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Biomedical subjects

H Gerlach

Publications and source records attributed to H Gerlach.

At least 37 records · Page 2Linked to original sources

Response of neonatal platelets to nitric oxide in vitro.

OBJECTIVES: Several studies have demonstrated altered platelet function during nitric oxide inhalation (iNO) in adults and neonates. In vitro NO inhibits activation of fibrinogen receptor glycoprotein (GP) IIb/IIIa in a dose-dependent manner. In neonates GPIIb/IIIa response to stimulation is physiologically attenuated during the first days after birth in comparison to adults; the effects of NO on GPIIb/IIIa in neonates, however, are less established. We investigated the response of platelets from neonates, their mothers, and nonpregnant controls to the NO donor SIN-1 in vitro. DESIGN: Umbilical cord and venous (mother, controls) platelet-rich plasma was stimulated in vitro with 10 microM ADP or 0.05 U/ml thrombin in the presence or absence of 10 microM SIN-1. GPIIb/IIIa activation was determined by two-color flow cytometry. SETTING: Delivery department of an university hospital. PATIENTS AND PARTICIPANTS: Ten healthy term neonates, their mothers and nonpregnant controls. MEASUREMENTS AND RESULTS: NO significantly reduced GPIIb/IIIa activation in thrombin- and ADP-stimulated platelets in all groups (p < 0.001). Neonatal platelets were significantly hyporeactive to stimulation (p < 0.05), but the relative response to SIN-1 was similar in all three groups (70 +/- 5 %). CONCLUSIONS: The relative amount of NO-induced inhibition of GPIIb/ IIIa activation in neonates is thus similar to that of adults. However, due to the intrinsic hyporesponsiveness of neonatal platelets and NO-synergistic pharmacodynamic profiles of other drugs (e.g., prostacyclin), possible adverse effects of iNO must be considered.

Adult↗

Early detection of increased tumour necrosis factor alpha (TNFalpha) and soluble TNF receptor protein plasma levels after trauma reveals associations with the clinical course.

BACKGROUND: The inflammatory response after trauma includes tumour necrosis factor alpha (TNFalpha) as pro-inflammatory cytokine. Furthermore, both soluble TNF receptor proteins (sTNF-R1 and sTNF-R2) were described to influence the post-traumatic inflammatory response and organ dysfunction. METHOD: From 47 trauma patients, blood samples were obtained at the scene of accident, at hospital admission, after 4 h, 12 h, and 24 h, and daily until day 6. Plasma levels of TNFalpha, sTNFR1 and sTNF-R2 were measured by enzyme immunoassay (EIA) and analysed comparing clinical parameters such as injury scores (ISS, AIS), development of multiple organ dysfunction syndrome (MODS) and/or systemic inflammatory response syndrome (SIRS), and outcome. RESULTS: Significant changes were observed in a time-dependent manner: TNFalpha and soluble TNF receptor levels were elevated compared to values of healthy persons. At 4 h after trauma, TNFalpha and sTNF-R2 showed an increase from initial values, which continued during the entire observation period. Severe trauma led to enhanced sTNF-R1 levels on scene and on hospital admission. Development of SIRS along with elevated sTNF-R1 began on scene and was present on admission, with increased sTNF-R2 from day 1 to day 4. MODS (until day 6) was preceded by increased sTNF-R2 levels on admission and up to 4 h after trauma. Outcome was associated neither with TNFalpha nor with soluble TNF receptor levels. CONCLUSION: Thus, in trauma patients, early post-traumatic MODS and SIRS coincide with increased levels of TNFalpha and TNF receptor proteins, revealing different, time-dependent changes. Hence, detection of TNFalpha and soluble TNF receptor proteins after trauma should pay regard to the time point of sampling.

Adolescent↗

Nasal, pulmonary and autoinhaled nitric oxide at rest and during moderate exercise.

