Barotrauma and microvascular injury in lungs of nonadult rabbits: effect of ventilation pattern

To study the pulmonary microvascular injury produced by ventilation barotrauma, the isolated perfused lungs of 4 to 6-wk-old New Zealand white rabbits were ventilated by one of the following methods: peak inspiratory pressure (PIP) 23 cm H2O, gas flow rate 1.1 L/min (group 1); PIP 27 cm H2O, gas flow rate 6.9 L/min (group 2); PIP 50 cm H2O, gas flow rate 1.9 L/min (group 3); or PIP 53 cm H2O, gas flow rate 8.3 L/min (group 4). Microvascular permeability was assessed using the capillary filtration coefficient (Kfc) before and 5, 30, and 60 min after a 15-min period of ventilation. Baseline Kfc was not significantly different between groups. A significant increase over the baseline Kfc was noted at 60 min in group 2 and in all postventilation Kfc values in groups 3 and 4 (p less than .05). Group 1 Kfc values did not change significantly after ventilation. At all post-ventilation times, values for Kfc were significantly greater in groups 3 and 4 than in group 1 (p less than .05). Group 4 Kfc values were significantly greater than those in group 2 at 5 and 30 min postventilation. These data indicate that high PIP, and to a lesser extent, high gas flow rates cause microvascular injury in the compliant nonadult lung and suggest that the combination of high PIP and high gas flow rates are the most threatening to microvascular integrity.     

Increased sensitivity to mechanical ventilation after surfactant inactivation in young rabbit lungs.

OBJECTIVES: To study the individual and combined effects of surfactant inactivation and mechanical ventilation on pulmonary microvascular permeability and lung compliance. DESIGN: Prospective, controlled trial. An isolated, perfused, lung model of surfactant inactivation and mechanical ventilation at 15, 30, and 45 cm H2O peak inspiratory pressure was developed in young (4 to 6 wks) New Zealand white rabbits. SETTING: Laboratory of a university-affiliated medical school. MEASUREMENTS AND MAIN RESULTS: Isolated, perfused lungs were prepared for measurement of the capillary filtration coefficient before and after one of four interventions: instillation of dioctyl succinate, a surfactant inactivator, without ventilation (group 1); ventilation without dioctyl succinate at 15, 30, or 45 cm H2O peak inspiratory pressure (group 2); ventilation after dioctyl succinate pretreatment at 15, 30, or 45 cm H2O peak inspiratory pressure (group 3); and control lungs without dioctyl succinate or ventilation (group 4). A significant increase in the capillary filtration coefficient was noted after dioctyl succinate treatment alone, after ventilation alone at 45 cm H2O peak inspiratory pressure, and after dioctyl succinate plus ventilation at 15, 30, and 45 cm H2O peak inspiratory pressure. Dioctyl succinate plus ventilation produced a significantly greater increase in the capillary filtration coefficient than ventilation alone at 15 and 45 cm H2O peak inspiratory pressure. CONCLUSIONS: These data suggest that ventilation after surfactant inactivation is more injurious to the pulmonary microvasculature than ventilation alone, and that generalized lung overdistention is not the primary mechanism for microvascular injury in the diseased, noncompliant lung. The increases seen in the capillary filtration coefficient in postventilated surfactant inactivated lungs, even at low-ventilation pressures, suggest that low peak inspiratory pressures do not overdistend the dioctyl succinate-treated lung.     

Protective effects of low respiratory frequency in experimental ventilator-associated lung injury

OBJECTIVE: To determine whether ventilator-associated lung hyperinflation injury can be attenuated by a reduction in respiratory frequency. DESIGN: Prospective comparative laboratory investigation. SETTING: University medical center research laboratory. SUBJECTS: Male Sprague-Dawley rats. INTERVENTIONS: Eight groups of isolated, perfused rat lungs were exposed to cyclic ventilation at different respiratory frequencies and tidal volumes. Each group of six to eight lung preparations was assigned to one of four respiratory frequencies (10, 20, 40, or 80 breaths/min) and one of two tidal volumes (5 or 20 mL.kg). Measurement of capillary filtration coefficient (Kf,c), a sensitive index of lung microvascular permeability and injury, was made at baseline and at 30, 60, and 90 mins of the experimental conditions. MEASUREMENTS AND MAIN RESULTS: Lungs exposed to 5 mL.kg tidal volume had no elevation in Kf,c at any time point regardless of respiratory frequency. Lungs exposed to 20 mL. kg tidal volume and a respiratory frequency of 80 had significant elevations in Kf,c at all times after baseline compared with lungs exposed to respiratory frequencies of 10, 20, or 40 (0.14 +/- 0.03, 0.16 +/- 0.02, 0.31 +/- 0.05 vs. 0.76 +/- 0.16). Furthermore, the Kf,c at 90 mins was significantly higher than permeability at baseline in this group (1.53 +/- 0.45 vs. 0.12 +/- 0.02 mL.min.cm H2O.100 g of lung tissue). CONCLUSIONS: Reduction in respiratory frequency to values much lower than normal ameliorated experimental ventilator-induced hyperinflation lung injury as determined by pulmonary capillary filtration coefficient.     

