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ABSTRACT: inflammatory reactions arise in reaction to a variety of pathogenic insults. The combination of inhaled nitric oxide (iNO) and glucocorticoids (GC) may attenuate endotoxin-induced inflammatory responses. It has been shown that the combination of iNO (30 p.p.m.) and steroids blunted the inflammatory response in a porcine endotoxin model, but not in humans. Therefore, we investigated whether a clinically 'maximal' dose of iNO in combination with GC could modulate the systemic inflammatory response in a human endotoxin model.
a double-blind, cross-over, placebo-controlled randomized study including 15 healthy Caucasian volunteers (five females, 10 males). Performed at the Intensive Care Unit in a university hospital. iNO 80 p.p.m. or placebo (nitrogen) was started 2h before administration of endotoxin (2 ng/kg). Thirty minutes later, GC (2mg/kg, hydrocortisone) was administered intravenously. Blood samples and clinical signs were collected before and up to 24 h after the endotoxin injection.
body temperature and heart rate increased significantly subsequent to endotoxin challenge. The plasma levels of IFN-γ, IL-1β, IL-2, 4 5, 6, 8, 10, 12, 13 and TNFα were markedly elevated. However, HMGB-1 and sRAGE were unaffected. No difference between placebo/GC and iNO/GC treatment was observed in the clinical or cytokine response, neither was there any difference between the first and the second exposure to endotoxin.
pre-treatment with iNO 80 p.p.m. along with GC (2mg/kg) administrated after the endotoxin challenge could not modulate the systemic inflammatory response in this model of human experimental inflammation.
Acta Anaesthesiologica Scandinavica 01/2011; 55(1):20-7. · 2.19 Impact Factor
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ABSTRACT: Little has been reported about intensive care of children in Sweden. The aims of this study are to (I) assess the number of admissions, types of diagnoses and length-of-stay (LOS) for all Swedish children admitted to intensive care during the years 1998-2001, and compare paediatric intensive care units (PICUs) with other intensive care units (adult ICUs) (II) assess immediate (ICU) and cumulative 5-year mortality and (III) determine the actual consumption of paediatric intensive care for the defined age group in Sweden.
Children between 6 months and 16 years of age admitted to intensive care in Sweden were included in a national multicentre, ambidirectional cohort study. In PICUs, data were also collected for infants aged 1-6 months. Survival data were retrieved from the National Files of Registration, 5 years after admission.
Eight-thousand sixty-three admissions for a total of 6661 patients were identified, corresponding to an admission rate of 1.59/1000 children per year. Median LOS was 1 day. ICU mortality was 2.1% and cumulative 5-year mortality rate was 5.6%. Forty-four per cent of all admissions were to a PICU.
This study has shown that Sweden has a low immediate ICU mortality, similar in adult ICU and PICU. Patients discharged alive from an ICU had a 20-fold increased mortality risk, compared with a control cohort for the 5-year period. Less than half of the paediatric patients admitted for intensive care in Sweden were cared for in a PICU. Studies are needed to evaluate whether a centralization of paediatric intensive care in Sweden would be beneficial to the paediatric population.
Acta Anaesthesiologica Scandinavica 10/2008; 52(8):1086-95. · 2.19 Impact Factor
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ABSTRACT: Background: Little has been reported about intensive care of children in Sweden. The aims of this study are to (I) assess the number of admissions, types of diagnoses and length-of-stay (LOS) for all Swedish children admitted to intensive care during the years 1998–2001, and compare paediatric intensive care units (PICUs) with other intensive care units (adult ICUs) (II) assess immediate (ICU) and cumulative 5-year mortality and (III) determine the actual consumption of paediatric intensive care for the defined age group in Sweden.Methods: Children between 6 months and 16 years of age admitted to intensive care in Sweden were included in a national multicentre, ambidirectional cohort study. In PICUs, data were also collected for infants aged 1–6 months. Survival data were retrieved from the National Files of Registration, 5 years after admission.Results: Eight-thousand sixty-three admissions for a total of 6661 patients were identified, corresponding to an admission rate of 1.59/1000 children per year. Median LOS was 1 day. ICU mortality was 2.1% and cumulative 5-year mortality rate was 5.6%. Forty-four per cent of all admissions were to a PICU.Conclusions: This study has shown that Sweden has a low immediate ICU mortality, similar in adult ICU and PICU. Patients discharged alive from an ICU had a 20-fold increased mortality risk, compared with a control cohort for the 5-year period. Less than half of the paediatric patients admitted for intensive care in Sweden were cared for in a PICU. Studies are needed to evaluate whether a centralization of paediatric intensive care in Sweden would be beneficial to the paediatric population.
