Ventilation with high tidal volume induces inflammatory lung injury

Mechanical ventilation with high tidal volumes (V T) has been shown to induce lung injury. We examined the hypothesis that this procedure induces lung injury with inflammatory features. Anesthetized male Wistar rats were randomized into three groups: group 1 (N = 12): V T = 7 ml/kg, respiratory rate (RR) = 50 breaths/min; group 2 (N = 10): V T = 21 ml/kg, RR = 16 breaths/min; group 3 (N = 11): V T = 42 ml/kg, RR = 8 breaths/min. The animals were ventilated with fraction of inspired oxygen of 1 and positive end-expiratory pressure of 2 cmH2O. After 4 h of ventilation, group 3, compared to groups 1 and 2, had lower PaO2 [280 (range 73-458) vs 517 (range 307-596), and 547 mmHg (range 330-662), respectively, P<0.05], higher wet lung weight [3.62 ± 0.91 vs 1.69 ± 0.48 and 1.44 ± 0.20 g, respectively, P<0.05], and higher wet lung weight/dry lung weight ratio [18.14 (range 11.55-26.31) vs 7.80 (range 4.79-12.18), and 6.34 (range 5.92-7.04), respectively, P<0.05]. Total cell and neutrophil counts were higher in group 3 compared to groups 1 and 2 (P<0.05), as were baseline TNF-alpha concentrations [134 (range <10-386) vs 16 (range <10-24), and 17 pg/ml (range <10-23), respectively, P<0.05]. Serum TNF-alpha concentrations reached a higher level in group 3, but without statistical significance. These results suggest that mechanical ventilation with high V T induces lung injury with inflammatory characteristics. This ventilatory strategy can affect the release of TNF-alpha in the lungs and can reach the systemic circulation, a finding that may have relevance for the development of a systemic inflammatory response.

Pentoxifylline decreases tumor necrosis factor and interleukin-1 during high tidal volume

Tumor necrosis factor-alpha (TNF-alpha) is one of the most important proinflammatory cytokines which plays a central role in host defense and in the acute inflammatory response related to tissue injury. The major source of TNF-alpha are immune cells such as neutrophils and macrophages. We tested the hypothesis that pentoxifylline, a methylxanthine derivative, down-regulates proinflammatory cytokine expression during acute lung injury in rats. Male Wistar rats weighing 250 to 450 g were anesthetized ip with 50 mg/kg sodium thiopental and randomly divided into three groups: group 1 (N = 7): tidal volume (V T) = 7 ml/kg, respiratory rate (RR) = 50 breaths/min and normal saline infusion; group 2 (N = 7): V T = 42 ml/kg, RR = 9 breaths/min and normal saline infusion; group 3 (N = 7): V T = 42 ml/kg, RR = 9 breaths/min and pentoxifylline infusion. The animals were ventilated with an inspired oxygen fraction of 1.0, a positive end-expiratory pressure of 3 cmH2O, and normal saline or pentoxifylline injected into the left femoral vein. The mRNA of TNF-alpha rapidly increased in the lung tissue within 180 min of ventilation with a higher V T with normal saline infusion. The concentrations of inflammatory mediators were decreased in plasma and bronchoalveolar lavage (BAL) in the presence of higher V T with pentoxifylline infusion (TNF-alpha: plasma, 102.2 ± 90.9 and BAL, 118.2 ± 82.1; IL-1ß: plasma, 45.2 ± 42.7 and BAL, 50.2 ± 34.9, P < 0.05). We conclude that TNF-alpha produced by neutrophil influx may function as an alert signal in host defense to induce production of other inflammatory mediators.