Effects of cyclic opening and closing at low- and high-volume ventilation on bronchoalveolar lavage cytokines

OBJECTIVE: To examine the mechanisms of ventilator-induced lung injury at low and high lung volumes. DESIGN: Prospective, randomized, laboratory study. SETTING: University research laboratory. SUBJECTS: Eighty-eight adult male Sprague-Dawley rats. INTERVENTIONS: Mechanical ventilation using low and high lung volumes. MEASUREMENTS AND MAIN RESULTS: An ex vivo rat lung model was used. In study I (ventilation at low lung volumes), rat lungs (n = 40) were randomly assigned to various modes of ventilation: a) opening and closing with positive end-expiratory pressure (PEEP; control): tidal volume 7 mL/kg and PEEP 5 cm H2O; b) opening and closing from zero end-expiratory pressure (ZEEP): tidal volume 7 mL/kg and PEEP 0; or c) atelectasis. Peak inspiratory pressure was monitored at the beginning and end of 3 hrs of ventilation. At the end of 3 hrs of ventilation, the lungs were lavaged, and the concentrations of tumor necrosis factor-alpha, macrophage inflammatory protein-2, and interleukin-6 cytokines were measured in the lavage. In study II (ventilation at high volumes), rat lungs (n = 45) were randomly assigned to a) cyclic lung stretch: pressure-controlled ventilation, peak inspiratory pressure 50 cm H2O, and PEEP 8 cm H2O; b) continuous positive airway pressure at 50 cm H2O (CPAP50); or c) CPAP at the mean airway pressure of the cyclic stretch group (CPAP 31 cm H2O). Bronchoalveolar lavage cytokine concentrations (tumor necrosis factor-alpha, macrophage inflammatory protein-2, and interleukin-6) were measured at the end of 3 hrs of ventilation. In the low volume study, there was no difference in bronchoalveolar lavage cytokine concentrations between the PEEP group and the atelectatic group. All cytokines were significantly higher in the ZEEP group compared with the atelectasis group. Macrophage inflammatory protein-2 was significantly higher in the ZEEP group compared with the PEEP group. Lung compliance, as reflected by change in peak inspiratory pressure, was also significantly worse in the ZEEP compared with the PEEP group. In the high-volume study, tumor necrosis factor-alpha and interleukin-6 were significantly higher in the cyclic stretch group compared with the CPAP 31 group. There was no significant difference between the cytokine concentrations in the cyclic stretch group compared with the CPAP 50 group. CONCLUSION: We conclude that at low lung volumes, cyclic opening and closing from ZEEP leads to greater increases in bronchoalveolar lavage cytokines than atelectasis. With high-volume ventilation, over time, the degree of overdistension is more associated with increases in bronchoalveolar lavage cytokines than cyclic opening and closing alone.     

Adapting prognostic respiratory variables of ARDS in children to small-scale community needs

PURPOSE: The clinical literature on the incidence and subsequent mortality of adult respiratory distress syndrome (ARDS) has come primarily from the experiences of large tertiary referral centers, particularly in Western Europe and North America. Consequently, very little has been published on the incidence, management, and outcome of ARDS in smaller community-based intensive care units. We aimed to delineate early clinical respiratory predictors of death in children with ARDS on the modest scale of a community hospital. MATERIALS AND METHODS: A retrospective chart review of children with ARDS needing conventional mechanical ventilation admitted to our pediatric intensive care unit from 1984 to 1997. The diagnosis of ARDS was based on acute onset of diffuse, bilateral pulmonary infiltrates of noncardiac origin and severe hypoxemia defined by partial pressure of oxygen <200 mm Hg during positive end-expiratory pressure (PEEP) of 6 cm H2O or greater for a minimum of 24 hours. Demographic, clinical, and physiological data including PaO2/ FIO2, A-aDo2, and ventilation index were retrieved. RESULTS: Fifty-six children with ARDS aged 8 +/- 5.5 years (range, 50 days to 21 years) were identified. The mortality rate was 50%. Early predictors of death included the peak inspiratory pressure (PIP), ventilation index, and PEEP on the third day after diagnosis: Nonsurvivors had significantly higher PIP (35.3 +/- 10.5 cm H2O vs 44.4 +/- 10.7 cm H2O, P < .001), PEEP (8 +/- 2.8 cm H2O vs 10.7.0 +/- 3.5 cm H2O, P < .01), and ventilation index (49.14 +/- 20.4 mm Hg x cm H2O/minute vs 61.6 +/- 51.1 mm Hg cm H2O/minute) than survivors. In contrast, PAO2/FIO2 and A-a DO2 were capable of predicting outcome by day 5 and thereafter. CONCLUSIONS: A small-scale mortality outcome for ARDS is comparable to large tertiary referral institutions. The PIP, PEEP, and ventilation index are valuable for predicting outcome in ARDS by the third day of conventional therapy. The development of a local risk profile may assist in decision-making of early application of supportive therapies in this population.     

