PubMed Health⌕ Search

Biomedical subjects

M Haller

Publications and source records attributed to M Haller.

At least 19 recordsLinked to original sources

[Dissociative stupor as a postoperative consequence of general anesthesia].

A 31-year-old woman failed to awaken after an uneventful general anesthesia (propofol, alfentanil and 65% N2O in oxygen) for laparoscopic resection of an ovarian cyst. After the operation she was extubated and vital signs were stable. However, the patient remained unresponsive even to painful stimuli for about 2 h. Just before we performed a computed tomogram of the brain to exclude a cerebral lesion we noticed that she blinked. We hypothesized that unconsciousness was due to a dissociative stupor. After administration of sublingual lorazepam the patient woke up promptly and was alert and normal for the rest of the hospital stay. In conclusion, after exclusion of a pharmacological or organic cause for postoperative unconsciousness, dissociative stupor may be a reason for apparent coma after general anesthesia.

Adult↗

Single-injection inulin clearance for routine measurement of glomerular filtration rate in cats.

Glomerular filtration rate (GFR) was determined in 53 cats using an inulin single-injection method. Thirty healthy young adult cats were used to establish normal values. The procedure was also used in 23 cats that were either older than 10 years or had borderline serum creatinine levels. The total clearance was calculated from the decay of the serum inulin concentration after injection of 3000 mg/m(2)body surface area using a two-compartment model. Concomitant inulin and iohexol clearance in nine cats showed excellent correlation between the two methods. Calculated normal values for GFR in 30 healthy cats were 35.9-58.5 (median 46.0) ml/min/m(2)or 2.07-3.69 (median 2.72) ml/min/kg. A few cats with normal creatinine or blood urea nitrogen levels were detected as having reduced GFR and therefore being in a state of early renal dysfunction. The study indicates that single-injection inulin clearance is a valuable tool for routine GFR measurement in cats. An "inulin excretion test" using only one blood sample 3h after the administration of 3000 mg/m(2)body surface area could prove an attractive alternative for the assessment of renal function in daily practice.

Animals↗

Recurrent fever as the only or predominant clinical sign in four dogs and one cat with congenital portosystemic vascular anomalies.

Fever is not considered a typical clinical sign in animals with portosystemic vascular anomalies (PSVA). In a time period of 8 years, PSVA was diagnosed in 23 cases (20 dogs, 3 cats) at the Animal Hospital of the University of Zurich. Of these, recurrent fever was the only, the predominant or an early sign in 5 animals. Fever and associated unspecific clinical signs like lethargy, inappetence, and reluctance to move were present for weeks to months before the final diagnosis of PSVA was made. It was the lack of typical and well-known signs of PSVA that obscured and delayed the diagnosis. Therefore, PSVA should be included in the differential diagnosis of animals with fever of unknown origin (FUO).

Animals↗

How farmers in Switzerland perceive fertilizers from recycled anthropogenic nutrients (urine).

We studied acceptance of a urine-based fertilizer product using a mail survey of 467 Swiss farmers. We distinguished among four production types: organic or IP farming, and with or without vegetable production. Considering that the idea of urine-based fertilizers is new, acceptance among the answering farmers was surprisingly high, with 57% explicitly stating that they thought it was a good or very good idea, and 42% willing to purchase such a product. The farmers of different production types did not differ strongly in their attitude towards urine-based fertilizers. Especially IP and vegetable farmers, who purchased additional fertilizers anyway, seem willing to accept urine-based fertilizers, hereby preferring a grainy, odorless ammonium nitrate fertilizer. Absolutely essential is a hazard-free product: 30% of all farmers had concerns regarding micropollutants. Based on fertilizer data, we demonstrate an existing demand for the nutrients N, P, and K in Switzerland, which could be partially substituted by a recycled urine product. Finally, we discuss methodological requirements of social science surveys. To obtain representative data on an entire population in a mail survey, multiple contacts with respondents are necessary. We argue that information and participation of stakeholders at an early stage is essential for successful technology transfer.