Glomerular filtration is reduced by high tidal volume ventilation in an in vivo healthy rat model

Mechanical ventilation has been associated with organ failure in patients with acute respiratory distress syndrome. The present study examines the effects of tidal volume (V T) on renal function using two V T values (8 and 27 mL/kg) in anesthetized, paralyzed and mechanically ventilated male Wistar rats. Animals were randomized into two groups of 6 rats each: V T8 (V T, 8 mL/kg; 61.50 ± 0.92 breaths/min; positive end-expiratory pressure, 3.0 cmH2O; peak airway pressure (PAW), 11.8 ± 2.0 cmH2O), and V T27 (V T, 27 mL/kg; 33.60 ± 1.56 breaths/min; positive end-expiratory pressure, none, and PAW, 22.7 ± 4.0 cmH2O). Throughout the experiment, mean PAW remained comparable between the two groups (6.33 ± 0.21 vs 6.50 ± 0.22 cmH2O). For rats in the V T27 group, inulin clearance (mL·min-1·body weight-1) decreased acutely after 60 min of mechanical ventilation and even more significantly after 90 min, compared with baseline values (0.60 ± 0.05 and 0.45 ± 0.05 vs 0.95 ± 0.07; P < 0.001), although there were no differences between groups in mean arterial pressure or gasometric variables. In the V T8 group, inulin clearance at 120 min of mechanical ventilation remained unchanged in relation to baseline values (0.72 ± 0.03 vs 0.80 ± 0.05). The V T8 and V T27 groups did not differ in terms of serum thiobarbituric acid reactive substances (3.97 ± 0.27 vs 4.02 ± 0.45 nmol/mL) or endothelial nitric oxide synthase expression (94.25 ± 2.75 vs 96.25 ± 2.39%). Our results show that glomerular filtration is acutely affected by high tidal volume ventilation but do not provide information about the mechanism.

Assessment of tidal volume and thoracoabdominal motion using volume and flow-oriented incentive spirometers in healthy subjects

The objective of the present study was to evaluate incentive spirometers using volume- (Coach and Voldyne) and flow-oriented (Triflo II and Respirex) devices. Sixteen healthy subjects, 24 ± 4 years, 62 ± 12 kg, were studied. Respiratory variables were obtained by respiratory inductive plethysmography, with subjects in a semi-reclined position (45º). Tidal volume, respiratory frequency, minute ventilation, inspiratory duty cycle, mean inspiratory flow, and thoracoabdominal motion were measured. Statistical analysis was performed with Kolmogorov-Smirnov test, t-test and ANOVA. Comparison between the Coach and Voldyne devices showed that larger values of tidal volume (1035 ± 268 vs 947 ± 268 ml, P = 0.02) and minute ventilation (9.07 ± 3.61 vs 7.49 ± 2.58 l/min, P = 0.01) were reached with Voldyne, whereas no significant differences in respiratory frequency were observed (7.85 ± 1.24 vs 8.57 ± 1.89 bpm). Comparison between flow-oriented devices showed larger values of inspiratory duty cycle and lower mean inspiratory flow with Triflo II (0.35 ± 0.05 vs 0.32 ± 0.05 ml/s, P = 0.00, and 531 ± 137 vs 606 ± 167 ml/s, P = 0.00, respectively). Abdominal motion was larger (P < 0.05) during the use of volume-oriented devices compared to flow-oriented devices (52 ± 11% for Coach and 50 ± 9% for Voldyne; 43 ± 13% for Triflo II and 44 ± 14% for Respirex). We observed that significantly higher tidal volume associated with low respiratory frequency was reached with Voldyne, and that there was a larger abdominal displacement with volume-oriented devices.

Standardization of pulmonary ventilation technique using volume-controlled ventilators in rats with congenital diaphragmatic hernia

OBJECTIVE: To standardize a technique for ventilating rat fetuses with Congenital Diaphragmatic Hernia (CDH) using a volume-controlled ventilator.METHODS: Pregnant rats were divided into the following groups: a) control (C); b) exposed to nitrofen with CDH (CDH); and c) exposed to nitrofen without CDH (N-). Fetuses of the three groups were randomly divided into the subgroups ventilated (V) and non-ventilated (N-V). Fetuses were collected on day 21.5 of gestation, weighed and ventilated for 30 minutes using a volume-controlled ventilator. Then the lungs were collected for histological study. We evaluated: body weight (BW), total lung weight (TLW), left lung weight (LLW), ratios TLW / BW and LLW / BW, morphological histology of the airways and causes of failures of ventilation.RESULTS: BW, TLW, LLW, TLW / BW and LLW / BW were higher in C compared with N- (p <0.05) and CDH (p <0.05), but no differences were found between the subgroups V and N-V (p> 0.05). The morphology of the pulmonary airways showed hypoplasia in groups N- and CDH, with no difference between V and N-V (p <0.05). The C and N- groups could be successfully ventilated using a tidal volume of 75 ìl, but the failure of ventilation in the CDH group decreased only when ventilated with 50 ìl.CONCLUSION: Volume ventilation is possible in rats with CDH for a short period and does not alter fetal or lung morphology.