Pulmonary surfactant is altered during mechanical ventilation of isolated rat lung

OBJECTIVE: To test the hypothesis that the lung injury induced by certain mechanical ventilation strategies is associated with changes in the pulmonary surfactant system. DESIGN: Analysis of the pulmonary surfactant system from isolated rat lungs after one of four different ventilatory strategies. SETTING: A research laboratory at a university. SUBJECTS: A total of 45 Sprague-Dawley rats. INTERVENTIONS: Isolated lungs were randomized to either no ventilation (0-TIME) or to ventilation at 40 breaths/min in a humidified 37 degrees C chamber for either 30 mins or 120 mins with one of the following four strategies: a) control (CON, 7 mL/kg, 3 cm H2O positive end-expiratory pressure); b) medium volume, zero end-expiratory pressure (MVZP, 15 mL/kg, 0 cm H2O end-expiratory pressure); c) medium volume, high positive end-expiratory pressure (MVHP, 15 mL/kg, 9 cm H2O positive end-expiratory pressure); and d) high volume, zero end-expiratory pressure (HVZP, 40 mL/kg, 0 cm H2O end-expiratory pressure). MEASUREMENTS: Pressure-volume curves were determined before and after the ventilation period, after which the lungs were lavaged for surfactant analysis. MAIN RESULTS: Compared with 0-TIME, 30 mins of ventilation with the HVZP strategy or 120 mins of ventilation with CON and MVZP strategies caused a significant decrease in compliance. Groups showing a decreased compliance had significant increases in the amount of surfactant, surfactant large aggregates, and total lavage protein compared with 0-TIME. CONCLUSIONS: A short period of injurious mechanical ventilation can cause a decrease in lung compliance that is associated with a large influx of proteins into the alveolar space and with alterations of the pulmonary surfactant system. The changes of surfactant in these experiments are different from those seen in acute lung injury, indicating that they may represent an initial response to mechanical ventilation.     

Development and application of a double-piston configured, total-liquid ventilatory support device

OBJECTIVE: Perfluorocarbon liquid ventilation has been shown to enhance pulmonary mechanics and gas exchange in the setting of respiratory failure. To optimize the total liquid ventilation process, we developed a volume-limited, time-cycled liquid ventilatory support, consisting of an electrically actuated, microprocessor-controlled, double-cylinder, piston pump with two separate limbs for active inspiration and expiration. DESIGN: Prospective, controlled, animal laboratory study, involving sequential application of conventional gas ventilation, partial ventilation (PLV), and total liquid ventilation (TLV). SETTING: Research facility at a university medical center. SUBJECTS: A total of 12 normal adult New Zealand rabbits weighing 3.25+/-0.1 kg. INTERVENTIONS: Anesthestized rabbits were supported with gas ventilation for 30 mins (respiratory rate, 20 cycles/min; peak inspiratory pressure, 15 cm H2O; end-expiratory pressure, 5 cm H2O), then PLV was established with perflubron (12 mL/kg). After 15 mins, TLV was instituted (tidal volume, 18 mL/kg; respiratory rate, 7 cycles/min; inspiratory/expiratory ratio, 1:2 cycles/min). After 4 hrs of TLV, PLV was re-established. MEASUREMENTS AND MAIN RESULTS: Of 12 animals, nine survived the 4-hr TLV period. During TLV, mean values +/- SEM were as follows: PaO2, 363+/-30 torr; PaCO2, 39+/-1.5 torr; pH, 7.39+/-0.01; static peak inspiratory pressure, 13.2+/-0.2 cm H2O; static endexpiratory pressure, 5.5+/-0.1 cm H2O. No significant changes were observed. When compared with gas ventilation and PLV, significant increases occurred in mean arterial pressure (62.4+/-3.5 torr vs. 74.0+/-1.2 torr) and central venous pressure (5.6+/-0.7 cm H2O vs. 7.8+/-0.2 cm H2O) (p < .05). CONCLUSIONS: Total liquid ventilation can be performed successfully utilizing piston pumps with active expiration. Considering the enhanced flow profiles, this device configuration provides advantages over others.     

A new infant ventilator for normal and high-frequency ventilation: influence of tracheal tube on distal airway pressure during high-frequency ventilation

A new infant ventilator for both normal and high-frequency ventilation is described. High pressure gas delivered via a jet in the breathing limb of a T-piece, in which there are no valves, drives respiratory fresh gas (RFG), supplied to the tracheal tube from any low pressure source, into the lungs. Observations on anesthetized rabbits showed that after setting up for a PaCO2 of 36 torr at 30 cycle/min, it remained around 36 torr when the ventilation frequency was progressively increased to 200 cycle/min. The mean peak proximal airway and tracheal pressures were 13 and 12, 11 and 7, and 13 cm H2O (PEEP 2.1 cm H2O) and 7.4 cm H2O (PEEP 3.1 cm H2O) at 30, 100 and 200 cycle/min, respectively. In this open valveless breathing system, desynchronized spontaneous and artificial ventilation occurred quietly without any marked variation in the airway pressures. This preliminary study on a new pneumatic system shows its potential for simplifying and improving infant ventilation.     