Adult↗

Dynamic activation of K(ATP) channels in rhythmically active neurons.

1. The respiratory centre within the brainstem is one of the most active neuronal networks that generates ongoing rhythmic activity. Stabilization of such vital activity requires efficient processes for activity-correlated adjustment of neuronal excitability. Recent investigations have shown that a regulatory factor coupling electrical activity with cell metabolism comprises ATP-dependent K(+) channels (K(ATP) channels), which continuously adjust the excitability of respiratory neurons during normoxia and increasingly during hypoxia. 2. We used the single-cell antisense RNA amplification-polymerase chain reaction (PCR) technique to demonstrate that respiratory neurons co-express the sulphonylurea receptor SUR1 with the Kir6.2 potassium channel protein. 3. Single channel measurements on rhythmically active inspiratory neurons of the brainstem slice preparation of newborn mice revealed that K(ATP) channels are periodically activated in synchrony with each respiratory cycle. 4. The Na(+)-K(+)-ATPase was inhibited with ouabain to demonstrate that oscillations of the channel open probability disappear, although respiratory activity persists for a longer time. Such findings indicate that K(ATP) channel open probability reflects activity-dependent fluctuations in the ATP concentration within submembrane domains. 5. We also examined the effects of extracellular [K(+)] and hypoxia. All changes in the respiratory rhythm (i.e. changes in cycle length and burst durations) affected the periodic fluctuations of K(ATP) channel activity. 6. The data indicate that K(ATP) channels continuously modulate central respiratory neurons and contribute to periodic adjustment of neuronal excitability. Such dynamic adjustment of channel activity operates over a high range of metabolic demands, starting below physiological conditions and extending into pathological situations of energy depletion.

ATP-Binding Cassette Transporters↗

Continuous cardiac output measurements do not agree with conventional bolus thermodilution cardiac output determination.

PURPOSE: To evaluate the performance of two different continuous cardiac output monitoring systems based on the thermodilution principle in critically ill patients. METHODS: Nineteen cardiac surgical patients were randomly assigned to continuous cardiac output monitoring using one of the two systems under study (group I, IntelliCath(TM) catheter, n=9; group II, Opti-Q(TM) catheter, n=10). Each patient was studied over a period of three hours. Conventional bolus thermodilution cardiac output measurements were carried out every 15 min leading to 13 measurements in each patient. The continuous cardiac output values were compared with the bolus thermodilution measurements. Bias (mean difference between continuous and bolus thermodilution) and precision (SD of differences) were calculated as a measure of agreement between the respective continuous method and conventional bolus thermodilution. RESULTS: The range of measured cardiac outputs was 3.8-15.4 L*min(-1) (IntelliCath(TM)) and 3.5-8.3 L*min(-1) (OptiQ(TM)). Bias and precision was 0.06 +/- 0.76 L*min(-1) (IntelliCath(TM)) and -0.04 +/- 0.74 L*min(-1) (OptiQ(TM)), respectively. There was no difference in bias between the two systems (P=0.38). +/- 2 SD of the differences (i.e., 95% of the differences) did not fall within the predetermined limits of agreement of +/- 0.5 L*min(-1). CONCLUSIONS: There was no difference between the two systems regarding the agreement with conventional bolus thermodilution as the standard. A discrepancy between bolus and continuous thermodilution cardiac output measurement techniques above the clinically acceptable limits suggest that they are not interchangeable.

Adult↗

[The measurement of blood volume--state-of-the-art].