OBJECTIVE: To investigate nasal nitric oxide (NO) excretion, pulmonary NO excretion, and autoinhalation of nasally released NO at rest compared with that during moderate exercise in smokers and non-smokers. DESIGN: Prospective observational study. SETTING: University laboratory. PARTICIPANTS: Fourteen healthy adult volunteers. INTERVENTIONS: Breathing of NO-purified air supplied via a tube system at rest and during a bicycle-ergometer workload of 60 Watt over a time of 10 min. MEASUREMENT AND RESULTS: We examined nasal and pulmonary NO excretion in smoking (n = 7) and non-smoking (n = 7) adult human volunteers. At rest, we measured constant nasal NO excretion rates of 311 +/- 89 nl/min for non-smokers and 261 +/- 142 nl/min for smokers (mean +/- SD, n.s.). During 60 W exercise, nasal NO release remained unchanged, while pulmonary NO excretion doubled compared with the rates at rest (non-smokers: 40 +/- 21 nl/min versus 23 +/- 14 nl/min, p < 0.05; smokers: 41 +/- 8 nl/min versus 22 +/- 8 nl/min, p < 0.05). The differences between smokers and non-smokers in nasal or pulmonary NO excretion were not significant. To determine the autoinhaled amount of nasally released NO, we also measured the NO concentration within the nasopharynx of five volunteers during nasal breathing. The average inhaled NO concentration was 17.8 +/- 3.1 ppb at rest and this decreased to 9.3 +/- 1.8 ppb during exercise of 60 W, while minute ventilation approximately doubled from 9 +/- 2 to 21 +/- 3 l/min. CONCLUSION: Our results demonstrate that moderate exercise increased exclusively pulmonary NO excretion. Nasal NO release, which is 10 times higher at rest, was not changed. The decrease in autoinhaled NO concentration during exercise results from dilution of the continuous nasal release by the increased respiratory gas flow. The individual NO release allows no conclusion about smoking habits.

Adult↗

Whole body hyperthermia: a secure procedure for patients with various malignancies?

OBJECTIVE: To establish the safety of systemic Cancer Multistep Therapy (sCMT) including whole body hyperthermia, by means of hemodynamic, laboratory and clinical investigations. DESIGN: Prospective study. SETTING: University clinic. PATIENTS: 12 patients with various cancers (with sCMT), a second group of 20 patients with colorectal carcinoma treated with chemotherapy (without sCMT). INTERVENTIONS: 25 treatments with sCMT for 60 min at 41.8 degrees C (including chemotherapy) were given in addition to induced hyperoxemia and hyperglycemia under general anesthesia. MEASUREMENTS AND RESULTS: Invasive monitoring of systemic and pulmonary hemodynamics as well as pulmonary gas exchange was used at 37 degrees C, 40 degrees C, 41.8 degrees C and 39 degrees C. In addition, laboratory parameters were measured before and within 4 days of therapy. At 41.8 degrees C, invasive monitoring showed characteristic signs of hyperdynamic circulation. In addition, right-to-left shunt, oxygen consumption, oxygen delivery and lactate levels were significantly different from pretreatment values. At the end of therapy, lactate levels and the extravascular lung water index increased, whereas all other parameters showed a clear tendency to return to initial values. Within the first day after sCMT, we measured a slight but significant reversible increase in serum creatinine compared to pretreatment values, but found no significant alterations of other chemical parameters. Between the sCMT group and controls, there was only a temporary significant difference in aspartate aminotransferase levels 2 days after therapy. CONCLUSIONS: sCMT, including whole body hyperthermia, accompanied by suitable anesthesiological management and monitoring, does not lead to any serious or sustained organ dysfunction and can therefore be regarded as a safe therapy.

Adult↗

Exhaled nitric oxide in patients with Wegener's granulomatosis.

In Wegener's granulomatosis (WG), a pathogenic role of infections, in particular of a chronic colonization of the nasal mucosa with Staphylococcus aureus, has been postulated. Nitric oxide (NO), which is thought to play a role in primary host defence and inflammation, is produced endogenously within the respiratory tract, mainly from the paranasal sinuses. In order to further characterize its role in WG, nasal and pulmonary NO excretion in WG patients in comparison to healthy volunteers was measured. Seventeen patients with WG were included in the study. Five patients had active disease (bloody rhinitis with ulceration and crusting) and immunosuppressive therapy (IST), and 12 were in remission (six with, and six without, IST). S. aureus was found in the swabs of all patients with active WG and in three patients in remission. NO was measured in exhaled gas using a chemiluminescence analyser. The NO excretion rate in nasally sampled gas was significantly reduced (p<0.05) in patients with active WG ((mean+/-SD)102+/-100 nL x min(-1)) compared to healthy controls (299+/-13 nL x min(-1)), and patients in remission (281+/-86 nL x min(-1) with IST, 280+/-133 nL x min(-1) without IST). Pulmonary NO excretion in active or nonactive WG patients did not significantly differ from that of healthy volunteers (48+/-21 nL x min(-1)). These results demonstrate a reduced nasal NO excretion in active Wegener's granulomatosis. This may be caused by destruction and/or functional impairment of sinus epithelium. The reduced NO concentration may well compromise host defence in the upper airways, thus contributing to colonization with Staphylococcus aureus and further promoting Wegener's granulomatosis.