Efficacy of partial liquid ventilation in improving acute lung injury induced by intratracheal acidified infant formula: determination of optimal dose and positive end-expiratory pressure level

OBJECTIVES: Partial liquid ventilation with fluorocarbon was successfully used for acute lung injury induced by oleic acid or lung lavage. Positive end-expiratory pressure (PEEP) during partial liquid ventilation enhances the efficacy of fluorocarbon. The aim of the current study was to assess whether partial liquid ventilation can repair lung damage induced by intratracheal acidified infant formula and to determine the optimal fluorocarbon dose and PEEP level. DESIGN: Prospective, randomized animal study. SETTING: University research laboratory. SETTING AND SUBJECTS: Seventy-six male anesthetized rabbits. INTERVENTIONS: For study 1, acute lung injury was induced by intratracheal acidified infant formula in four groups. Next, three groups received 10, 15, or 20 mL/kg fluorocarbon, and the fourth group was conventionally gas ventilated. For study 2, acute lung injury was induced in five groups. One group was gas ventilated at a PEEP of 5 cm H2O, whereas the other four groups received fluorocarbon (15 mL/kg) and were assigned to one of four PEEP levels (5, 7.5, 10, or 12.5 cm H2O). The lungs were ventilated with 100% oxygen for 4 hrs after acute lung injury. MEASUREMENTS AND MAIN RESULTS: In study 1, fluorocarbon at doses of 15 and 20 mL/kg attenuated lung leukosequestration and edema and superoxide production of neutrophils, resulting in similar improvements in oxygenation, lung mechanics, and pathologic changes. The highest fluorocarbon dose caused mortality from pneumothorax. In study 2, the combination of PEEP with partial liquid ventilation improved gas exchange, lung compliance, pulmonary edema, and histologically observed damage. The beneficial effects of PEEP at 10 and 12.5 cm H2O were similar. Adverse side effects of 12.5 cm H2O PEEP included pneumothorax and hemodynamic instability. CONCLUSIONS: The combination of fluorocarbon and PEEP improved the physiologic, biochemical, and histologic lung injury induced by acidified infant formula. The beneficial effects of partial liquid ventilation are due, in part, to inhibition of pulmonary neutrophil accumulation and activation with fluorocarbon. The optimal fluorocarbon dose and PEEP level in our model were 15 mL/kg and 10 cm H2O, respectively.     

Systemic cardiac output and distribution during high-frequency oscillation

High-frequency oscillation (HFO) appears to be an alternate, less traumatic mode of ventilating surfactant-deficient patients, because conventional (mechanical) pressure-limited ventilation (CMV) compromises cardiac function at high mean airway pressures. We compared systemic cardiac output and its distribution during HFO and CMV in ten adult rabbits rendered surfactant deficient by repeated pulmonary saline lavage. Cardiac output and organ blood flow were measured using the radionucleotide-labeled microsphere technique during ventilation at a mean airway pressure of 15 cm H2O and an inspired oxygen concentration of 100%. Both cardiac output and organ perfusion were similar during both modes of ventilation.     

Effects of mean airway pressure and tidal excursion on lung injury induced by mechanical ventilation in an isolated perfused rabbit lung model.

OBJECTIVE: To study the relative contributions of mean airway pressure (mPaw) and tidal excursion (V(T)) to ventilator-induced lung injury under constant perfusion conditions. DESIGN: Prospective, randomized study. SETTING: Experimental animal laboratory. SUBJECTS: Fifteen sets of isolated rabbit lungs. INTERVENTIONS: Rabbit lungs were perfused (constant flow, 500 mL/min; capillary pressure, 10 mm Hg) and randomized to be ventilated at identical peak transpulmonary pressure (pressure control ventilation [30 cm H2O and frequency of 20/min]) with three different ventilatory patterns that differed from each other by either mPaw or V(T): group A (low mPaw [13.4+/-0.2 cm H2O]/large V(T) [55+/-8 mL], n = 5); group B (high mPaw [21.2+/-0.2 cm H2O]/small V(T) [18+/-1 mL], n = 5); and group C (high mPaw [21.8+/-0.5 cm H2O]/large V(T) [53+/-5 mL], n = 5). MEASUREMENTS AND MAIN RESULTS: Continuous weight gain (edema formation), change in ultrafiltration coefficient (deltaKf, vascular permeability index), and histology (lung hemorrhage) were examined. In group A, deltaKf (0.08+/-0.08 g/min/cm H2O/100 g) was less than in group B (0.28+/-0.19 g/min/cm H2O/100 g) or group C (0.41+/-0.29 g/min/cm H2O/100 g) (p = .05). Group A experienced significantly less hemorrhage (histologic score, 5.4+/-2.2) than groups B (10.3+/-2.1) and C (11.1+/-3.0) (p < .05). A similar trend was observed for weight gain. In contrast to tidal excursion, mPaw was found to be a significant factor for lung hemorrhage and increased Kf (two-way analysis of variance; p < .05). Weight gain (r2 = .54, p = .04) and lung hemorrhage (r2 = .65, p = .01) correlated with the mean pulmonary artery pressure changes that resulted from the implementation of the ventilatory strategies. The difference between the changes in mPaw and mean pulmonary artery pressure linearly predicted deltaKf (p = .005 and .05, respectively, r2 = 0.73). CONCLUSIONS: Under these experimental conditions, mPaw contributes more than tidal excursion to lung hemorrhage and permeability alterations induced by mechanical ventilation.     