The term blood volume (BV) measurement can be understood as the exact volumetric definition of both components of blood, the red cell volume (RCV) and the plasma volume (PV) using tracer dilution methods. The tracer used to measure the RCV must be bound to the erythrocytes and for the PV to plasma proteins, in order to label the distribution space of each carrier (i.e. erythrocytes and albumin molecules). To differentiate this there are indirect methods to estimate the BV, such as measurement of the diastolic pressure or transoesophageal echocardiography, which will not be discussed here. Alterations in the RCV and PV cannot be routinely measured, or at most only roughly estimated by means of the haematocrit (Hc) or haemoglobin (Hb) concentration which can lead to serious errors when large changes have occurred. At present measurements of the RCV and PV are not carried out in routine clinical practice. The introduction of nonradioactive tracers with a faster elimination now renders possible a relatively exact measurement of both volumes under certain clinical situations, albeit with a high technical outlay. The RCV is measured using the tracer sodium fluorescein (SoF) and the PV with the dye indocyanine green (ICG). The RCV measurement seems to be suitable for certain clinical situations, such as characterization of the preoperative condition of a patient or quantification of surgical blood loss after an operation, because it is less invasive and has a high precision. However, the results of the RCV measurement can only be delivered after 1 h which makes it more suitable for clinically stable situations. In contrast the PV estimation is based on the measurement of the ICG concentration in the arterial bloodstream after a bolus injection of the dye in the central veins and is used more in intensive care because of the invasivity. The results can be obtained 5 min after injection of the dye and therefore even rapid changes in the PV can be monitored.

Blood Volume Determination↗

Changes in blood volume and hematocrit during acute preoperative volume loading with 5% albumin or 6% hetastarch solutions in patients before radical hysterectomy.

BACKGROUND: The impact of acute preoperative volume loading with colloids on blood volume has not been investigated sufficiently. METHODS: Before surgery, in 20 patients undergoing major gynecologic procedures, volume loading was performed during anesthesia by infusing approximately 20 ml/kg of colloid at a rate of 90 ml/min (group I: 5% albumin solution; group II: 6% hetastarch solution; n = 10 each). Plasma volume (indocyanine green dilution technique), erythrocyte volume (labeling erythrocytes with fluorescein), hematocrit, total protein, and hetastarch plasma concentrations (group II) were measured before and 30 min after the end of infusion. RESULTS: More than 1,350 ml of colloid (approximately 50% of the baseline plasma volume) were infused within 15 min. Thirty minutes after the infusion had been completed, blood volume was only 524 +/- 328 ml (group I) and 603 +/- 314 ml (group II) higher than before volume loading. The large vessel hematocrit (measured by centrifugation) dropped more than the whole body hematocrit, which was derived from double-label measurements of blood volume. CONCLUSIONS: The double-label measurements of blood volume performed showed that 30 min after the infusion of approximately 20 ml/kg of 5% albumin or 6% hetastarch solution (within 15 min), only mean 38 +/- 21% and 43 +/- 26%, respectively, of the volume applied remained in the intravascular space. Different, i.e., earlier or later, measuring points, different infusion volumes, infusion rates, plasma substitutes, or possibly different tracers for plasma volume measurement might lead to different results concerning the kinetics of fluid or colloid extravasation.

Adult↗

Intrinsic optical signals in respiratory brain stem regions of mice: neurotransmitters, neuromodulators, and metabolic stress.