Adult↗

Nitric oxide diffusion across membrane lungs protects platelets during simulated extracorporeal circulation.

BACKGROUND: The absence of a protective endothelial surface on membrane oxygenators during extracorporeal circulation (ECC) promotes platelet trapping and damage, leading to increased bleeding complications. We investigated the effects of transmembranous diffusion of gaseous nitric oxide (NO) on platelets during simulated ECC. MATERIAL AND METHODS: Two paired circuits were run in parallel with fresh, heparinized (1 U mL-1) blood from healthy human donors for 240 min. To one of the paired circuits, 20 ppm NO was added transmembranously. RESULTS: NO significantly attenuated platelet trapping and reduced intracircuit platelet activation evaluated by the release of beta-thromboglobulin, platelet factor 4 and soluble P-selectin. Furthermore, NO significantly preserved platelet reactivity to stimulating agents (ADP and adrenaline), evaluated as the ability to expose P-selectins and activate glycoprotein (GP)-IIb-IIIa. Nevertheless, circulating activated platelets expressing P-selectin or activated GPIIb-IIIa were not different and were not significantly increased. The mean fluorescence intensity of GPIb and GPIIb-IIIa decreased in both circuits equally. CONCLUSIONS: Transmembranous diffusion of gaseous NO revealed protective effects on platelets by reducing thrombocytopenia/pathia and preserving platelet reactivity.

Adenosine Diphosphate↗

L-selectin in trauma patients: a marker for organ dysfunction and outcome?

BACKGROUND: Systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndrome (MODS) are important factors affecting morbidity and mortality after trauma. Adhesion molecules, e.g. L-selectin (CD62 L), play crucial roles in both conditions. PATIENTS AND METHODS: In 51 multiple trauma patients, CD62 L surface expression on granulocytes, monocytes, lymphocytes, as well as sCD62 L plasma concentrations were determined during the first 6 days after trauma, starting at the site of accident. Clinical parameters were severity of injury scores (ISS, APACHE II), requirement of red blood cell transfusion, acute lung or liver failure, development of MODS or SIRS, early (< or = 6 d) or late (> 6 d), and outcome. RESULTS: CD62 L expression was reversibly elevated on granulocytes, T cells and monocytes in comparison with initial values. sCD62 L plasma concentrations did not show temporal variations but were depressed throughout observation period, in comparison with healthy controls. Lung failure within the first 6 days was associated with increased CD62 L expression on monocytes and B cells on admission and increased sCD62 L concentrations after 12 and 24 h. Patients with more severe injuries (APACHE II > 20 points) had higher sCD62 L concentrations after 24 h. Non-survivors had decreased sCD62 L (on admission) and T-cell CD62 L expression (after 4 h). Patients with early MODS or SIRS showed increased monocyte CD62 L expression after 6 days. CONCLUSIONS: In multiple trauma patients, severe organ dysfunction is associated with altered CD62 L expression on leukocytes and circulating sCD62 L plasma concentrations. However, the obvious complexity of the pattern currently restricts use of CD62 L quantitation for clinical purposes.

Adolescent↗

[Polyomavirus infections in exotic birds in Switzerland].

Polyomavirus infections in budgerigars, in other parrots as well as in passeriformes have been described in many countries, but not in Switzerland so far. This paper reports on cases of polyomavirus infections in three different bird collections in Switzerland. The first outbreak occurred in a mixed collection of passeriformes, the second in a collection of parrotlets (Genus Forpus), and the third in a large groups of parrots (Psittaciformes), of which only one recently acquired Kea (Nestor notabilis) was affected. The clinical symptoms, gross necropsy changes and histopathologic findings are described. The presence of avian polyomavirus was confirmed by the polymerase chain reaction (PCR).