Partial liquid ventilation and positive end-expiratory pressure reduce ventilator-induced lung injury in an ovine model of acute respiratory failure

OBJECTIVE: To examine the isolated and combined effects of positive end-expiratory pressure (PEEP) and partial liquid ventilation (PLV) on the development of ventilator-induced lung injury in an ovine model. DESIGN: Prospective controlled animal study. SETTING: University-based cardiovascular animal physiology laboratory. SUBJECTS: Thirty-eight anesthetized supine sheep weighing 22.3 +/- 2.2 kg. INTERVENTIONS: Animals were ventilated for 6 hrs (respiratory rate, 15; FIO2, 1.0, inspiratory/expiratory ratio, 1:1) with one of five pressure-controlled strategies, expressed as peak inspiratory pressure (PIP)/PEEP: low-PIP, 25/5 cm H2O (n = 8); high-PIP, 50/5 cm H2O (n = 8); high-PIP-PLV, 50/5 cm H2O-PLV (n = 8); high-PEEP, 50/20 cm H2O (n = 7); and high-PEEP-PLV, 50/20 cm H2O-PLV (n = 7). MEASUREMENTS AND MAIN RESULTS: Compared with the low-PIP control, high-PIP ventilation increased airleak, shunt, histologic evidence of lung injury, neutrophil infiltrates, and wet lung weight. Maintaining PEEP at 20 cm H2O or adding PLV reduced the development of physiologic shunt and dependent histologic injury indexes. Neither higher PEEP nor PLV reduced the high incidence of barotrauma observed in high-PIP animals. CONCLUSIONS: We conclude that application of PLV or PEEP at 20 cm H2O may improve gas exchange and afford lung protection from ventilator-induced lung injury during high-pressure mechanical ventilation in this model.     

Partial liquid ventilation in severely surfactant-depleted, spontaneously breathing rabbits supported by proportional assist ventilation

OBJECTIVE: We hypothesized that partial liquid ventilation (PLV) would improve oxygenation in nonparalyzed, surfactant-deficient rabbits breathing spontaneously while supported by proportional assist ventilation (PAV). This ventilation mode compensates for low pulmonary compliance and high resistance and thereby facilitates spontaneous breathing. DESIGN: Randomized trial. SETTING: University animal research facility. SUBJECTS: Twenty-six anesthetized New Zealand white rabbits weighing 2592 +/- 237g (mean +/- sd). INTERVENTIONS: After pulmonary lavage (target Pao2 <100 mm Hg on mechanical ventilation with 6 cm H2O of positive end-expiratory pressure [PEEP] and an Fio2 of 1.0), rabbits were randomized to PAV (PEEP of 8 cm H2O) with or without PLV. PLV rabbits received 25 mL/kg of perfluorocarbon by intratracheal infusion (1 mL/kg/min). Pao2, Paco2, tidal volume, respiratory rate, minute ventilation, mean airway pressure, arterial blood pressure, heart rate, pulmonary compliance, and airway resistance were measured. Evaporated perfluorocarbon was refilled every 30 mins in PLV animals. After 5 hrs, animals were killed and lungs were removed. Lung injury was evaluated using a histologic score. MAIN RESULTS: Pao2 and compliance were significantly higher in PLV rabbits compared with controls (p <.05, analysis of variance for repeated measures). All other parameters were similar in both groups. CONCLUSIONS: PLV improved oxygenation and pulmonary compliance in spontaneously breathing, severely surfactant-depleted rabbits supported by PAV. The severity of lung injury by histology was unaffected.     

Injurious ventilatory strategies increase cytokines and c-fos m-RNA expression in an isolated rat lung model.

