Reduced activation of immunomodulatory transcription factors during positive end-expiratory pressure adjustment based on volume-dependent compliance in isolated perfused rabbit lungs.

BACKGROUND: Repeated alveolar collapse and cyclic alveolar overdistension with associated activation of inflammatory signalling cascades contribute to ventilator-induced lung injury (VILI). The appropriate positive end-expiratory pressure (PEEP) which prevents or ameliorates VILI is unknown. In the isolated perfused lung, repeated adjustments of PEEP based on the continuously analysed intratidal compliance-volume curve have previously been shown to result in full end-expiratory alveolar recruitment and low risk of cyclic alveolar overdistension. Accordingly, we tested the hypothesis that such ventilatory management reduces intrapulmonary activation of the immunomodulatory transcription factors nuclear factor kappaB (NF-kappaB), activator protein 1 (AP-1) and cAMP-responsive element binding protein (CREB) which induce the expression of various chemokines and cytokines. METHODS: Isolated perfused rabbit lungs were randomly allocated to one of three groups: zero end-expiratory pressure (ZEEP) to induce repeated alveolar collapse (n=6), high PEEP to induce cyclic alveolar overdistension (n=6) and repeated PEEP adjustments based on intratidal compliance-volume curve analysis by the slice method to minimize repeated alveolar collapse and overdistension (n=9). All lungs were ventilated with a tidal volume of 6 ml kg(-1) bodyweight for 120 min. Thereafter, activation of transcription factors NF-kappaB, AP-1 and CREB in lung tissue was analysed by electrophoretic mobility shift assay. RESULTS: High PEEP was associated with the highest activation of NF-kappaB and AP-1 and repeated PEEP adjustments with the lowest activation when compared with the other two study groups (P<0.001). In contrast, activation of CREB did not differ between groups. Activated NF-kappaB and AP-1 protein complexes consisted mainly of the transactivators p50/p65 and c-Fos/Jun, respectively. CONCLUSIONS: In isolated perfused rabbit lungs, repeated adjustments of PEEP based on the continuously analysed intratidal compliance-volume curve were associated with less activation of early steps of inflammatory signalling cascades than ventilation with ZEEP or high PEEP.

[10 years experience with extracorporeal membrane oxygenation]. / Zehn Jahre Erfahrung mit extrakorporaler Membranoxygenierung (ECMO).

OBJECTIVE: Extracorporeal membrane oxygenation (ECMO) is a supportive therapy used for severe acute respiratory distress syndrome (ARDS). We present outcome, clinical parameters, and complications in a cohort of 245 ARDS patients of whom 62 were treated with ECMO. METHODS: Data of all ARDS patients were prospectively collected between 1991 and 1999. Outcome and clinical parameters of patients treated with and without ECMO were evaluated. RESULTS: Hundred-thirty-eight patients were referred from other hospitals, 107 were primarily located in our hospital. About one fourth of these patients was treated with ECMO. The survival rate was 55% in ECMO patients and 61% in non-ECMO patients. ECMO resulted in very few complications, one of them was fatal. No parameter before or during ECMO could be used to predict the individual prognosis. CONCLUSION: ECMO is a therapeutic option for patients with severe ARDS, likely to increase survival. However, a randomized controlled study proving its benefit is still awaited. Until the development of a causal or otherwise superior therapy ECMO should be used in selected patients.

Volume-dependent compliance and ventilation-perfusion mismatch in surfactant-depleted isolated rabbit lungs.

OBJECTIVE: Volume-dependent alterations of lung compliance are usually studied over a very large volume range. However, the course of compliance within the comparably small tidal volume (intratidal compliance-volume curve) may also provide relevant information about the impact of mechanical ventilation on pulmonary gas exchange. Consequently, we determined the association of the distribution of ventilation and perfusion with the intratidal compliance-volume curve after modification of positive end-expiratory pressure (PEEP). DESIGN: Repeated measurements in randomized order. SETTING: An animal laboratory. SUBJECTS: Isolated perfused rabbit lungs (n = 14). INTERVENTIONS: Surfactant was removed by bronchoalveolar lavage. The lungs were ventilated thereafter with a constant tidal volume (10 mL/kg body weight). Five levels of PEEP (0-4 cm H2O) were applied in random order for 20 mins each. MEASUREMENTS AND MAIN RESULTS: The intratidal compliance-volume curve was determined with the slice method for each PEEP level. Concurrently, pulmonary gas exchange was assessed by the multiple inert gas elimination technique. At a PEEP of 0-1 cm H2O, the intratidal compliance-volume curve was formed a bow with downward concavity. At a PEEP of 2 cm H2O, concavity was minimal or compliance was almost constant, whereas higher PEEP levels (3-4 cm H2O) resulted in a decrease of compliance within tidal inflation. Pulmonary gas exchange did not differ between PEEP levels of of 0, 1, and 2 cm H2O. Pulmonary shunt was lowest and perfusion of alveoli with a normal ventilation-perfusion was highest at a PEEP of 3-4 cm H2O. Deadspace ventilation did not change significantly but tended to increase with PEEP. CONCLUSIONS: An increase of compliance at the very beginning of tidal inflation was associated with impaired pulmonary gas exchange, indicating insufficient alveolar recruitment by the PEEP level. Consequently, the lowest PEEP level preventing alveolar atelectasis could be detected by analyzing the course of compliance within tidal volume without the need for total lung inflation.