Acta Anaesthesiologica Scandinavica 08/2008; 52(8):1086 - 1095. · 2.19 Impact Factor
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Acta Anaesthesiologica Scandinavica 11/2007; 51(9):1136-7. · 2.19 Impact Factor
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ABSTRACT: The Respiratory Unit (RU) at Danderyd University Hospital opened in 1982, with the expressed goal of supporting outpatients with long-term tracheostomy. The primary aim of this retrospective study in tracheostomized patients was to compare the need for hospital care in the 2-year period before and after the tracheostomy.
Data were collected from patient medical records at the RU, from the National Board of Health and Welfare, Sweden and from the Official Statistics of Sweden. The subjects were RU patients in 1982 (Group 1, n = 27) and in 1997 (Group 2, n = 106) with long-term tracheostomy surviving at least 4 years after the tracheostomy.
Both groups had few and unchanged needs for hospital care after tracheostomy. They spent > or = 96% of their time out of hospital. In 1997, (group 2) the number of patients, diagnoses and need for home mechanical ventilation had increased. Life expectancy was assessed for patients in Group 1. Data showed that they lived as long as an age-matched and gender-adjusted control cohort.
Long-term tracheostomy may not increase the need for hospital care and does not reduce life expectancy. These clinical observations were made in a setting where patients had regular access to a dedicated outpatient unit.
Acta Anaesthesiologica Scandinavica 04/2006; 50(4):399-406. · 2.19 Impact Factor
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Critical Care - CRIT CARE. 01/2005; 9.
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ABSTRACT: Roughly 400.000 cases of sepsis occur every year in the United States only and this is associated with a very high mortality. Bacterial lipopolysaccharide (LPS) triggers systemic inflammatory reactions in sepsis. However, down-stream cellular cascade initiated by LPS is still being elucidated. Nitric oxide (NO) and matrix metalloproteinases-2 and -9 (MMP-2 and MMP-9) are known to be induced by LPS. We have investigated the release of NO, MMP-2 and MMP-9 following infusion of LPS to volunteers.
IPS (2 ng kg-1) was infused to 10 healthy volunteers. Before the experiments were started the subjects had an intravenous catheters placed. An electrocardiogram was also placed and monitored constantly. Body temperature was measured by ear thermometer every 10 min Venous blood was collected and cell-free plasma assayed for the presence of MMP-2 and MMP-9 using zymography and NO using HPLC assay for NO metabolites, nitrite and nitrate.
The administration of LPS resulted in increased body temperature and tachycardia. Time-dependent release of MMP-9(30 fold increase from the baseline) peaking at 2 h following infusion of LPS was observed. LPS did not significantly modify the activity of MMP-2 (P > 0.05). Infusion of LPS did not significantly change the levels of nitrite and nitrate (from 60 +/- 11 to 67 +/- 10 micro m, P > 0.05).
The release of MMP-9, but not MMP-2 or NO, is a sensitive index of endotoxaemia in humans. MMP-9 release may contribute to the pathogenesis of sepsis via its pro-inflammatory effects on the vasculature.
Acta Anaesthesiologica Scandinavica 04/2003; 47(4):407-10. · 2.19 Impact Factor
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ABSTRACT: Background: Roughly 400 000 cases of sepsis occur every year in the United States only and this is associated with a very high mortality. Bacterial lipopolysaccharide (LPS) triggers systemic inflammatory reactions in sepsis. However, down-stream cellular cascade initiated by LPS is still being elucidated. Nitric oxide (NO) and matrix metalloproteinases-2 and -9 (MMP-2 and MMP-9) are known to be induced by LPS. We have inves-tigated the release of NO, MMP-2 and MMP-9 following infusion of LPS to volunteers. Methods: IPS (2 ng kg À1) was infused to 10 healthy volunteers. Before the experiments were started the subjects had an intra-venous catheters placed. An electrocardiogram was also placed and monitored constantly. Body temperature was measured by ear thermometer every 10 min Venous blood was collected and cell-free plasma assayed for the presence of MMP-2 and MMP-9 using zymography and NO using HPLC assay for NO metabolites, nitrite and nitrate. Results: The administration of LPS resulted in increased body temperature and tachycardia. Time-dependent release of MMP-9(30 fold increase from the baseline) peaking at 2 h following infusion of LPS was observed. LPS did not signifi-cantly modify the activity of MMP-2 (P > 0.05). Infusion of LPS did not significantly change the levels of nitrite and nitrate (from 60 AE 11 to 67 AE 10 mM, P >0.05). Conclusion: The release of MMP-9, but not MMP-2 or NO, is a sensitive index of endotoxaemia in humans. MMP-9 release may contribute to the pathogenesis of sepsis via its pro-inflammatory effects on the vasculature.