Participation of nitric oxide in the nucleus isthmi in CO2-drive to breathing in toads

The nucleus isthmi (NI) is a mesencephalic structure of the amphibian brain. It has been reported that NI plays an important role in integration of CO2 chemoreceptor information and glutamate is probably involved in this function. However, very little is known about the mechanisms involved. Recently, it has been shown that nitric oxide synthase (NOS) is expressed in the brain of the frog. Thus the gas nitric oxide (NO) may be involved in different functions in the brain of amphibians and may act as a neurotransmitter or neuromodulator. We tested the hypothesis that NO plays a role in CO2-drive to breathing, specifically in the NI comparing pulmonary ventilation, breathing frequency and tidal volume, after microinjecting 100 nmol/0.5 µl of L-NAME (a nonselective NO synthase inhibitor) into the NI of toads (Bufo paracnemis) exposed to normocapnia and hypercapnia. Control animals received microinjections of vehicle of the same volume. Under normocapnia no significant changes were observed between control and L-NAME-treated toads. Hypercapnia caused a significant (P<0.01) increase in ventilation only after intracerebral microinjection of L-NAME. Exposure to hypercapnia caused a significant increase in breathing frequency both in control and L-NAME-treated toads (P<0.01 for the control group and P<0.001 for the L-NAME group). The tidal volume of the L-NAME group tended to be higher than in the control group under hypercapnia, but the increase was not statistically significant. The data indicate that NO in the NI has an inhibitory effect only when the respiratory drive is high (hypercapnia), probably acting on tidal volume. The observations reported in the present investigation, together with other studies on the presence of NOS in amphibians, indicate a considerable degree of phylogenetic conservation of the NO pathway amongst vertebrates.

Different doses of exogenous surfactant for treatment of meconium aspiration syndrome in newborn rabbits

OBJECTIVE: To evaluate the effects of 2 different doses of exogenous surfactant on pulmonary mechanics and on the regularity of pulmonary parenchyma inflation in newborn rabbits. METHOD: Newborn rabbits were submitted to tracheostomy and randomized into 4 study groups: the Control group did not receive any material inside the trachea; the MEC group was instilled with meconium, without surfactant treatment; the S100 and S200 groups were instilled with meconium and were treated with 100 and 200 mg/kg of exogenous surfactant (produced by Instituto Butantan) respectively. Animals from the 4 groups were mechanically ventilated during a 25-minute period. Dynamic compliance, ventilatory pressure, tidal volume, and maximum lung volume (P-V curve) were evaluated. Histological analysis was conducted using the mean linear intercept (Lm), and the lung tissue distortion index (SDI) was derived from the standard deviation of the means of the Lm. One-way analysis of variance was used with a = 0.05. RESULTS: After 25 minutes of ventilation, dynamic compliance (mL/cm H2O · kg) was 0.87 ± 0.07 (Control); 0.49 ± 0.04 (MEC*); 0.67 ± 0.06 (S100); and 0.67 ± 0.08 (S200), and ventilatory pressure (cm H2O) was 9.0 ± 0.9 (Control); 16.5 ± 1.7 (MEC*); 12.4 ± 1.1 (S100); and 12.1 ± 1.5 (S200). Both treated groups had lower Lm values and more homogeneity in the lung parenchyma compared to the MEC group: SDI = 7.5 ± 1.9 (Control); 11.3 ± 2.5 (MEC*), 5.8 ± 1.9 (S100); and 6.7 ± 1.7 (S200) (*P < 0.05 versus all the other groups). CONCLUSIONS: Animals treated with surfactant showed significant improvement in pulmonary mechanics and more regularity of the lung parenchyma in comparison to untreated animals. There was no difference in results after treatment with either of the doses used.

