In infants with congenital diaphragmatic hernia (CDH), abnormalities of the pulmonary arteries are present consisting of increased medial wall thickness and decreased external diameter. This forms the morphological substrate for persistent pulmonary hypertension, one of the leading causes of the high mortality in these patients. To elucidate the significance of these abnormalities, experimental models are required that mimic as close as possible the human situation. In our rat model we are able to study the hypoplastic CDH lungs extensively. In this study we performed a histological evaluation of the pulmonary arterial bed in the control group and the nitrofen-treated group in which the latter was divided into two subgroups, CDH and normal diaphragm. We examined the newborn rats after perfusion of the pulmonary arteries with barium gelatine and subsequent fixation. At the level of the respiratory bronchioles significant differences in the vessels were found consisting of decreased external diameter and increased wall thickness as percentage of the external thickness in CDH lungs compared with controls. Abnormal muscularization of the peripheral branches of the CDH pulmonary arteries was also found. We concluded that the rat model strongly resembles the human situation concerning the arterial bed in the lungs.

Animals↗

PubMed1992

Comparison of ketorolac and morphine for postoperative pain after major surgery.

This study was designed to determine the relative analgesic efficacy and safety of single intramuscular injections of ketorolac (10 mg or 30 mg) and morphine (10 mg) in patients of either sex with moderate to severe pain after major surgery. In a single-dose, randomised, double-blind study of parallel design, pain was assessed immediately before injection of test medication and at regular intervals for 8 h thereafter. One hundred and seventeen patients (109 undergoing cardiac surgery; 8 lung surgery) were randomized to one of the three treatment groups. Pain intensity was assessed using a 5-point verbal scale before administration of study drugs. Postadministration, at 30 min and hourly for 8 h, pain intensity and pain relief were assessed, again using the 5-point verbal scale. Additionally, as a measure of analgesia, forced expiratory volume (FEV1) was obtained in all patients. Vital signs including blood pressure, pulse, temperature, respiratory rate and blood gases (PaCO2) were recorded prior to and after study medication. Based on hourly pain intensity differences and hourly pain relief observations, ketorolac 10 mg was generally more effective than morphine 10 mg, and ketorolac 30 mg was generally more effective than ketorolac 10 mg. The results of this study show that ketorolac is an effective and safe (with regard to arterial pressure, blood gases and lung function) analgesic for relief of postoperative pain after major surgery in stable patients. No clinically significant adverse effects occurred during the study. One cannot exclude an influence on patients with organ system dysfunction or on parameters not measured in this study.

Adult↗

PubMed1992

Integrity of the alveolar-capillary barrier and alveolar surfactant system in smokers.

BACKGROUND: The permeability of the alveolar-capillary barrier to technetium-99m labelled diethylenetriamine pentaacetate (99mTc DTPA) is known to be greatly increased in smokers, but the underlying mechanism is poorly understood. Abnormal permeability of the alveolar epithelium as well as impaired surfactant function has been suggested. The purpose of this study was to examine transudation of urea and albumin into the alveoli and alveolar surfactant function in smokers and non-smokers and to relate these variables to the rate of alveolar-capillary transfer of 99mTc DTPA. METHODS: Standardised bronchoalveolar lavage was performed and the yield of urea and albumin measured in the lavage fluid. The integrity of the alveolar surfactant system was assessed by measurement of the surface activity and of the yield of phospholipids in alveolar lavage fluid. RESULTS: The mean decay constant for the pulmonary clearance of 99mTc DTPA was 0.028/min in the smokers and 0.009/min in the non-smokers. The recovery of albumin and urea in alveolar lavage fluid was very similar in the two groups. The surface activity of alveolar lavage fluid was lower in smokers than in non-smokers (minimum surface tension 37.9 versus 28.6 mN/m) and the yield of phospholipids was reduced (2.08 versus 3.86 mg). The rate constant for the pulmonary clearance of 99mTc DTPA correlated with the yield of phospholipids at bronchoalveolar lavage. CONCLUSIONS: The study shows that increased alveolar-capillary transfer of 99mTc DTPA in smokers is not accompanied by increased transudation of small or large molecules into the alveoli. The findings support the hypothesis that increased clearance of 99mTc DTPA in smokers is related to surfactant dysfunction.

Adult↗

PubMed1992

Clearance of 99mTc-DTPA and experimentally increased alveolar surfactant content.

We measured clearance of 99mTc-labeled diethylenetriamine pentaacetic acid (99mTc-DTPA) in rabbits with experimentally increased alveolar surfactant content. In one group of animals, surfactant production was increased by treatment with ambroxol, and another group of animals was treated with tracheal instillation of natural surfactant. A group of untreated control animals and animals treated with instillation of saline were also studied. Clearance was measured during standard conditions of mechanical ventilation and during ventilation with large tidal volumes. In ambroxol- and surfactant-treated groups, clearance rate was reduced compared with untreated control animals. In contrast, clearance rate increased after saline instillation. The differences were observed at both modes of ventilation. The findings indicate that the pulmonary surfactant system is a rate-limiting factor for the clearance of 99mTc-DTPA and that the volume dependence of clearance is not explained by stretching of the alveolar wall only.

Ambroxol↗

PubMed1992

Functional residual capacity and ventilation homogeneity in mechanically ventilated small neonates.