In the rhythmic brain stem slice preparation, spontaneous respiratory activity is generated endogenously and can be recorded as output activity from hypoglossal XII rootlets. Here we combine these recordings with measurements of the intrinsic optical signal (IOS) of cells in the regions of the periambigual region and nucleus hypoglossus of the rhythmic slice preparation. The IOS, which reflects changes of infrared light transmittance and scattering, has been previously employed as an indirect sensor for activity-related changes in cell metabolism. The IOS is believed to be primarily caused by cell volume changes, but it has also been associated with other morphological changes such as dendritic beading during prolonged neuronal excitation or mitochondrial swelling. An increase of the extracellular K(+) concentration from 3 to 9 mM, as well as superfusion with hypotonic solution induced a marked increase of the IOS, whereas a decrease in extracellular K(+) or superfusion with hypertonic solution had the opposite effect. During tissue anoxia, elicited by superfusion of N(2)-gassed solution, the biphasic response of the respiratory activity was accompanied by a continuous rise in the IOS. On reoxygenation, the IOS returned to control levels. Cells located at the surface of the slice were observed to swell during periods of anoxia. The region of the nucleus hypoglossus exhibited faster and larger IOS changes than the periambigual region, which presumably reflects differences in sensitivities of these neurons to metabolic stress. To analyze the components of the hypoxic IOS response, we investigated the IOS after application of neurotransmitters known to be released in increasing amounts during hypoxia. Indeed, glutamate application induced an IOS increase, whereas adenosine slightly reduced the IOS. The IOS response to hypoxia was diminished after application of glutamate uptake blockers, indicating that glutamate contributes to the hypoxic IOS. Blockade of the Na(+)/K(+)-ATPase by ouabain did not provoke a hypoxia-like IOS change. The influences of K(ATP) channels were analyzed, because they contribute significantly to the modulation of neuronal excitability during hypoxia. IOS responses obtained during manipulation of K(ATP) channel activity could be explained only by implicating mitochondrial volume changes mediated by mitochondrial K(ATP) channels. In conclusion, the hypoxic IOS response can be interpreted as a result of cell and mitochondrial swelling. Cell swelling can be attributed to hypoxic release of neurotransmitters and neuromodulators and to inhibition of Na(+)/K(+)-pump activity.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

Molecular characterization of a cellulase-negative mutant of Hypocrea jecorina.

The "cbh2 activating element," CAE, consisting of two separate boxes (ATTGG = CCAAT and GTAATA, respectively) is essential for cellobiohydrolase II gene expression in the filamentous fungus Hypcrea jecorina. Here we report that cell-free extracts from a cellulase-negative mutant form CAE-protein complexes with higher mobility and lower binding-strength compared to the wild type. EMSA analysis demonstrated an increased mobility of the GTAATA-binding protein complex and, supported by in vivo footprinting, a lowered binding strength of the HAP2/3/5 proteins. However, the hap2/hap3/hap5 genes of the mutant are unaltered and transcribed normally. A nucleotide fragment of the cbh1 promoter containing a (GG)CTAATA motif without an adjacent CCAAT box is also bound by cell-free extracts of H. jecorina, and the protein-DNA complex of the mutant shows the characteristic increase in mobility. We conclude that this mutant is defective in the functional formation of the CAE-protein complexes but not in their binding to the target sequences itself.

Base Sequence↗

[Acute kidney failure. Physiopathology--clinical diagnosis--therapy].

Acute renal failure (ARF) is characterized by an acute decrease in glomerular filtration rate (GFR). ARF complicates 4% to 23% of intensive care unit admissions, and is associated with a mortality of approximately 50% among critically ill patients. In the intensive care setting the term ARF is usually applied to acute tubular necrosis (ATN), a form of intrinsic ARF caused by ischemia or nephrotoxins. Pathophysiological mechanisms involved in the decline in GFR include tubular obstruction caused by detachment of tubular epithelial cells from the basement membrane and back-leak of glomerular filtrate as a consequence of disruption of the epithelial cell layer. Vascular mechanisms involved in the pathophysiology of ATN are vasoconstriction due to an imbalance between vasoconstrictive and vasodilatory mediators and vascular obstruction caused by cell aggregation. Currently, there is no real time method to monitor renal function comparable to the real time monitoring of blood pressure or arterial oxygen saturation. Urinary output does not reflect glomerular filtration which may be critically reduced despite normal urine volumes and creatinine clearance still provides the clinically most applicable estimate of GFR. Tubular function can be assessed using the fractional excretion of sodium or the ratio of urinary and serum osmolality; both parameters can be obtained from spot samples of urine and serum and no urinary sampling period is necessary. However, both parameters are strongly affected by the administration of loop diuretics and high fluid and sodium inputs which are common in the intensive care unit. We determined the day to day variability of creatinine clearance, fractional excretion of sodium and the urinary to serum osmolality ratio in critically ill patients without renal dysfunction (i.e. creatinine clearance in the normal range) and found differences of 16% for creatinine clearance, 79% for fractional excretion of sodium and 22% for urinary to serum osmolality ratio. Treatment of ARF is mainly supportive and there is no clinically accepted therapy that attenuates the course of ATN. Treatment of the underlying disease and renal replacement therapy are the main options for the treatment of patients with ARF. In critically ill patients continuous venovenous hemo(dia)filtration is the first choice because it provides more hemodynamic and metabolic stability than intermittent therapy. Acute life-threatening hyperkalemia is an indication for intermittent hemodialysis because of the higher efficacy of dialysis in the clearance of low molecular weight substances.