Assessment of factors that influence weaning from long-term mechanical ventilation after cardiac surgery

OBJECTIVE: To analyze parameters of respiratory system mechanics and oxygenation and cardiovascular alterations involved in weaning tracheostomized patients from long-term mechanical ventilation after cardiac surgery. METHODS: We studied 45 patients in their postoperative period of cardiac surgery, who required long-term mechanical ventilation for more than 10 days and had to undergo tracheostomy due to unsuccessful weaning from mechanical ventilation. The parameters of respiratory system mechanics, oxigenation and the following factors were analyzed: type of surgical procedure, presence of cardiac dysfunction, time of extracorporeal circulation, and presence of neurologic lesions. RESULTS: Of the 45 patients studied, successful weaning from mechanical ventilation was achieved in 22 patients, while the procedure was unsuccessful in 23 patients. No statistically significant difference was observed between the groups in regard to static pulmonary compliance (p=0.23), airway resistance (p=0.21), and the dead space/tidal volume ratio (p=0.54). No difference was also observed in regard to the variables PaO2/FiO2 ratio (p=0.86), rapid and superficial respiration index (p=0.48), and carbon dioxide arterial pressure (p=0.86). Cardiac dysfunction and time of extracorporeal circulation showed a significant difference. CONCLUSION: Data on respiratory system mechanics and oxygenation were not parameters for assessing the success or failure. Cardiac dysfunction and time of cardiopulmonary bypass, however, significantly interfered with the success in weaning patients from mechanical ventilation.

Estudo da adsorção de compostos sulfurados empregando zeólitas contendo zinco

This paper deals with an adosrption of sulphur compounds employing zeolites containing zinc. The zeolites employed were commercial NaY and Beta. The zinc was incorporated in three levels: 0.5; 1.0 and 5%. The sulphur compounds studied were benzothiophene and dibenzothiofene. The results showed that both zeolites can be employed for adsorption of benzothiophene and dibenzothiophene. The Zn incorporation (0.5%) promotes an increase in zeolites adsorption ability. The DBT adsorbs more than BT, probably because it strongly interacts with zeolite structure. The BT adsorbs more in NaY than in beta probably because the NaY zeolite has a high intern volume. This is not observed for DBT.

Nanotecnologia: aspectos gerais e potencial de aplicação em catálise

In recent years nanomaterials, such as metallic nanoparticles, nanowires, nanotapes, nanotubes and nanocomposites, have attracted increasing interest for several technological applications. In catalysis, the great potential of nanomaterials is related to the high catalytic activity exhibited by these materials as a function of the high surface/volume ratio when the particles acquire diameter below 5 nm. In this work, a review about concepts and background of nanoscience and nanotechnology is presented with emphasis in catalysis. Special attention is given to gold nanoparticles and carbon nanotubes, focusing the properties and characteristics of these materials in several catalytic reactions.

Pulmonar recruitment in acute respiratory distress syndrome. What is the best strategy?

Supporting patients with acute respiratory distress syndrome (ARDS), using a protective mechanical ventilation strategy characterized by low tidal volume and limitation of positive end-expiratory pressure (PEEP) is a standard practice in the intensive care unit. However, these strategies can promote lung de-recruitment, leading to the cyclic closing and reopening of collapsed alveoli and small airways. Recruitment maneuvers (RM) can be used to augment other methods, like positive end-expiratory pressure and positioning, to improve aerated lung volume. Clinical practice varies widely, and the optimal method and patient selection for recruitment maneuvers have not been determined, considerable uncertainty remaining regarding the appropriateness of RM. This review aims to discuss recent findings about the available types of RM, and compare the effectiveness, indications and adverse effects among them, as well as their impact on morbidity and mortality in ARDS patients. Recent developments include experimental and clinical evidence that a stepwise extended recruitment maneuver may cause an improvement in aerated lung volume and decrease the biological impact seen with the traditionally used sustained inflation, with less adverse effects. Prone positioning can reduce mortality in severe ARDS patients and may be an useful adjunct to recruitment maneuvers and advanced ventilatory strategies, such noisy ventilation and BIVENT, which have been useful in providing lung recruitment.

