Katsumi Tashiro

Aerosolized and instilled surfactant therapies for acute lung injury caused by intratracheal endotoxin in rats

OBJECTIVE To compare the effects of surfactant replacement by aerosol inhalation and bolus instillation on acute lung injury caused by the intratracheal injection of endotoxin in rats. DESIGN Prospective, randomized study. SETTING University Laboratory. SUBJECTS Male Wistar rats weighing 368 +/- 31 (SD) g. INTERVENTIONS Escherichia coli endotoxin (57 +/- 20 mg/kg) was injected into the tracheas of 36 anesthetized and mechanically ventilated rats (FIO of 1.0). When the PaO2 had decreased to <200 torr (<26.7 kPa), the rats were randomly assigned to one of three groups: a control group (n=12)given no material; a bolus group (n=12) given a modified natural surfactant suspension (100 mg/kg in 2.0 mL/kg saline) by bolus instillation into the trachea; and an aerosol group (n=12) given surfactant aerosolized with an ultra-sonic nebulizer for 60 mins. MEASUREMENTS AND MAIN RESULTS Bolus instillation transiently decreased the mean blood pressure by approximately 30%. However, aerosol inhalation did not. The PaO2 values of the control group remained <90 torr (<12.0 kPa) until the end of the experiment (180 mins). In contrast, the PaO2 of the bolus group increased to 387 +/- 134 torr (51.6 +/- 17.9 kPa; p<.05 vs. other groups) 15 mins after surfactant replacement, and remained at approximately 400 torr (approximately 53.3 kPa) throughout the experiment. The PaO2 values of the aerosol group increased slowly, peaked at 240 +/- 109 torr (32.0 +/- 14.5 kPa; p<.05 vs. the control group) 60 mins after the start of surfactant replacement, and remained at approximately 200 torr (approximately 26.7 kPa). CONCLUSIONS Bolus instillation was superior to aerosol inhalation concerning maximum efficacy, the rapid onset of therapeutic effects, and the necessary dose of surfactant. However, aerosol that does not cause hypotension may be of use in the treatment of adult respiratory distress syndrome in patients with circulatory instability.

Surfactant replacement reverses respiratory failure induced by intratracheal endotoxin in rats

OBJECTIVE To evaluate the effect of surfactant replacement on respiratory failure induced by intratracheal injection of endotoxin in rats. DESIGN Prospective, randomized study. SETTING Laboratory at a large university. SUBJECTS Male Wistar rats, weighing 353 +/- 50 (SD) g. INTERVENTIONS Escherichia coli endotoxin (53 +/- 19 mg/kg) was injected into the trachea of 32 rats anesthetized with pentobarbital and mechanically ventilated with an FIO2 of 1.0. After PaO2 decreased to < 200 torr (< 26.7 kPa), the rats were assigned to three groups: a) a surfactant group (n = 16), given a modified natural surfactant suspension (100 mg/kg in 2.0 mL/kg of saline) by instillation into the airway; b) a saline control group (n = 8), given 2.0 mL/kg of saline; and c) an air control group (n = 8), given 2.0 mL/kg of air. An additional nine rats were ventilated in the same way but were not given endotoxin. MEASUREMENTS AND MAIN RESULTS Among the rats receiving endotoxin, the PaO2 of the saline and air control groups remained < 200 torr (< 26.7 kPa), while PaO2 of the surfactant group increased to 390 +/- 116 torr (52.0 +/- 15.5 kPa; p < .05 vs. the preassignment value) 15 mins after the assignment. These high levels were maintained throughout the experiment. Surfactant replacement also led to significant improvements in the PaCO2, the dynamic lung-thorax compliance, the pressure-volume recordings of the lung, and the chest roentgenograms. Histologic examination showed that the alveoli of the surfactant group were better aerated than the alveoli of the control groups. Findings in the rats not given endotoxin were almost normal, indicating that the influences of mechanical ventilation were negligible. CONCLUSION Surfactant replacement reversed respiratory failure induced by intratracheal injection of endotoxin in rats.

