without causing overdistension of the normal lung. In eight anesthetized dogs, left lung saline lavage was performed until Pa(O(2))/FI(O(2)) fell below 100 mm Hg. Then, the dogs were reintubated with a Univent single lumen endotracheal tube that incorporates an internal catheter to provide TGI. After injury, increasing PEEP from 3 to 10 cm H(2)O did not change gas exchange, hemodynamics, or lung compliance. Selective TGI, while keeping end-expiratory lung volume (EELV) constant, improved Pa(O(2))/FI(O(2)) from 212 +/- 43 to 301 +/- 38 mm Hg (p < 0.01) while Pa(CO(2)) and airway pressures decreased (p < 0.01). During selective TGI, reducing tidal volume to 5.2 ml/kg while keeping EELV constant, normalized Pa(CO(2)), did not affect Pa(O(2))/FI(O(2)), and decreased end-inspiratory plateau pressure from 16.6 +/- 1.0 to 11.9 +/- 0.5 cm H(2)O (p < 0.01). In unilateral lung injury, we conclude that selective TGI (1) improves oxygenation at a lower pressure cost as compared with conventional mechanical ventilation, (2) allows reduction in tidal volume without a change in alveolar ventilation, and (3) may be a useful adjunct to limit ventilator-associated lung injury.

Animals↗

Screening of obstructive sleep apnoea: heart rate spectral analysis of nocturnal pulse oximetric recording.

Using heart rate spectral analysis of nocturnal pulse oximetry, we prospectively evaluated the utility of this methodology in patients clinically suspected of having obstructive sleep apnoea (OSA). A hundred and ninety-seven outpatients referred with symptoms compatible with the diagnosis of OSA were studied. All participants had nocturnal pulse oximetry performed simultaneously with conventional polysomnography. Power density of heart rate obtained by nocturnal pulse oximetry was analysed using fast Fourier transformation of a Hamming-windowed signal. Recording test results were classified as abnormal (suspicion of OSA) in the presence of a peak in the periodogram between period boundaries 30-70 sec. A normal test result was defined as the absence of the 30-70 sec peak in the periodogram. The total area of the periodogram (S(TOT)), the area enclosed in the periodogram between the period boundaries 30-70 sec (S(30-70)), the area enclosed in the period boundaries 30-70 sec with respect to the total area of the periodogram (S) and the peak amplitude 30-70 sec (PA) were measured. The presence of a peak in the periodogram has a sensitivity of 81.3%, a specificity of 91.5% a positive predictive value of 89.1% and a negative predictive value of 85.1% for OSA diagnosis. The OSA patients were found to have higher values of S(TOT), S(30-70), S and PA than the non OSA patients. Receiver operating characteristics (ROC) curve was constructed at different thresholds of S(TOT), S(30-70) S and PA. For a PA threshold of 10(%)2, heart rate spectra analysis sensitivity for OSA was 58% and specificity was 92%. Furthermore, the positive and negative predictive values for diagnosis of OSA were 87 and 72% respectively. Apnoea hypopnea index (AHI) correlated significantly with S(TOT) (r=0.44; P<0.001), S(30-70) (r=0.59: P<0.001), S (r=0.58; P<0.001) and PA (r=0.58; P<0.001). According to our results, heart rate spectral analys s obtained by nocturnal pulse oximetry and identification of peak in the periodogram between period boundaries 30-70 sec could be useful as a diagnostic technique for OSA patients.

Adult↗

Selective tracheal gas insufflation during partial liquid ventilation improves lung function in an animal model of unilateral acute lung injury.