Animals↗

[Hospital hygiene--an essential aspect of quality assurance. Results of a survey in the hospitals of the German state of Saxony].

The committee of quality assurance in diagnostic and therapy at the General Medical Council of Saxony founded 1996 in a team consisting of full-time hygienists in order to investigate the situation concerning hospital hygiene within the German state Saxony. Therefore, a survey was worked out and sent to all hospitals as a common activity of the General Medical Council of Saxony and the Hospital Federation of Saxony in order to get complete and reliable data. The evaluation of the survey results in a lower rate of participation compared with a former investigation in 1992/93. However, it could be proved that hospital hygiene gained importance over the last years. At least the general requirements to work on the field of hospital hygiene are available. This is proven by the fact that infection control physicians are appointed and hygiene plans are existing in all hospitals. In 96.6% of the hospitals, hygiene committees are working, 93.3% of the hospitals document nosocomial infections and 90% of the hospitals have hygiene experts in the meaning of appropriate qualified employees. On the other side, the survey indicates potentials for improvement. Only 8.8% of the infection control physicians have a defined time at their own disposal. In addition, in hygiene specialists are involved in questions of building planning or of buying medical products with hygienic relation less than half of the hospitals. It is obvious that the survey could only affect some of the essential problems concerning hospital hygiene. A more profound analysis needs more questions and therefore more time to answer. At least, this survey reached the aim to reproduce and to illustrate the situation of hospital hygiene in the German state Saxony and promotes the discussion within the hospitals and the different committees.

Cross Infection↗

Morphological changes in chest radiographs of patients with acute respiratory distress syndrome (ARDS).

OBJECTIVE: To determine whether the quality of infiltrations in chest radiographs can accurately predict the histological extent of fibrotic change in patients with acute respiratory distress syndrome (ARDS). DESIGN: Retrospective clinical investigation. SETTING: Intensive care unit (ICU) of a university teaching hospital. PATIENTS AND METHODS: Of 47 patients treated with extracorporeal membrane oxygenation (ECMO) for severe ARDS over a 5-year period, 23 patients underwent open lung biopsy at thoracotomy for treatment, mostly of pneumothorax. Chest films obtained by portable chest roentgenography preceding the operation were reviewed retrospectively and compared to the histomorphological results of the lung specimen. RESULTS: Chest radiographs displayed mixed alveolar-reticular opacification in 60.2%, alveolar patterns in 22.9% and reticular opacities in 10.5%. In 0.4% there were no infiltrates, 6% could not be evaluated because of insufficient quality. There was no relevant difference between the right and left lungs. Subdividing patients into two groups according to the histological results of either absent or mild (1) or severe (2) lung fibrosis, we found an alveolar haziness in 12.3% in group 1 compared with 28.2% in group 2, while reticular characteristics were identified in 13% and 11%, respectively. CONCLUSIONS: The most common opacity in chest radiographs of patients with severe ARDS treated with ECMO is mixed alveolar-reticular opacification. Severe lung fibrosis is not positively correlated with a reticular radiographic pattern. ECMO does not lead to specific radiological changes in conventional radiograms, contrary to clinical findings that treatment with ECMO might induce pleural or pulmonic haemorrhage, especially in the earlier days when systemic heparinization had to be used instead of the heparin-coated tube-surfacing.

Adolescent↗

Nitric oxide inhibits tissue factor synthesis, expression and activity in human monocytes by prior formation of peroxynitrite.

OBJECTIVE: Nitric oxide (NO) has antithrombotic properties by regulating platelet function, whereas direct effects on plasmatic coagulation are rarely described. In sepsis and inflammation, when synthesis of NO, oxygen radicals and toxic metabolites is crucial, the expression of tissue factor (TF) on monocytes stimulated by lipopolysaccharides (LPS) induces intravascular coagulation. This study was performed to examine the influence of NO and the NO-dependent metabolite peroxynitrite on LPS-induced TF expression and activity in human monocytes. DESIGN: Experimental study. SETTING: Laboratory for cell biology. METHODS: Human peripheral blood mononuclear cells were isolated from buffy coats by gradient centrifugation. The NO-releasing compounds SIN1 and NOC18 were used under different conditions. TF antigen was assayed by flow cytometry, and its activity by a clotting assay. TF-mRNA was measured by reverse transcriptase polymerase chain reaction (RT-PCR-ELISA). MEASUREMENTS AND RESULTS: Whereas NOC18, a pure NO donor, had no effect, SIN1, releasing both NO and superoxide (O2-), reduced TF expression and activity in a dose- and time-dependent manner; superoxide dismutase (SOD) reversed the SIN1-mediated effect. Adding the O2(-)-deliberating system hypoxanthin/xanthin oxidase (which had no significant effect per se) to NOC18, or using the NO and O2- reaction product peroxynitrite resulted in a reduction of TF expression. RT-PCR-ELISA indicated upregulation of TF-mRNA by SIN1 with a peak at 500 microM; higher doses had less effect. CONCLUSION: These data demonstrate an influence of NO on LPS-induced TF expression in monocytes by prior formation of peroxynitrite; furthermore, the balance between NO and O2- seems to play a crucial role.