We examined the effect of ventilation strategy on lung inflammatory mediators in the presence and absence of a preexisting inflammatory stimulus. 55 Sprague-Dawley rats were randomized to either intravenous saline or lipopolysaccharide (LPS). After 50 min of spontaneous respiration, the lungs were excised and randomized to 2 h of ventilation with one of four strategies: (a) control (C), tidal volume (Vt) = 7 cc/kg, positive end expiratory pressure (PEEP) = 3 cm H2O; (b) moderate volume, high PEEP (MVHP), Vt = 15 cc/kg; PEEP = 10 cm H2O; (c) moderate volume, zero PEEP (MVZP), Vt = 15 cc/kg, PEEP = 0; or (d) high volume, zero PEEP (HVZP), Vt = 40 cc/kg, PEEP = 0. Ventilation with zero PEEP (MVZP, HVZP) resulted in significant reductions in lung compliance. Lung lavage levels of TNFalpha, IL-1beta, IL-6, IL-10, MIP-2, and IFNgamma were measured by ELISA. Zero PEEP in combination with high volume ventilation (HVZP) had a synergistic effect on cytokine levels (e.g., 56-fold increase of TNFalpha versus controls). Identical end inspiratory lung distention with PEEP (MVHP) resulted in only a three-fold increase in TNFalpha, whereas MVZP produced a six-fold increase in lavage TNFalpha. Northern blot analysis revealed a similar pattern (C, MVHP < MVZP < HVZP) for induction of c-fos mRNA. These data support the concept that mechanical ventilation can have a significant influence on the inflammatory/anti-inflammatory milieu of the lung, and thus may play a role in initiating or propagating a local, and possibly systemic inflammatory response.     

The effect of tumor necrosis factor-alpha on microvascular permeability in an isolated,perfused lung

This study examines the hypotheses that TNF-alpha causes a dose-dependent increase in the microvascular permeability of ex vivo buffer perfused lungs that is quantitatively similar to that caused by lipopolysaccharide (LPS) or thromboxane A2 (TxA2). We also postulated that TNF-alpha potentiates the effect of interleukin-1beta (IL-1beta) or TxA2 receptor activation on pulmonary microvascular permeability. Lungs harvested from Wistar rats were perfused ex vivo with Krebs-Henseleit buffer containing 0, 10, 100, or 1000 ng/mL recombinant rat TNF-alpha. Twenty minutes later pulmonary microvascular permeability was determined by measuring the capillary filtration coefficient (Kf) using a gravimetric technique. The effect of TNF-alpha (100 ng/mL) on pulmonary Kf was compared with that of lungs exposed to LPS (400 microg/mL; E. coli 0111:B4) or a TxA2 receptor agonist (U-46619; 7 x 10(-8)). In other experiments, perfused lungs were exposed to TNF-alpha plus IL-1beta (1 ng/mL) or TNF-alpha plus U-46619 after which Kf was measured. Exposure of ex vivo buffer perfused lungs to 10-1000 ng/mL TNF-alpha had no effect on Kf whereas LPS and U-46619 was associated with a two- and six-fold increase in Kf, respectively (P < 0.05). The Kf of lungs exposed to TNF-alpha plus IL-1 was similar to that of lungs exposed to TNF-alpha alone. Lastly, the Kf of lungs exposed to TNF-alpha plus U-46619 was not different than that of lungs exposed to U-46619 alone. In conclusion, TNF-alpha at least when administered for a relatively brief period of time does not affect microvascular permeability in an isolated, buffer-perfused lung model.     

A comparison of intratracheal pulmonary ventilation to conventional ventilation in a surfactant deficient animal model

OBJECTIVE: To compare intratracheal pulmonary ventilation (ITPV) with conventional ventilation in a rabbit model of surfactant deficiency. DESIGN: A prospective randomized animal study. SETTING: The Children's National Medical Center Research Animal Facility in Washington, DC. SUBJECTS: Adult male New Zealand white rabbits (n = 20), weighing 1.4-4.2 kg. INTERVENTIONS: After anesthesia and catheter placement, rabbits were tracheotomized, paralyzed, and placed on the conventional ventilator. We determined pulmonary functions at baseline. We washed surfactant out of the lungs by using serial bronchoalveolar lavages. Pulmonary function studies were determined after completion of the bronchoalveolar lavages and were used as an indication of severity of lung injury. Animals were randomized into two groups: We placed ten animals on ITPV, using the ITPV reverse thruster catheter designed by Kolobow and a prototype ITPV ventilator designed at Children's National Medical Center; we placed ten animals on conventional ventilation using the Sechrist iv-100 ventilator. Arterial blood gases were drawn every 15 mins, and the ventilator settings were adjusted to the minimal level that would maintain arterial blood gases in the following ranges: pH 7.35-7.45, PaCO2 30-40 torr (3.995.33 kPa), PaO2 50-70 torr (6.66-9.33 kPa). Animals were ventilated with the randomized ventilation techniques for 4 hrs. MEASUREMENTS AND MAIN RESULTS: Peak inspiratory pressure, mean airway pressure, and positive end-expiratory pressure were measured at the distal end of the endotracheal tube. We recorded these variables plus respiratory rate at baseline and every 30 mins for a total of 4 hrs of ventilation. Lung compliance did not differ between groups at the postlavage study period (ITPV, 0.56+/-0.13 mL/cm H2O/kg; conventional 0.49+/-0.15 mL/cm H2O/kg). At the end of the 4 hr study period, peak inspiratory pressure (ITPV, 26.2+/-4.6 cm H2O; conventional, 32.4+/-5.04 cm H2O, p = .007) and positive end-expiratory pressure (ITPV, 3.9+/-1.96 cm H2O; conventional, 6.3+/-1.42 cm H2O, p = .005) were lower in the ITPV ventilation group. Peak inspiratory pressure was significantly lower in the ITPV group by 2 hrs into the study. CONCLUSION: In this model of surfactant deficiency lung injury, ventilation and oxygenation were achieved at significantly lower ventilator settings using ITPV compared with conventional ventilation. Long-term studies are needed to determine whether this reduction in ventilation is maintained, and if so, if lung injury is reduced.     