OBJECTIVE: During unilateral lung injury, we hypothesized that we can improve global lung function by applying selective tracheal gas insufflation (TGI) and partial liquid ventilation (PLV) to the injured lung. DESIGN: Prospective, interventional animal study. SETTING: Animal laboratory in a university hospital. SUBJECTS: Adult mixed-breed dogs. INTERVENTIONS: In six anesthetized dogs, left saline lung lavage was performed until PaO(2)/FiO(2) fell below 100 torr (13.3 kPa). The dogs were then reintubated with a Univent single-lumen endotracheal tube, which incorporates an internal catheter to provide TGI. In a consecutive manner, we studied 1) the application of 10 cm H(2)O of positive end-expiratory pressure (PEEP); 2) instillation of 10 mL/kg of perflubron (Liquivent) to the left lung at a PEEP level of 10 cm H(2)O (PLV+PEEP 10 initial); 3) application of selective TGI (PLV+TGI) while maintaining end-expiratory lung volume (EELV) constant; 4) PLV+TGI at reduced tidal volume (VT); and 5) PLV+PEEP 10 final. MEASUREMENTS AND MAIN RESULTS: Application of PLV+PEEP 10 initial did not change gas exchange, lung mechanics, or hemodynamics. PLV+TGI improved PaO(2)/FiO(2) from 189 +/- 13 torr (25.2 +/- 1.7 kPa) to 383 +/- 44 torr (51.1 +/- 5.9 kPa) (p <.01) and decreased PaCO(2) from 55 +/- 5 torr (7.3 +/- 0.7 kPa) to 30 +/- 2 torr (4.0 +/- 0.3 kPa) (p <.01). During ventilation with PLV+TGI, reducing VT from 15 mL/kg to 3.5 mL/kg while keeping EELV constant decreased PaO(2)/FiO(2) to 288 +/- 49 torr (38.4 +/- 6.5 kPa) (not significant) and normalized PaCO(2). At this stage, end-inspiratory plateau pressure decreased from 19.2 +/- 0.7 cm H(2)O to 13.6 +/- 0.7 cm H(2)O (p <.01). At PLV+PEEP 10 final, measurements returned to those observed at previous baseline stage (PLV+PEEP 10 initial). CONCLUSIONS: During unilateral lung injury, PLV with a moderate PEEP did not improve oxygenation, TGI superimposed on PLV improved gas exchange, and combination of TGI and PLV allowed a 77% reduction in VT without any adverse effect on PaCO(2).

Animals↗

Frequency characteristics of lung tissue strip during passive stretch and induced pneumoconstriction.

To investigate the frequency-dependent changes of lung tissue mechanics during pneumoconstriction, we studied guinea pig subpleural lung strips submitted to a multisinusoidal deformation composed of five equal-amplitude discrete frequencies ranging between 0.2 and 3.1 Hz. Strips were submitted to graded step stretch changes (SS) and to graded histamine stimulation (HS) in organ bath. Elastance, resistance, and hysteresivity were calculated at each frequency. The model accounting for the relationship between the complex Young's modulus and the angular frequency showed that the constant-phase hypothesis was satisfied in SS condition. However, HS modified all parameters in the model, and the constant-phase hypothesis could be rejected for HS of 10(-5) and 10(-3) M. The hysteresivity time course changed with angular frequency, but differently in the HS and SS conditions. Our results agree with a serial disposition of the connective matrix and contractile system in lung tissue. We conclude that pneumoconstriction induced significant structural changes at the level of the connective matrix.

Animals↗

Partial improvement in pulmonary function after successful percutaneous balloon mitral valvotomy.

STUDY OBJECTIVES: This study was performed to assess the changes in pulmonary function after a successful percutaneous balloon mitral valvotomy (PBMV) in 23 consecutive patients with symptomatic mitral stenosis. METHODS AND RESULTS: Lung function preprocedure and postprocedure were evaluated by spirometric flow, static pulmonary volumes, and diffusion capacity of the lung for carbon monoxide (DLCO). At baseline, a reduction in small airways flow (maximal expiratory flow at 50% of vital capacity, 70 +/- 29% of predicted value; maximal expiratory flow at 25% of vital capacity, 55 +/- 26% of predicted value) and an increase in DLCO (118 +/- 29%) and Krough Index (KCO; 123 +/- 29% of predicted value) were observed. PBMV caused an improvement in hemodynamic parameters with an increase in mitral valve area (from 1.0 +/- 0.3 to 1.9 +/- 0.5 cm(2); p < 0.001) and a decrease in left atrial pressure (from 17 +/- 3 to 12 +/- 5 mm Hg; p < 0.001). These changes were associated with a significant increase in FVC (from 2.8 +/- 0.84 to 2.9 +/- 0.80 L; p < 0.05) and in FEV(1) (from 2.2 +/- 0.72 to 2.3 +/- 0.68 L; p < 0.05). A decrease in DLCO was observed after PBMV (from 26.7 +/- 7 to 22.5 +/- 5.4 mL/min/mm Hg; p < 0.001; and KCO, from 6.2 +/- 1.4 to 5.2 +/- 1.2 mL/min/mm Hg/L; p < 0.001). No significant changes in small airways flow were detected, suggesting only a partial improvement in pulmonary congestion. CONCLUSION: We conclude that the initial impairment of lung function in patients with symptomatic mitral stenosis is only partially ameliorated by PBMV.

Adult↗

Volumetric capnography in patients with acute lung injury: effects of positive end-expiratory pressure.