Dose-Response Relationship, Drug↗

Decreased soluble adhesion molecule L-selectin plasma concentrations after major trauma.

BACKGROUND: Binding of the leukocyte glycoprotein L-selectin to ligands expressed by activated endothelium directs leukocyte recruitment to areas of acute inflammation. Sequestration by activated microvascular endothelium has been proposed to explain the low plasma concentrations of soluble L-selectin (sCD62L) observed early in patients with acute respiratory distress syndrome. We hypothesized that inflammatory endothelial activation may occur in trauma patients, leading to decreased sCD62L plasma concentrations. METHODS: This study was a prospective analysis of sCD62L plasma concentrations in patients with isolated head injuries and multiple trauma patients without head injuries admitted to two tertiary-level intensive care units. sCD62L plasma concentrations were determined in 18 consecutive adult patients with isolated moderate and severe head injuries and in 13 multiple trauma patients without head injuries immediately upon admission to the intensive care unit and then daily for up to 10 days after trauma. RESULTS: Compared with healthy adult controls (n=22), patient sCD62L plasma concentrations were significantly decreased upon admission (5.7+/-1.6 vs. 11.0+/-1.7 pmol/mL; p < 0.001). In all patients, sCD62L concentrations remained depressed throughout the study period. sCD62L concentrations did not differ significantly between patients with isolated head injuries and multiple trauma patients without head injuries, although repeated-measures analysis of variance showed significantly more depressed sCD62L concentrations associated with severe (n=14) compared with moderate head injuries (n=4) during the study period (p < 0.05). CONCLUSION: Patients with major trauma present with a significant reduction of sCD62L plasma concentrations within the first 12 hours after trauma and during subsequent intensive care. This finding suggests widespread microvascular endothelial activation after trauma, which may be associated with increased neutrophil extravasation.

Adolescent↗

One peptide, two topologies: structure and interconversion dynamics of human uroguanylin isomers.

The peptide hormone uroguanylin stimulates chloride secretion via activation of intestinal guanylyl cyclase C (GC-C). It is characterized by two disulfide bonds in a 1-3/2-4 pattern that causes the existence of two topological stereoisomers of which only one induces intracellular cGMP elevation. To obtain an unambiguous structure-function relationship of the isomers, we determined the solution structure of the separated uroguanylin isoforms using NMR spectroscopy. Both isomers adopt well-defined structures that correspond to those of the isomers of the related peptide guanylin. Furthermore, the structure of the GC-C-activating uroguanylin isomer A closely resembles the structure of the agonistic Escherichia coli heat-stable enterotoxin. Compared with guanylin isomers, the conformational interconversion of uroguanylin isomers is retarded significantly. As judged from chromatography and NMR spectroscopy, both uroguanylin isoforms are stable at low temperatures, but are subject to a slow pH-dependent mutual isomerization at 37 degrees C with an equilibrium isomer ratio of approximately 1:1. The conformational exchange is most likely under the sterical control of the carboxy-terminal leucine. These results imply that GC-C is activated by ligands exhibiting the molecular framework corresponding to the structure of uroguanylin isomer A.

Amino Acid Sequence↗

Low nitric oxide concentrations in exhaled gas and nasal airways of mammals without paranasal sinuses.