Modified Protocols for Surfactant Therapy in Experimental Meconium Aspiration Syndrome

In adult rats with experimental meconium aspiration syndrome, we investigated whether the therapeutic effect of exogenous surfactant was increased by addition of dextran or preceding airway lavage with diluted surfactant. Animals (n = 72) ventilated with pure oxygen were given human meconium suspension (50–75 mg kg–1) through the airways. When the PaO2 had decreased to <20 kPa (mean ± SD 12 ± 3.9 kPa), the rats were randomly allocated to ten groups (G). G 6–10 underwent lung lavage with diluted Curosurf (5 mg ml–1, 20 ml kg–1), whereas G 1–5 did not. G 1 and 6 received no additional material through the airways. G 2 and 7 received Curosurf (100 mg kg–1), and G 3 and 8 received Curosurf (100 mg kg–1) plus dextran (75 mg kg–1); G 4 and 9 received Curosurf (200 mg kg–1), and G 5 and G 10 received Curosurf (200 mg kg–1) plus dextran (75 mg kg–1). All rats in G 1 died before 180 min after randomization. In G 2, 3, 6, 7, and 8, the PaO2 transiently increased to 30–40 kPa. In G 4, 5, 9, and 10, the PaO2 remained >30 kPa for 180 min. Both airway lavage and supplementation with dextran improved the therapeutic effects of surfactant; however, a large dose (200 mg kg–1) was nevertheless required to optimize gas exchange.

Aerosolized surfactant and dextran for experimental acute respiratory distress syndrome caused by acidified milk in rats

Background:  Inhibition of pulmonary surfactant by plasma‐derived proteins is an important pathogenetic factor of acute respiratory distress syndrome (ARDS). Inhalation of aerosolized surfactant may be suitable for early treatment of ARDS. However, requirement of a high dose is a drawback. Because dextran reverses surfactant inhibition, we examined whether dextran improves the therapeutic effects of aerosolized surfactant in rats with experimental ARDS.

Experimental Models of Acute Respiratory Distress Syndrome: Clinical Relevance and Response to Surfactant Therapy

Surfactant therapy for acute respiratory distress syndrome (ARDS) has shown encouraging results in animal studies, but not always in clinical trials. Efficacy of this therapy may be limited to ARDS caused by indirect injury, but mistiming of its application in clinical trials may be responsible for the discouraging results. In addition, the therapy may not last long enough to be effective. In rats with acidified milk aspiration, the effects of aerosolized surfactant therapy followed by inhalation of aerosolized dextran (molecular weight, 40,000) last significantly longer than those of aerosolized surfactant therapy alone. This mode of surfactant therapy could lead to better results since it can be started and repeated at any time.

Modified natural and synthetically reconstituted surfactant therapies for acute lung injury caused by endotoxin in rats.

Background: Impairment of surfactant is involved in development of acute respiratory distress syndrome. To develop artificial surfactant substitute for clinical use, we prepared synthetically reconstituted surfactant (SRS) by adding porcine surfactant‐associated protein B and C (SP‐B and SP‐C) to synthetic phospholipids, and compared its effect with that of modified natural surfactant (MNS) in rats with acute lung injury caused by endotoxin.