Acute Kidney Injury↗

Pulmonary function and health-related quality of life in a sample of long-term survivors of the acute respiratory distress syndrome.

OBJECTIVE: We performed a follow-up cohort analysis in order to delineate the correlation between pulmonary function (PF) and health-related quality of life (HRQL) in patients after ARDS. DESIGN: Follow-up cohort study. SETTING: A 20-bed ICU of a university teaching hospital. PATIENTS: A cohort of 50 long-term survivors of ARDS. MEASUREMENTS AND RESULTS: Measurements of PF (FVC, FEV1, TLC, D(LCO)) and HRQL (SF-36 Health Status Questionnaire) were made 5.5 years (median value) after discharge from the ICU. Impairments in PF (defined as PF results below 80% of the predicted value) were frequent but generally mild. Twenty patients had a single PF impairment (with limitations in FEV1/FVC ratio in 12 patients being the most common), four patients had two (with D(LCO) and FEV1/FVC ratio impairment the most common) and three patients had pathologic results in three PF tests (FEV1/FVC ratio, TLC and capillary pO2 during exercise in one case, FVC, TLC and capillary pO2 during exercise in the second patient and FVC, TLC and D(LCO) in the third). Compared to normal controls, survivors of ARDS showed impairments in all SF-36 health dimensions (p < 0.001). Patients with multiple (> 1) PF impairments described the lowest HRQL with major limitations in all SF-36 categories (p < 0.037) including physical and mental summary scores (36.5 vs 46.9, p = 0.037 and 31.3 vs 51.4, p = 0.003) when compared to patients with no or only one PF impairment. CONCLUSIONS: Long-term survivors of ARDS have a significant reduction in HRQL and the presence of multiple PF impairments is associated with maximal decrements in HRQL.

Adult↗

Development of a knowledge-base for automatic monitoring of renal function of intensive care patients over time.

Renal dysfunction is a major problem in the management of critically ill patients. Monitoring of renal parameters over time is a prerequisite for detection of any significant deterioration of kidney function. Thus, we developed a knowledge-base for the dynamic monitoring of renal function of critically ill patients. A database with renal parameters of 750 intensive care patients was analyzed for distribution of parameters within predefined intervals of the creatinine clearance. Additionally, a subgroup of 11 patients with (quite) normal renal function over 11 days was selected and the daily variability of renal parameters was analyzed. An interdisciplinary expert team selected a set of nine clinically relevant renal parameters and formulated, on the basis of the data analysis and the parameter set, eight definitions of renal function, which represent four levels of renal performance. These definitions were arranged into an hierarchical structure, considering only clinically relevant changes of renal function. A change from one functional state to another inside of 2 days indicates a relevant alteration of renal function. Monitoring of time courses can additionally be performed by statistical analysis of the daily variability of parameters and comparison with their 'normal' variability. Moreover, rules were established for the plausibility check of results and interpretations of single parameters and parameter sets formulated.