To investigate whether relevant levels of nasal nitric oxide (NO) are produced in the absence of paranasal sinuses, we studied 17 healthy baboons, mammals without any paranasal sinuses. The animals were anesthetized with ketamine hydrochloride and breathed spontaneously. While the baboons breathed through a face mask (mouths closed) connected to a respirator, NO concentrations in exhaled gas were sampled from the expiratory limb and analyzed by chemiluminescence. While the animals were breathing ambient air, nasal gas was sampled via a thin plastic tube and analyzed for NO concentrations by chemiluminescence. Mean NO concentration in the exhaled gas was 1.00 +/- 0.59 parts/billion, and NO release was 4.28 +/- 2.72 nl/min. A NO concentration of 4.79 +/- 2.08 parts/billion was found in the nasal gas (NO release: 7.18 +/- 3.13 nl/min). An age-dependent increase in nasal NO levels was not observed. Exhaled and nasal NO concentrations in baboons were markedly lower than in mammals with paranasal sinuses, suggesting that paranasal sinuses might be an anatomic requirement for production of relevant nasal NO levels.

Animals↗

High survival rate in 122 ARDS patients managed according to a clinical algorithm including extracorporeal membrane oxygenation.

OBJECTIVE: We investigated whether a treatment according to a clinical algorithm could improve the low survival rates in acute respiratory distress syndrome (ARDS). DESIGN: Uncontrolled prospective trial. SETTING: One university hospital intensive care department. PATIENTS AND PARTICIPANTS: 122 patients with ARDS, consecutively admitted to the ICU. INTERVENTIONS: ARDS was treated according to a criteria-defined clinical algorithm. The algorithm distinguished two main treatment groups: The AT-sine-ECMO (advanced treatment without extracorporeal membrane oxygenation) groups (n = 73) received a treatment consisting of a set of advanced non-invasive treatment options, the ECMO treatment group (n = 49) received additional extracorporeal membrane oxygenation (ECMO) using heparin-coated systems. MEASUREMENTS AND RESULTS: The groups differed in both APACHE II (16 +/- 5 vs 18 +/- 5 points, p = 0.01) and Murray scores (3.2 +/- 0.3 vs 3.4 +/- 0.3 points, p = 0.0001), the duration of mechanical ventilation prior to admission (10 +/- 9 vs 13 +/- 9 days, p = 0.0151), and length of ICU stay in Berlin (31 +/- 17 vs 50 +/- 36 days, p = 0.0016). Initial PaO2/FIO2 was 86 +/- 27 mm Hg in AT-sine-ECMO patients that improved to 165 +/- 107 mm Hg on ICU day 1, while ECMO patients showed an initial PaO2/FIO2 of 67 +/- 28 mm Hg and improvement to 160 +/- 102 mm Hg was not reached until ICU day 13. QS/QT was significantly higher in the ECMO-treated group and exceeded 50% during the first 14 ICU days. The overall survival rate in our 122 ARDS patients was 75%. Survival rates were 89% in the AT-sine ECMO group and 55% in the ECMO treatment group (p = 0.0000). CONCLUSIONS: We conclude that patients with ARDS can be successfully treated with the clinical algorithm and high survival rates can be achieved.

Adult↗

Extracorporeal membrane oxygenation for transport of hypoxaemic patients with severe ARDS.

Conventional inter-hospital transfer of patients with severe acute respiratory distress syndrome (ARDS) in need of extracorporeal membrane oxygenation (ECMO) may be risky and in severe hypoxaemic patients may be associated with cerebral hypoxia and death. Therefore, we began a phase 1 study to evaluate the feasibility, complications and outcome of inter-hospital transport of these patients using veno-venous ECMO. Eight patients with severe ARDS and a PaO2/FIO2 < 6.7 kPa at a PEEP > or = 10 cm H2O were placed on a mobile ECMO at the referring hospital. The 495 (SD 123) km inter-hospital transport via a special ground ambulance took 341 (151) min. After transfer, blood-gas tensions were improved in spite of less optimal ventilator settings, compared with data before the start of ECMO. No significant complications occurred. Six patients survived and were discharged from hospital; two patients died because of multiple organ failure. We conclude that initiation of ECMO in hypoxaemic patients before inter-hospital transfer is feasible and enables safe transport to an ECMO centre.

Adult↗

Inhaled nitric oxide does not change transpulmonary angiotensin II formation in patients with acute respiratory distress syndrome.