Pneumothorax and pneumomediastinum during pediatric mechanical ventilation.

The incidence of pulmonary barotrauma during mechanical ventilation in children beyond the neonatal age group was studied in two groups of patients. In the first group, 179 cases of pediatric mechanical ventilation for over 12 hours were retrospectively analyzed for the occurrence of pneumothorax and pneumomediastrinum. Eleven percent (6 of 57) of young infants (0--6 months) without hyaline membrane disease and 3% (4 of 122) of older infants and children (over 6 months) developed these complications. Pulmonary barotrauma in young infants occurred only after cardiothoracic surgery and involved the same site as the intraoperative repair in all cases. Pulmonary barotrauma in older infants and children occurred in patients with severe respiratory disease requiring high peak airway pressures, PEEP, and respiratory rates. In the second group, the incidence of pulmonary barotrauma during ventilation with PEEP greater than or equal to 15 cm H2O was analyzed in 14 patients including 4 patients from the previous group. Overall, 64% (9 of 14) of this group developed pulmonary barotrauma and 43% (6 of 14) developed pneumothorax. Of 9 patients receiving PEEP greater than or equal to 15 cm H2O for longer than 24 hours, 6 developed pulmonary barotrauma after the first 24 hours. The incidence of pneumothorax and pneumomediastinum in ventilated infants without hyaline membrane disease and children is comparable to adult series.     

Effects of partial liquid ventilation on regional pulmonary blood flow distribution of isolated rabbit lungs

OBJECTIVE: Partial liquid ventilation with perfluorocarbons may increase alveolar hydrostatic transmural pressure and may result in a redistribution of pulmonary blood flow from dependent to nondependent lung regions. To test this hypothesis under controlled study conditions, we determined intrapulmonary blood flow distributions during gas and perfluorocarbon ventilation in isolated rabbit lungs. DESIGN: Controlled animal study with an ex vivo isolated lung preparation. SETTING: Research laboratory for Experimental Anesthesiology at the Heinrich-Heine-University of Düsseldorf. SUBJECTS: New Zealand White rabbits. INTERVENTIONS: The lungs were perfused with autologous blood at constant flow (150 mL/min) and ventilated with 5% C(O2) in air (positive end-expiratory pressure, 2 cm H2O; tidal volume, 10 mL/kg body weight; respiratory rate, 30 breaths/ min) without and with perfluorocarbon administered intratracheally (15 mL/kg). MEASUREMENTS AND MAIN RESULTS: Regional lung perfusion was measured with colored microspheres in apical, central, peripheral, and basal samples before and after bronchial instillation of perfluorocarbons. Compared with gas ventilation, intrapulmonary blood flow during perfluorocarbon ventilation was higher in apical samples (49.4+/-8.6 mL/min/g vs. 38.3+/-6.8 mL/min/g dry weight; p = .03) and lower in basal samples (22.2+/-5.1 mL/min/g vs. 39.9+/-8.2 mL/min/g; p = .04). CONCLUSIONS: Our findings suggest that during partial liquid ventilation, intrapulmonary blood flow is redistributed toward less-dependent lung regions. (Crit Care Med 2000; 28:1522-1525) KEY WORDS: partial liquid ventilation; perfluorocarbons; isolated rabbit lungs; pulmonary circulation; regional blood-flow distribution; colored microspheres     

Intratracheal pulmonary ventilation in a rabbit lung injury model: continuous airway pressure monitoring and gas exchange efficacy