Artificial Intelligence↗

Beat-to-beat measurement of cardiac output by intravascular pulse contour analysis: a prospective criterion standard study in patients after cardiac surgery.

OBJECTIVE: To evaluate the accuracy of a new pulse contour method of measuring cardiac output in critically ill patients. DESIGN: A prospective criterion standard study. SETTING: Cardiac surgery intensive care unit in a university hospital. PARTICIPANTS: Nineteen cardiac surgery patients requiring intensive care treatment with pulmonary artery catheters after surgery. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The pulse contour cardiac output monitor uses transpulmonary bolus thermodilution measurements to calibrate the system. In each patient, the pulse contour cardiac output values were compared with conventional thermodilution. The method described by Bland and Altman and linear regression analysis were used for comparison. The mean difference (bias) +/- standard deviation of differences (precision) was 0.31 +/- 1.25 L/min for pulmonary bolus thermodilution cardiac output versus pulse contour cardiac output and 0.21 +/- 0.73 L/min for pulmonary bolus thermodilution cardiac output versus transpulmonary bolus thermodilution cardiac output. Linear regression (correlation) analyses were pulse contour cardiac output = 0.97 thermodilution + 0.53 (r = 0.88), and transpulmonary cardiac output = 0.87 thermodilution + 1.09 (r = 0.96). There was a small increase 60 minutes after recalibration but not a statistically significant difference between pulse contour cardiac output and pulmonary bolus thermodilution cardiac output (p = 0.52). CONCLUSIONS: Bias and precision are acceptable, and the system provides results that agree with conventional thermodilution. This study demonstrates the clinical applicability of the pulse contour cardiac output monitoring system.

Adult↗

Changes in intravascular volume during acute normovolemic hemodilution and intraoperative retransfusion in patients with radical hysterectomy.

BACKGROUND: Changes in blood volume during acute normovolemic hemodilution (ANH) and their consequences for the perioperative period have not been investigated sufficiently. METHODS: In 15 patients undergoing radical hysterectomy, preoperative ANH to a hematocrit of 24% was performed using 5% albumin solution. Intraoperatively, saline 0.9% solution was used for volume substitution, and intraoperative retransfusion was started at a hematocrit of 20%. Plasma volume (indocyanine green dilution technique), hematocrit, and plasma protein concentration were measured before and after ANH, before retransfusion, and postoperatively. Red cell volume (labeling erythrocytes with fluorescein) was determined before and after ANH and postoperatively. RESULTS: Mean normal plasma volumes (1,514 +/- 143 ml/m2) and reduced red cell volumes (707 +/- 79 ml/m2) were measured preoperatively. Blood (1,150 +/- 196 ml) was removed and replaced with 1,333 +/- 204 ml of colloid. Blood volume before and after ANH was equal and amounted to 3,740 ml. Intraoperatively, plasma volume did not increase until retransfusion despite infusing 3,389 +/- 1,021 ml of crystalloid (corrected for urine output) to compensate for an estimated surgical blood loss of 727 +/- 726 mi. Postoperatively, after retransfusion of all autologous blood, blood volume was 255 +/- 424 ml higher than preoperatively before ANH. Despite mean calculated blood loss of 1,256 +/- 892 ml, only one patient received allogeneic blood. CONCLUSIONS: During ANH, normovolemia was exactly maintained. After surgical blood loss of 1,256 +/- 892 ml, crystalloid and colloid supplies of 5,752 +/- 1,462 ml and 1,667 +/- 548 ml, respectively, and complete intraoperative retransfusions of autologous blood in every patient, mean blood volume was 250 ml higher than preoperatively before ANH.

Adult↗

Liver transplantation in primary biliary cirrhosis: risk assessment and 11-year follow-up.