Acta Anaesthesiologica Scandinavica 01/2003; 47:407-410. · 2.19 Impact Factor
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ABSTRACT: This review discusses the treatment of impaired gas exchange in acute respiratory distress syndrome (ARDS) using conventional ventilation, the open lung approach, prone position, nitric oxide (NO) inhalation and extracorporeal membrane oxygenation (ECMO). It is concluded that ventilation with high inspiratory pressures or volumes should be avoided, and that the open lung approach should be used as the first step. If this does not lead to satisfactory results, prone positioning is recommended, and if life-threatening hypoxemia persists, ECMO could be considered. NO inhalation is not recommended.
Lakartidningen 05/2000; 97(17):2058-63.
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ABSTRACT: Bleeding time has been reported to increase during gaseous nitric oxide (NO) inhalation in healthy volunteers and patients, and it has been speculated that inhaled NO inhibits platelet function. However, results have not been unanimous, and we have been unable to document any effects of inhaled NO on circulating platelets.
We performed a double-blind, placebo controlled cross-over study in which healthy volunteers (n = 15) inhaled NO (30 ppm, 30 min) or control gas. Aspirin (640 mg x 1 orally) was used as positive control on the third occasion (n = 14). Bleeding time was measured, and platelet function was determined flow cytometrically by measuring the expression of P-selectin on circulating platelets and locally activated platelets in wound blood. Skin perfusion close to the site for bleeding time incisions was assessed by laser Doppler flowmetry.
Bleeding time was unaffected by NO, as there were slight increases during both NO and control inhalation (+20% and +14% respectively, P = 0.9). Similarly, NO inhalation had no effect on platelet P-selectin expression in either systemic or wound blood, or on skin perfusion. Aspirin pretreatment, on the other hand, prolonged bleeding time (P < 0.001) and decreased P-selectin expression of platelets in wound blood (P = 0.03).
This first placebo-controlled study indicates that inhaled NO does not influence either bleeding time, platelet activity or skin perfusion. Thus, it is unlikely that treatment of critically ill patients with inhaled NO will aggravate haemostatic disturbances, which has previously been feared, by influencing platelet function.
European Journal of Clinical Investigation 11/1999; 29(11):953-9. · 3.02 Impact Factor
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ABSTRACT: To determine whether inhalation of nitric oxide (INO) can increase the frequency of reversal of acute lung injury (ALI) in nitric oxide (NO) responders.
Prospective, open, randomised, multicentre, parallel group phase III trial.
General ICUs in 43 university and regional hospitals in Europe.
Two hundred and sixty-eight adult patients with early ALI.
NO responders were patients whose PaO(2) increased by more than 20 % when receiving 0, 2, 10 and 40 ppm of INO for 10 min within 96 h of study entry. Responders were randomly allocated to conventional treatment with or without INO. INO, 1-40 ppm, was given at the lowest effective dose for up to 30 days or until an end point was reached. The primary end point was reversal of ALI. Clinical outcome parameters and safety were assessed in all patients.
Two hundred and sixty-eight patients were recruited, of which 180 were randomised NO responders. Frequency of reversal of ALI was no different in INO patients (61 %) and controls (54 %; p > 0.2). Development of severe respiratory failure was lower in the INO (2.2 % ) than controls (10.3 %; p < 0.05). The mortality at 30 days was 44 % for INO patients, 40 % for control patients (p > 0.2 vs INO) and 45 % in non-responders.
Improvement of oxygenation by INO did not increase the frequency of reversal of ALI. Use of inhaled NO in early ALI did not alter mortality although it did reduce the frequency of severe respiratory failure in patients developing severe hypoxaemia.
Intensive Care Medicine 10/1999; 25(9):911-9. · 5.40 Impact Factor
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ABSTRACT: Experimental models have indicated prothrombotic effects of inhibition of nitric oxide (NO) production, and anti-thrombotic effects of inhaled NO, but the influence of NO on platelet function in vivo in humans is not well established. We therefore investigated the effects of systemic inhibition of NO synthesis by N(G)-monomethyl-L-arginine (L-NMMA) and of NO inhalation on platelet function in vivo. On two occasions, L-NMMA (13.5 mg/kg) or saline infusion was administered to 14 healthy volunteers in a double-blind cross-over study. After a 30 min infusion of L-NMMA or placebo, NO inhalation (30 p.p.m) was added during the remaining 30 min of infusion, on both occasions. Measurements included filtragometry ex vivo (reflecting platelet aggregability), flow-cytometric evaluation of platelets in whole blood (fibrinogen binding and P-selectin expression), plasma beta-thromboglobulin (reflecting platelet secretion), cGMP in platelets and plasma, thrombin generation markers (thrombin fragment 1+2 and thrombin-antithrombin complexes) in plasma, and bleeding time. L-NMMA increased blood pressure and decreased heart rate. NO inhalation did not influence blood pressure or heart rate, but caused a 3-fold elevation in plasma cGMP levels (P<0.001). Neither L-NMMA nor NO influenced filtragometry readings or flow-cytometric determinations of platelet fibrinogen binding and P-selectin expression. Furthermore, plasma beta-thromboglobulin, platelet cGMP and thrombin generation markers were not influenced by either treatment. Bleeding time was not influenced by L-NMMA compared with placebo, but was increased by approximately 25% during NO inhalation (P<0.01), whether NO synthesis had been inhibited or not. The prolongation of bleeding time by inhaled NO was not accompanied by any effect on the platelet variables assessed. The present results indicate that circulating platelets are not influenced by endogenous or inhaled NO, presumably due to the rapid inactivation of NO in the blood. This does not exclude possible effects of endothelial NO in the interface between the blood and the vessel wall.