The aim of the study was to analyse the effects of positive end-expiratory pressure (PEEP) on volumetric capnography and respiratory system mechanics in mechanically ventilated patients. Eight normal subjects (control group), nine patients with moderate acute lung injury (ALI group) and eight patients with acute respiratory distress syndrome (ARDS group) were studied. Respiratory system mechanics, alveolar ejection volume as a fraction of tidal volume (VAE/VT), phase III slopes of expired CO2 beyond VAE and Bohr's dead space (VD/VT(Bohr)) at different levels of PEEP were measured. No differences in respiratory system resistances were found between the ALI and ARDS groups. VD/VT(Bohr) and expired CO2 slope beyond VAE were higher in ALI patients (0.52+/-0.01 and 13.9+/-0.7 mmHg x L(-1), respectively) compared with control patients (0.46+/-0.01 and 7.7+/-0.4 mmHg x L(-1), p<0.01, respectively) and in ARDS patients (0.61+/-0.02 and 24.9+/-1.6 mmHg x L(-1), p<0.01, respectively) compared with ALI patients. VAE/VT differed similarly (0.6+/-0.01 in control group, 0.43+/-0.01 in ALI group and 0.31+/-0.01 in ARDS group, p<0.01). PEEP had no effect on VAE/VT, expired CO2 slope beyond VAE and VD/VT(Bohr) in any group. A significant correlation (p<0.01) was found between VAE/VT and expired CO2 slope beyond VAE and lung injury score at zero PEEP. Indices of volumetric capnography are affected by the severity of the lung injury, but are unmodified by the application of positive end-expiratory pressure.

Adult↗

Oximetry spectral analysis in the diagnosis of obstructive sleep apnoea.

Using spectral analysis of oximetry data, we prospectively evaluated the validity of this methodology in patients clinically suspected of suffering from obstructive sleep apnoea (OSA). A total of 233 outpatients were studied. Nocturnal oximetry was performed simultaneously with conventional polysomnography for all participants. The power density of oxygen saturation was analysed using Fast-Fourier transformation of the oximetric signal. Nocturnal oximetry test results were considered as abnormal (suspicion of OSA) if a peak in the spectrum between the period boundaries 30 and 70 s was observed. A normal test result was defined as the absence of the 30-70 s peak from the spectrum. Single-blind evaluation was performed by three independent observers, and agreement of two or more of these was considered definitive. The peak amplitude and the ratio of the area enclosed in the 30-70 s peak to the total area of the spectrum (r(S)) were measured. The presence of a peak has a sensitivity of 78%, a specificity of 89%, a positive predictive value of 89% and a negative predictive value of 78%. Apnoea-hypopnoea indexes were correlated significantly with peak amplitude (r=0.74; P<0.001) and with r(S) (r=0.69; P<0.001). For a peak amplitude threshold of 0.7%(2), the sensitivity was 94% and the specificity was 65% for OSA diagnosis. Using a threshold for r(S) of 0.15, the sensitivity was 91% and the specificity was 67%. Thus the spectral analysis of nocturnal oximetry and identification of a peak at 30-70 s could be useful as a diagnostic technique for OSA subjects.

Adult↗

Effect of elastase pretreatment on rat lung strip induced constriction.

On exposure to contractile agonists, peripheral smooth muscle shortens and induces distortion in lung parenchyma. To assess the influence of elastic integrity on lung tissue constriction, 24 rat lung strips were oscillated in organ bath, at a fixed frequency of 1 Hz, and exposed to acetylcholine (Ach) 10(-1) M, before and after incubation with pancreatic porcine elastase (PPE). Before the post-PPE Ach challenge, 11 samples were re-stretched to recover control elastance value. Tissue elastance (Etis), resistance (Rtis), and minimum stress (sigma(min)) were calculated cycle-by-cycle. PPE exposure significantly decreased Etis by 8.50+/-1.91%, and sigma(min) by 33.2+/-3.6%. PPE digestion affected the dynamic of mechanical changes during constriction in non re-stretched samples, but not in re-stretched ones. We conclude that lung tissue damage induced by PPE impairs the transmission of forces generated by lung tissue constriction, challenging mechanical interdependence. The intrinsic properties of contractile machinery seem unaffected by PPE digestion.

Acetylcholine↗

Parallel airways inhomogeneity and lung tissue mechanics in transition to constricted state in rabbits.

To investigate whether changes of tissue resistance (Rti) during methacholine (MCh)-induced constriction correspond to an intrinsic mechanism or are an artifact of increased airways inhomogeneity, rabbits were studied after exposure to air (n = 7) or 1.5 parts/million O3 (n = 6). Animals were anesthetized and mechanically ventilated. Tracheal flow and pressure (Ptr) and four alveolar capsule pressures (Pcap) were measured during 3 min after administration of an intrajugular bolus of 0.8 mg/ml MCh. By adjustment of the equation of motion [P(t) = E . V(t) + R . dV(t)/dt + P0] [where P(t), V(t), and dV(t)/dt are pressure, volume, and flow as a function of time, respectively, E is elastance, R is resistance, and P0 is end-expiratory pressure] to Ptr, lung resistance (RL) and dynamic elastance (EL) were determined breath by breath. Rti and airways resistance (Raw) were determined from Pcap in phase with rate of change of pulmonary expansion. Hysteresivity (eta) was calculated. Parallel inhomogeneity was estimated from the coefficients of variation (CV) of every Pcap at end inspiration and end expiration. Increase in CV significantly lagged Rti, RL, and eta. A linear relationship between EL and Raw was observed. Our results suggest that changes in tissue mechanics during the transition to the constricted state are not artifactual.