OBJECTIVES: To compare carinal pressures vs. proximal airway pressures, and gas exchange efficacy with a constant minute volume, in lung-injured rabbits during conventional mechanical ventilation (CMV) and intratracheal pulmonary ventilation (ITPV); and to evaluate performance of a prototype ITPV gas delivery and continuous airway pressure monitoring system. DESIGN: Prospective controlled study. SETTING: Animal research laboratory at a teaching hospital. SUBJECTS: Sixteen adult female rabbits. INTERVENTIONS: Anesthetized rabbits were tracheostomized with a multilumen endotracheal tube. Anesthesia and muscle relaxation were maintained continuously throughout the study. Proximal airway pressures and carinal pressures were recorded continuously. The injection port of the multilumen endotracheal tube was used for the carinal pressure monitoring. To prevent obstruction of the port, it was flushed with oxygen at a rate of 11 mL/min. CMV was initiated with a pressure-limited, time-cycled ventilator set at an FiO2 of 1.0 and at a flow of 1.0 L/kg/min. The pressure limit of the ventilator was effectively disabled. A normal baseline for arterial blood gases was achieved by adjusting the inspiratory/expiratory time ratios. ITPV was established using a flow of 1.0 L/kg/min through a reverse thrust catheter, at the same baseline and inspiratory/expiratory ratio. Carinal positive end-expiratory pressure was maintained at a constant value of 2 cm H2O by adjusting the expiratory resistance of the ventilator circuit Lung injury was achieved over a 30-min period by three normal saline lavages of 5 mL/kg each. After lung injury, all animals were consecutively ventilated for 1 hr with CMV, for 1 hr with ITPV, and again for 1 hr with CMV. Six rabbits were ventilated at 30 breaths/min (group 1), and ten rabbits were ventilated at 80 breaths/min (group 2). Four rabbits in group 2 were subjected, 1 hr after return to CMV from ITPV, to another session of ITPV, with positive end-expiratory pressure gradually being increased to 4, 6, and 8 cm H2O for 15 mins each. RESULTS: No significant differences were observed in carinal peak inspiratory pressure between CMV and ITPV modes, at both low and high frequencies of breathing, indicating that the inspired tidal volume remained constant during both modes of ventilation. Significant gradients were noted between proximal airway and carinal peak inspiratory pressure during ITPV but not during CMV. Initiation of ITPV, at a flow of 1.0 L/kg/min, required an increase in the ventilator expiratory resistance to maintain a constant level of positive end-expiratory pressure (2 cm H2O) as measured at the carina. During ITPV, the PaCO2 was significantly reduced by 20% at 30 breaths/min (p < .05) and by 22% at 90 breaths/min (p < .01), compared with CMV. Arterial oxygenation was significantly enhanced with a positive end-expiratory pressure of 6 and 8 cm H2O (p < .05 and .001, respectively), compared with a positive end-expiratory pressure of 2 cm H2O during ITPV. All components of the new prototype gas delivery and airway pressure monitoring system functioned without failure, at least for 3 hrs of the CMV, ITPV, and CMV trials. CONCLUSIONS: ITPV in saline-lavaged, lung-injured rabbits at breathing frequencies of 30 and 80 breaths/min, compared with CMV at the same minute ventilation, can improve CO2 exchange. During ITPV, significant pressure gradients can develop between carinal and proximal airway pressures. Continuous carinal pressure monitoring is therefore necessary for the safe clinical application of ITPV. Reliable carinal pressure monitoring can be achieved by adding a small bias flow through the carinal pressure monitoring port. Although ITPV can remove CO2 from injured lungs efficiently, simultaneous addition of positive end-expiratory pressure can further improve arterial oxygenation.     

吸入沙丁胺醇对呼吸衰竭患者容积标限压力控制通气时通气参数的影响

目的　探讨在容积标限压力控制 (VTPC)通气时吸入支气管扩张剂沙丁胺醇后对机械通气参数的影响。方法　 10例平均年龄为 (6 8± 5 )岁的呼吸衰竭患者均接受气管插管与机械通气支持治疗 ;采用Newport e5 0 0型呼吸机 ,并实施定容型通气 (VCV) 30 min,潮气量 (VT)为 8～ 10 ml/ kg;测定气道阻力 (Raw)和静态顺应性 (Cst)以及通气参数的变化 ,包括气道峰压 (PIP)、平台压 (Pplat)、充气时间 (Tinflate)、吸气峰流速(PIF)、呼气峰流速 (PEF)和平均吸气流速 (VT/ Tinflate)。随后转为 VTPC通气 30 m in,并同样记录上述参数。通过同轴吸入装置吸入沙丁胺醇 6 0 0 μg后重复 VCV和 VTPC通气 ,并记录上述通气参数。结果　 10例患者的 Cst为 (38.4± 2 .7) ml/ cm H2 O,Raw为 (2 0 .1± 2 .0 ) cm H2 O· L- 1 · s- 1 。VTPC时 PIP和 VT/ Tinflate较 VCV时显著降低 (P均 <0 .0 5 ) ,PIF则显著增高 ,两种通气时的 Pplat无显著性差异 ,分别为 (2 2 .1± 0 .9) cm H2 O和(2 3.0± 1.2 ) cm H2 O(P>0 .0 5 )。吸入沙丁胺醇后患者的 Raw均显著降低 ,而 Cst无明显变化 ,VCV时的 PIP有所降低 ,但 Pplat无变化 ;VTPC时的 PIP和 Pplat与吸入前比较无明显改变 ,但 PIF和 PEF出现显著增高 ,Tinflate则相应缩短 (P均 <0 .0 5