Effect of ventilation on systemic blood flow evaluated by echodopplercardiography

Systemic blood flow (Q) was measured by echodopplercardiography in 5 normal young adult males during apnea, eupnea and tachypnea. Measurements were made in a recumbent posture at 3-min intervals. Tachypnea was attained by doubling the respiratory frequency at eupnea at a constant tidal volume. An open glottis was maintained during apnea at the resting respiratory level. The Q values were positively correlated with the respiratory frequency, decreasing from eupnea to apnea and increasing from eupnea to tachypnea (P<0.05). These data demonstrate that echodopplercardiography, a better qualified tool for this purpose, confirms the positive and progressive effects of ventilation on systemic blood flow, as suggested by previous studies based on diverse technical approaches

Lung tissue mechanics in the early stages of induced paracoccidioidomycosis in rats

Pulmonary dysfunction represents the most important cause of death in patients with paracoccidioidomycosis (PBM). In order to investigate the functional changes of the lungs in the early stages of PBM, a model of benign disease was developed by intratracheal challenge of 12-week old isogenic Wistar rats with 1 x 106 yeast forms of Paracoccidioides brasiliensis. Animals were studied 30 and 60 days after infection, when fully developed granulomas were demonstrable in the lungs. Measurements of airway resistance, lung elastance and tissue hysteresis were made during sinusoidal deformations (100 breaths/min, tidal volume = 2 ml) with direct measurement of alveolar pressure using the alveolar capsule technique. Infection caused a significant increase in hysteresis (infected: 1.69, N = 13; control: 1.13, N = 12, P = 0.024, ANOVA), with no alterations in airway resistance or lung elastance. Histopathological analysis revealed the presence of fully developed granulomas located in the axial compartment of the lung interstitial space. These results suggest that alterations of tissue mechanics represent an early event in experimental PBM

Cardiovascular and respiratory changes during slow-wave sleep in rats are associated with electrocorticogram desynchronization

In awake rats a single recurrent larger tidal volume (deep breaths) occurs at regular intervals, followed by oscillations in arterial pressure and heart rate. In the present study we recorded the changes in blood pressure, heart rate and ventilation during the wakefulness-sleep cycle identified by electrocorticographic records in order to determine whether the deep breaths and cardiovascular oscillations were associated with changes in the electrocorticogram. During several episodes of slow-wave sleep (SWS) in 7 rats the deep breaths and oscillations in arterial pressure and heart rate were preceded by SWS desynchronization. The interval between deep breaths during SWS was 71 ± 4 s, the period between initial desynchronization and the generation of deep breaths was 3.98 ± 0.45 s and the duration of SWS desynchronization was 11 ± 0.65 s. Hypotension (-16 ± 1 mmHg) and tachycardia (+15 ± 5 bpm) were observed during deep breaths in the SWS state. These data indicate that the oscillations in arterial pressure and heart rate during SWS are associated with deep breaths, which in turn are preceded by desynchronization of the electrocorticogram in this state of sleep

Respiratory effects of kynurenic acid microinjected into the ventromedullary surface of the rat

Several studies demonstrate that, within the ventral medullary surface (VMS), excitatory amino acids are necessary components of the neural circuits involved in the tonic and reflex control of respiration and circulation. In the present study we investigated the cardiorespiratory effects of unilateral microinjections of the broad spectrum glutamate antagonist kynurenic acid (2 nmol/200 nl) along the VMS of urethane-anesthetized rats. Within the VMS only one region was responsive to this drug. This area includes most of the intermediate respiratory area, partially overlapping the rostral ventrolateral medulla (IA/RVL). When microinjected into the IA/RVL, kynurenic acid produced a respiratory depression, without changes in mean arterial pressure or heart rate. The respiratory depression observed was characterized by a decrease in ventilation, tidal volume and mean inspiratory flow and an increase in respiratory frequency. Therefore, the observed respiratory depression was entirely due to a reduction in the inspiratory drive. Microinjections of vehicle (200 nl of saline) into this area produced no significant changes in breathing pattern, blood pressure or heart rate. Respiratory depression in response to the blockade of glutamatergic receptors inside the rostral VMS suggests that neurons at this site have an endogenous glutamatergic input controlling the respiratory cycle duration and the inspiratory drive transmission.