STUDY OBJECTIVE: To investigate the effect of short-term inhalation of nitric oxide (NO) on transpulmonary angiotensin II formation in patients with severe ARDS. DESIGN: Prospective, clinical study. SETTING: Anesthesiology ICU of a university hospital. PATIENTS: Ten ARDS patients who responded to inhalation of 100 ppm NO by decreasing their pulmonary vascular resistance (PVR) by at least 20 dyne x s x cm(-5) were included in the study. INTERVENTIONS AND MEASUREMENTS: In addition to standard treatment, the patients inhaled 0, 1, and 100 ppm NO in 20-min intervals. Fraction of inspired oxygen was 1.0. Hemodynamics were measured and recorded online. Mixed venous (pulmonary arterial catheter) and arterial (arterial catheter) blood samples were taken simultaneously for hormonal analyses at the end of each inhalation period. RESULTS: Pulmonary arterial pressure decreased from 33+/-2 mm Hg (0 ppm NO, mean+/-SEM) to 29+/-2 mm Hg (1 ppm NO, p<0.05), and to 27+/-2 mm Hg (100 ppm NO, p<0.05, vs 0 ppm). PVR decreased from 298+/-56 (0 ppm NO) to 243+/-45 dyne x s x cm(-5) (1 ppm NO, not significant [NS]), and to 197+/-34 dyne x s x cm(-5) (100 ppm NO, p<0.05, vs 0 ppm). Arterial oxygen pressure increased from 174+/-23 mm Hg (0 ppm NO) to 205+/-26 mm Hg (1 ppm NO, NS), and to 245+/-25 mm Hg (100 ppm NO, p <0.05, vs 0 ppm). Mean plasma angiotensin II concentrations were 85+/-20 (arterial) and 57+/-13 pg/mL (mixed venous) during 0 ppm NO and did not change during inhalation of 1 and 100 ppm NO. Mean transpulmonary plasma angiotensin II concentration gradient (=difference between arterial and mixed venous blood values) was 28+/-8 pg/mL (range, 0 to 69) during 0 ppm NO and did not change during inhalation of 1 and 100 ppm NO. Mean transpulmonary angiotensin II formation (transpulmonary angiotensin II gradient multiplied with the cardiac index) was 117+/-39 ng/min/m2 (range, 0 to 414) during 0 ppm NO and did not change during inhalation of 1 and 100 ppm NO. Mean arterial plasma cyclic guanosine monophosphate concentration was 11+/-2 pmol/mL (0 ppm NO), did not change during 1 ppm NO, and increased to 58+/-8 pmol/mL (100 ppm NO, p<0.05). Arterial plasma concentrations of aldosterone (142+/-47 pg/mL), atrial natriuretic peptide (114+/-34 pg/mL), angiotensin-converting enzyme (30+/-5 U/L), and plasma renin activity (94+/-26 ng/mL/h of angiotensin I) did not change. CONCLUSION: The decrease of PVR by short-term NO inhalation in ARDS patients was not accompanied by changes in transpulmonary angiotensin II formation. Our results do not support any relationship between transpulmonary angiotensin II formation and the decrease in PVR induced by inhaled NO.

Administration, Inhalation↗

Global and extended coagulation monitoring during extracorporeal lung assist with heparin-coated systems in ARDS patients.

Heparin-coated systems for extracorporeal lung-assist (ECLA) were developed to reduce hemorrhagic risk by lowering the systemic heparinization, monitored by global tests, e.g. activated coagulation time (ACT) and activated partial thromboplastin time (APTT). Since this strategy gives no insight into procoagulant states, five ARDS patients receiving ECLA with heparin-coated systems were investivated for changes in coagulation using both global and extended tests. During ECLA onset the APTT and ACT were within or near normal ranges, platelets decreased 76.5% within 48 h, fibrinogen decreased 28.7%, thrombin-antithrombin-III complexes were elevated before ECLA (53 micrograms/L), but demonstrated an additional peak (238 micrograms/L), plasminogen-activator-inhibitor-1 increased 12-fold, and the C1-inhibitor dropped 14.1%. In conclusion, after the onset of ECLA from a previous prethrombotic state, the precoagulant, anticoagulant, fibrinolytic and complement systems were activated in a similar way to that reported for non-heparinized systems with high-dose heparin. This was however only monitored by an extended test panel which was unable to predict thromboembolic events during ECLA.

Adult↗