A modification of a computerized tracer gas (SF6) washout method was designed for serial measurements of functional residual capacity (FRC) and ventilation homogeneity in mechanically ventilated very-low-birth-weight infants with tidal volumes down to 4 ml. The method, which can be used regardless of the inspired O2 concentration, gave accurate and reproducible results in a lung model and good agreement compared with He dilution in rabbits. FRC was measured during 2-4 cmH2O of positive end-expiratory pressure (PEEP) in 15 neonates (700-1,950 g), most of them with mild-to-moderate respiratory distress syndrome. FRC increased with body weight and decreased (P less than 0.05) with increasing O2 requirement. Change to zero end-expiratory pressure caused an immediate decrease in FRC by 29% (P less than 0.01) and gave FRC (ml) = -1.4 + 17 x weight (kg) (r = 0.83). Five minutes after PEEP was discontinued (n = 12), FRC had decreased by a further 16% (P less than 0.01). The washout curves indicated a near-normal ventilation homogeneity not related to changes in PEEP. This was interpreted as evidence against the presence of large volumes of trapped alveolar gas.

Body Weight↗

PubMed1992

Oral immunization with polyvalent bacterial lysate and infection with Streptococcus pneumoniae: influence on interferon-gamma and PMN elastase concentrations in murine bronchoalveolar lavage fluid.

We recently demonstrated that oral immunization with a polyvalent bacterial lysate (Paspat oral) significantly reduces mortality rates in mice, infected with Streptococcus pneumoniae or influenza A virus. In this study it is demonstrated that oral immunization with the same bacterial lysate reduces the intrapulmonary inflammatory reaction to infection with S. pneumoniae, assessed by measurement of PMN elastase in bronchoalveolar lavage fluid. Furthermore, it is demonstrated that oral immunization with Paspat oral increases intrapulmonary IFN-gamma concentrations.

Administration, Oral↗

PubMed1992

Surfactant replacement therapy improves pulmonary mechanics in end-stage influenza A pneumonia in mice.

Surfactant replacement therapy may be a promising approach for treatment of respiratory failure caused by viral pneumonia. This study in mice demonstrates that during the development of lethal influenza A pneumonia, thorax-lung compliance (Ctl/kg) and lung volume at 5 cm H2O PEEP (V5/kg) significantly decrease (28 and 54%, respectively), whereas lung water content significantly increases (25%). Surfactant replacement therapy during the end stage of pneumonia significantly increases Ctl/kg (31%) and V5/kg (21%). Instillation of the vehicle for surfactant in control animals does not significantly affect Ctl/kg (5% decrease), but it significantly decreases V5/kg (25% decrease). Further, a new method for postmortem measurement of lung volumes in small laboratory animals based on Archimedes' principle is presented.

Animals↗

PubMed1992

Natural surfactant instilled in premature lambs increases lung volume and improves ventilation homogeneity within five minutes.

The immediate effects on lung volume, ventilation homogeneity, and lung mechanics of tracheal instillation of surfactant were studied in premature lambs, gestational age 120-122 d, with respiratory distress syndrome. Six lambs received surfactant by tracheal instillation 25 min after delivery by cesarean section; five received only vehicle and served as controls. The lambs were studied for 60 min thereafter. Functional residual capacity was measured with a computerized tracer gas washin-washout technique using sulfur hexafluoride as tracer gas. A measure of ventilation inhomogeneity (pulmonary clearance delay) was also calculated from the washout curves. Pressure-volume curves were studied with an interrupter technique during deflation of the lungs from an airway pressure of 30 cm H2O. In the surfactant group, arterial oxygenation and ventilation homogeneity improved within 5 min of giving surfactant; major increases in functional residual capacity, vital capacity, and compliance occurred within 5 to 20 min and were followed by gradual further improvements. The pressure-volume curve thus increased in amplitude and became steeper, but the lung volumes at various inflation pressures, and compliance, remained constant when expressed as fractions of total lung capacity volume. It is concluded that an improvement in lung volume, respiratory mechanics, and ventilation homogeneity occurs very soon after surfactant instillation and that there is a phase of successive further improvement over the next hour. Although the amplitude of the pressure-volume curve varied considerably, its basic shape varied little. This suggests that opening of new distal airways by surfactant predominated over changes in the mechanics of already aerated lung regions.

Animals↗

PubMed1992

Efficacy and safety of tramadol versus morphine for moderate and severe postoperative pain with special regard to respiratory depression.

The analgesic efficacy and safety of tramadol and morphine were compared in a double-blind, randomized study of 150 female patients after gynecologic surgery. As required, patients could receive up to three intravenous doses of either 50 mg of tramadol or 5 mg of morphine within a period of 6 h. Pain intensity (verbal response score) was recorded before injection and at 0.5, 1, 2, 3, 5, and 6 h after the initial dose; at these times, pain relief was also assessed. Oxygen saturation was monitored continuously by pulse oximetry for at least 30 min after each injection. In 13.3% of the morphine group (but in none of the tramadol group) transcutaneous pulse oxygen saturation decreased to less than 86%; in 50% of these patients the decrease occurred after only the first 5 mg of morphine. Both drugs produced acceptable analgesia, and there were no clinically significant adverse events. In demonstrating the absence of clinically relevant respiratory depression with tramadol, we underline its safety for postoperative pain relief.

Adolescent↗