Ventilation-perfusion mismatch after lung ischemia-reperfusion. Protective effect of nitric oxide.

Lung ischemia-reperfusion provokes pulmonary hypertension and increased microvascular permeability with subsequent edema formation and hypoxemia. We exposed buffer-perfused rabbit lungs to 120 and 180 min of warm ischemia. After reperfusion, gas exchange disturbances were analyzed by the multiple inert gas elimination technique (MIGET). Additionally, ischemic lungs were treated with different doses of inhaled nitric oxide (NO) throughout reperfusion. Reperfusion provoked a transient pulmonary artery pressure elevation, followed by progressive pulmonary edema formation. After 120 min of ischemia, severe ventilation-perfusion (V A/Q) mismatch developed within 15 min of reperfusion, with the appearance of low V A/Q areas and marked broadening of both perfusion and ventilation distribution in the midrange V A/Q regions. In parallel, shunt flow increased from less than 2% to approximately 17%. Inhalation of NO suppressed the pressor response, edema formation, as well as V A/Q mismatch and shunt flow. Concentrations of 10 and 50 ppm NO were equipotent, surpassing the efficacy of 1 or 250 ppm NO. Inhalation of NO, however, did not protect from the overwhelming gas exchange and fluid balance disturbances provoked by 180 min ischemia. In conclusion, severe abnormalities in gas exchange occurred rapidly upon reperfusion of ischemic lungs. Prophylactic NO inhalation may be considered for maintenance of gas exchange in settings of ischemia-reperfusion including lung transplantation.

Vascular distension and continued ventilation are protective in lung ischemia/reperfusion.

Biophysical factors have been implicated in the development of pulmonary ischemia-reperfusion injury. In isolated rabbit lungs, the impact of vascular and alveolar distension, with and without alveolar oxygen supply, was investigated. With interruption of both perfusion (zero intravascular pressure) and ventilation, reperfusion after 120 min of warm ischemia resulted in transient pulmonary hypertension, with largely unchanged microvascular pressures, followed by a dramatic leakage response with approximately 10-fold increased capillary filtration coefficients (Kfc) and severe edema. Maintenance of vascular distension during ischemia (intravascular pressure of approximately 2 to 3 mm Hg) reduced the hypertension and fully suppressed the leakage. Employing ischemic periods of 180 and 240 min, ventilation of the lungs with 21 or 100% oxygen > ventilation with nitrogen during perfusion stop, but not static anoxic inflation, further enhanced the protective effect of vascular distension. At optimal biophysical support (vascular distension and ongoing normoxic ventilation), even 240 min of warm ischemia was tolerated with only moderate Kfc increase. We conclude that biophysical factors exert marked influence on pulmonary ischemia-reperfusion injury. Maintenance of vascular distension possesses strong protective potency, further enhanced by continued ventilation and alveolar oxygen supply during ischemia. These results may have important implications for organ preservation in lung transplantation.

Periapical status, quality of root canal fillings and estimated endodontic treatment needs in an urban German population.

The objective of this study was to determine the periapical status and the quality of root canal fillings and to estimate the endodontic treatment needs in a German population. Clinical and radiographic data and the operative procedures performed were evaluated on 323 patients coming to a dental surgery in Stuttgart, Germany, in 1993. In 182 individuals at least one tooth exhibited a root canal filling, a necrotic pulp or an irreversible pulpitis. Out of the 7897 teeth examined, 215 (2.7%) had a root canal treatment (category A), 122 being non-endodontically treated (1.5%) did not respond to the sensitivity test (category B) and 53 (0.7%) were diagnosed as having irreversible inflamed pulp tissue (category C). The prevalence of teeth associated with radiographic signs of periapical pathosis was 61% in the group of root canal filled teeth and 88% in the group of pulpless and non-endodontically treated teeth. Using the level and the density of the root canal filling as criteria for evaluating the technical standard, only 14% of the endodontic treatments of non-apicectomized teeth were qualified as adequate. The minimal endodontic treatment need is 2.3% related to all examined teeth when the root canal filled teeth with clinical symptoms of periapical periodontitis (category A) and those of categories B and C are included. The real endodontic treatment need is suggested to be larger when considering that the technical quality of the obturation is poor in most symptomless endodontically treated teeth associated with a periapical lesion. In the case of retreatment of these teeth, the endodontic treatment need would then be calculated at 3.7%.