BACKGROUND/AIMS: Liver transplantation (LTx) is the only established treatment in patients with end-stage primary biliary cirrhosis (PBC). Although short-term survival after LTx in this group of patients is usually good, few data exist on the long-term survival. The optimal timing of transplantation is difficult. Thus, the aims of this study were to assess the long-term survival of patients with PBC after LTx and to identify potential predictive factors for a positive outcome. METHODS: Survival of 28 patients with PBC who underwent LTx between 1985 and July 1999 in a single center was studied by Kaplan-Meier analysis and was compared to predicted survival without LTx using established prognostic models for PBC, the Mayo and European risk scores. Potential prognostic parameters obtained before LTx were tested for correlation to survival. Rates of bone fractures as markers of hepatic osteodystrophy were compared before and after LTx. RESULTS: Median follow-up after LTx was 90 months with a maximum of 140 months. Actuarial survival of patients with PBC was 89% after 1, 5, and 10 years and was significantly better than estimated survival without LTx after 1-7 years as calculated by the Mayo and European risk scores. Of several parameters tested, only serum bilirubin and the prognostic scores, but no other liver function tests obtained immediately prior to transplantation were significantly correlated with survival after LTx. The duration of intensive care after LTx was not associated with any parameters obtained before LTx. Bone fractures were diagnosed in 43% of patients of whom the vast majority were osteopenic before LTx as determined by osteodensitometry. CONCLUSION: Long-term survival of a well-defined group of patients with PBC was excellent after LTx and was inversely correlated with preoperative serum bilirubin levels as well as Mayo and European risk scores.

Adult↗

Response to inhaled nitric oxide (NO) is not associated with changes of plasma cGMP levels in patients with acute lung injury.

BACKGROUND: A clinically relevant increase of PaO subset2 or decrease of pulmonary vascular resistance (PVR) upon inhalation of NO (iNO) does occur in only 60 to 80% of patients with acute lung injury. The mechanisms for divergent responses of different patients have not yet been fully elucidated. Since NO mediates its pulmonary effects by stimulating soluble guanylate cyclase, thereby increasing levels of cyclic guanosinemonophosphate (cGMP), we hypothesized that pulmonary cGMP production upon iNO might be suppressed in patients not responding to iNO treatment. METHODS: After approval by the local ethical committee and after informed consent had been obtained, both arterial and mixed-venous cGMP levels were analyzed in 13 patients in whom iNO was administered to treat pulmonary hypertension and/or hypoxemia due to acute respiratory distress syndrome (n = 11) or reperfusion injury following lung transplantation (n = 2). Both cardiorespiratory variables and cGMP concentrations were documented simultaneously at baseline, 15 min after inhalation of 8 ppm of NO, and 15 min after withdrawal of NO, respectively. RESULTS: Inhaled NO resulted in a significant increase in PaO(2)/FiO(2) and a decrease in PVR. Arterial and mixed venous concentration of cGMP (median) also increased significantly upon iNO from 2.5 to 6.5 nM (p <0.05) and from 3.0 to 5.7 nM (p <0.05), respectively. Theses effects were fully reversible after withdrawal of iNO. No gradients between arterial and mixed venous cGMP concentrations were detected (p = 0.12). Regression analysis showed no relationship between baseline arterial cGMP concentrations and changes of either PaO(2)/FiO(2) (p = 0. 62) or PVR (p = 0.91). Similarly, no relationship was found between the rise of arterial cGMP concentration subsequent to iNO and corresponding changes of PaO(2) (p = 0.40) or PVR (p = 0.74), respectively. CONCLUSION: Inhalation of NO significantly stimulates soluble guanylate cyclase within the lungs in patients with acute lung injury. However, neither baseline cGMP nor its rise during treatment with inhaled NO can predict the clinical efficacy of iNO in humans. Furthermore, the fact that increased cGMP concentrations were detected during administration of iNO in mixed venous blood (i.e. pulmonary inflow) strongly suggest that the pharmacological effects of iNO are not fully selective for the lungs, but may also affect extrapulmonary organs.

Acute Disease↗