Effects of Surfactant Replacement on Irregular Overdistension of Meconium-Injured Lungs in Rats

Background: Overdistension of the lungs is a cause of ventilator-induced lung injury. In meconium aspiration syndrome, irregular overdistension of the lungs often occurs. Objectives: We investigated whether surfactant replacement could restore the terminal airspaces in the lungs that had been distended after meconium aspiration. Methods: Meconium aspiration was induced by injecting meconium (50 mg·kg–1) into the airways of adult rats anesthetized with pentobarbital and ventilated with pressure-preset mode. The animals were further ventilated with or without surfactant replacement (100 mg·kg–1), and the sizes of the terminal airspaces were determined after fixing the lungs at an airway pressure of 10 cm H2O on deflation. Results: Approximately 75 min after aspiration (early analysis point), alveolar ducts were widened and the mean ratio of the largest terminal airspace size class (≧63,000 µm2) was 38.7% (n = 7), which was significantly higher than that of controls (6%, n = 7). Three hours after the early analysis point, the ratio increased to 50.2% (n = 7, p < 0.05), but surfactant replacement reversed the ratio to 18.8% (n = 7, p < 0.05). Conclusions: In rats with meconium aspiration, surfactant replacement restored the distended terminal airspaces of the lungs and kept the spaces from irregular overdistension.

Respiratory failure caused by massive pleural effusion in a patient with deep neck abscess.

for 2 days, but redness and swelling of the neck had developed gradually, followed by dyspnea. On admission, physical examination showed he was confused. Redness and swelling were seen on the left side of the neck, and the area around the left tonsil was extremely swollen. Blood pressure was 136/68mmHg and heart rate 125 bpm. The patient had a slight fever, temperature 37.6°C, his respiratory rate was 24 breaths per min, and stridor could be heard. SpO2 was 99% under oxygen administration (5 l·min 1) with a face mask. Blood examination showed that C-reactive protein (CRP) had increased to 47 mg·dl 1, and the white blood cell (WBC) count had increased to 12 400 ·mm 3. The examination also showed Na, 130mEq·l 1; K, 3.0 mEq·l 1; Cl, 93 mEq·l 1; blood glucose level, 422 mg·dl 1; hemoglobin A1c, 7.6%; and renal dysfunction (blood urea nitrogen [BUN], 45 mg·dl 1; creatinine [Cr], 1.5mg·dl 1). Computed tomography (CT) scan of the neck revealed an abscess extending from the peritonsillar space to the parapharyngeal and retropharyngeal space, and swelling of the area surrounding the glottis (Fig. 1), but the abscess did not extend directly into the mediastinum, and pleural effusion was not detected. Emergency surgical drainage was scheduled. In the operating room, tracheostomy was performed first, under local anesthesia because the pharynx was extremely edematous. Anesthesia was induced with thiopental (200 mg), and was maintained with sevoflurane (1.0%–1.5%) in 40% oxygen and 60% nitrous oxide under mechanical ventilation. Blood loss during the operation was 50g, and 2200 ml of acetated Ringer’s solution was administered during surgery. Bacterial examination revealed infection with a combination of aerobic ( -streptococcus) and anaerobic gram-negative rod bacteria. After surgery, PaO2 was 447 mmHg under 100% oxygen, and X-ray of the chest revealed no abnormalities. The patient was returned to a general ward. He received

The Newborn at High Risk of Brain Damage

Despite marked improvements in perinatal practice, perinatal brain injury remains one of the most common complications causing chronic handicapping conditions. Experimental advances have elucidated many of the cellular and vascular mechanisms of perinatal brain damage showing a correlation between the nature of the injury and the maturation of the brain. New diagnostic tools, such as quantitative three-dimensional magnetic resonance (MR) imaging, diffusion-weighted MR imaging and proton MR spectroscopy, are presented in this review article that allow to assess brain development, detect early brain injury and monitor effects of perinatal brain injury on subsequent brain development and brain plasticity. These techniques will guide future therapeutic interventions aimed at minimizing irreversible perinatal brain injury.

Surfactant degradation activity in bronchoalveolar lavage fluid from guinea pigs challenged with antigen

Background and objective:  Surfactant dysfunction is a characteristic of bronchial asthma, but mechanisms of dysfunction following antigen exposure are not understood. The aim of this study was to examine whether bronchoalveolar lavage fluid (BALF) has surfactant degradation activity after antigen challenge, using an animal model of asthma.