Airway Resistance↗

Physiologically based indices of volumetric capnography in patients receiving mechanical ventilation.

Several indices of ventilatory heterogeneity can be identified from the expiratory CO2 partial pressure or CO2 elimination versus volume curves. The aims of this study were: 1) to analyse several computerizable indices of volumetric capnography in order to detect ventilatory disturbances; and 2) to establish the relationship between those indices and respiratory system mechanics in subjects with normal lungs and in patients with acute respiratory distress syndrome (ARDS), both receiving mechanical ventilation. We studied six normal subjects and five patients with early ARDS mechanically ventilated at three levels of tidal volume (VT). Respiratory system mechanics were assessed by end-expiratory and end-inspiratory occlusion methods, respectively. We determined Phase III slopes, Fletcher's efficiency index, Bohr's dead space (VD,Bohr/VT), and the ratio of alveolar ejection volume to tidal volume (VAE/VT) from expiratory capnograms, as a function of expired volume. Differences between normal subjects and ARDS patients were significant both for capnographic and mechanical parameters. Changes in VT significantly altered capnographic indices in normal subjects, but failed to change ventilatory mechanics and VAE/VT in ARDS patients. After adjusting for breathing pattern, VAE/VT exhibited the best correlation with the mechanical parameters. In conclusion, volumetric capnography, and, specifically, the ratio of alveolar ejection volume to tidal volume allows evaluation and monitoring of ventilatory disturbances in patients with adult respiratory distress syndrome.

Adult↗

Transitional effects of inspired CO2 on lung mechanics in anesthetized rabbits.

In eight anesthetized, spontaneously breathing New Zealand rabbits airflow, tidal volume, tracheal and esophageal pressures were measured. Frequency, inspiratory and expiratory durations, respiratory system and lung resistances, and elastances, total postinspiratory muscle pressure and its timing parameters were determined. The measurements were performed: (a) under control condition; (b) continuously, during the first 90 sec of the inhalation of a mixture of 5% CO2 + 95% O2, (carbogen, CI); and (c) 6 min after the start of CI. During CI both lung resistance and elastance decreased, and inspiratory driving pressure and postinspiratory muscle pressure increased. No modification could be detected in either the pattern or the duration of postinspiratory muscle activity. In conclusion, mechanical changes precede and facilitate the ventilatory adjustment to CO2 in rabbits.

Anesthesia↗

Relationship between respiratory mechanics and postinspiratory muscle activity during muscarinic challenge in rabbits.

In six spontaneously breathing New Zealand rabbits (weight 2.36 +/- 0.29 kg) anesthetized with pentobarbital sodium (35 mg/kg i.v.) airflow, tidal volume, and tracheal and esophageal pressures were measured. These allowed the determination of breathing pattern parameters, respiratory system and lung resistances, elastances, and time constants, total postinspiratory muscle pressure and its timing parameters. The measurements were performed: (a) under control conditions; (b) after increasing concentrations of aerosolized methacholine (8, 16, 32, and 64 mg/ml); and (c) after aerosolized atropine (1 mg/ml). Methacholine progressively increased intrinsic mechanical load (resistance and elastance) of the respiratory system. Total postinspiratory muscle pressure (Pmus,0) increased in relation to the increase in elastic load. The duration of postinspiratory activity increased mainly because of the decrease in expiratory time. In conclusion, increase in inspiratory activity during expiration is due to two independent mechanisms controlling the amplitude and the relative duration.

Airway Resistance↗

[A phonogramic study of expiratory wheezing in the asthmatic patient].

UNLABELLED: The quantitative analysis of expiratory wheezing may offer a new approach for study respiratory function in asthmatics. METHOD: The sound spectrum during expiration was analyzed in 9 asthmatics with wheezing and 5 normal subjects. Phonographic parameters were then correlated with spirometric results for baseline respiration and deep breathing. RESULTS: a) Expiratory wheezing is heard in a band of 210 to 280 Hz during deep breathing, and b) the volume in this band correlates positively with mean expiratory flow (VT/TE) and negatively with the slope of the volume/flow curve between 50 and 25% of FVC. CONCLUSIONS: The degree of air flow limitation in the peripheral airways correlates with the volume of pulmonary sound.

Adolescent↗