Clinical Science 09/1999; 97(3):345-53. · 4.61 Impact Factor
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ABSTRACT: Objective: To determine whether inhalation of nitric oxide (INO) can increase the frequency of reversal of acute lung injury (ALI)
in nitric oxide (NO) responders. Design: Prospective, open, randomised, multicentre, parallel group phase III trial. Setting: General ICUs in 43 university and regional hospitals in Europe. Patients: Two hundred and sixty-eight adult patients with early ALI. Interventions: NO responders were patients whose PaO2 increased by more than 20 % when receiving 0, 2, 10 and 40 ppm of INO for 10 min within 96 h of study entry. Responders were
randomly allocated to conventional treatment with or without INO. INO, 1–40 ppm, was given at the lowest effective dose for
up to 30 days or until an end point was reached. The primary end point was reversal of ALI. Clinical outcome parameters and
safety were assessed in all patients. Results: Two hundred and sixty-eight patients were recruited, of which 180 were randomised NO responders. Frequency of reversal of
ALI was no different in INO patients (61 %) and controls (54 %; p > 0.2). Development of severe respiratory failure was lower in the INO (2.2 % ) than controls (10.3 %; p < 0.05). The mortality at 30 days was 44 % for INO patients, 40 % for control patients (p > 0.2 vs INO) and 45 % in non-responders. Conclusions: Improvement of oxygenation by INO did not increase the frequency of reversal of ALI. Use of inhaled NO in early ALI did
not alter mortality although it did reduce the frequency of severe respiratory failure in patients developing severe hypoxaemia.
Intensive Care Medicine 08/1999; 25(9):911-919. · 5.40 Impact Factor
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ABSTRACT: Following an episode of acute respiratory distress syndrome (ARDS), some degree of measurable pulmonary impairment may be anticipated. ARDS is thought to be the more severe form of acute lung injury (ALI) and a recently proposed addition to conventional therapy in ALI/ARDS is inhaled nitric oxide (INO). We carried out a non-randomised follow-up study with pulmonary function tests on survivors of severe ALI/ARDS treated with INO.
Sixteen previously healthy pulmonary patients, survivors of severe ALI/ARDS, were evaluated with pulmonary function tests >8 months after the acute event. The tests included static and dynamic spirometry, diffusion capacity for carbon monoxide (DLCO), blood gas analysis and evaluation of a chest radiograph.
The most common abnormality seen was a low DLCO in 69% of the patients. Abnormally low values were seen in forced vital capacity in 31%, in forced expiratory volume in 1 s in 13%, and in residual volume and total lung capacity in 6%. Blood gas data were within normal limits in 15/16 patients. All chest radiographs showed resolution of the interstitial and alveolar changes present during the acute event.
In this non-randomised follow-up study we conclude that a degree of measurable pulmonary impairment after INO treatment in severe ALI/ARDS was common, but did not differ markedly from other published studies on pulmonary function in similar patient material. No late unexpected major abnormalities due to the inhaled nitric oxide treatment could be identified in these survivors.
Acta Anaesthesiologica Scandinavica 04/1998; 42(4):391-8. · 2.19 Impact Factor
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ABSTRACT: We hypothesized that the diversion of blood away from a hypoxic lung to the opposite oxygenated lung can be enhanced by inhaling nitric oxide (NO) into the oxygenated lung. We measured individual lung blood flow when 50 ppm NO was selectively inhaled to: a hyperoxic lung during contralateral hypoxia; a normoxic lung during bilateral normoxia; and a hyperoxic lung during bilateral hyperoxia. Twenty two patients with healthy lungs were studied during intravenous anaesthesia. The lungs were separately and synchronously ventilated. The relative perfusion of each lung was assessed by the inert gas elimination technique. Unilateral hypoxic (inspiratory oxygen fraction (FI,O2) 0.05) ventilation during contralateral hyperoxia reduced the perfusion of the hypoxic lung from a mean (SD) of 47 (9)% of cardiac output (Q'), to 30 (7)% (p<0.001) of Q'. NO inhalation to the hyperoxic lung increased its blood flow from 70 (7)% to 75 (6)% (p<0.05) of Q', and reduced the blood flow to the hypoxic lung to 25 (6)% (p<0.05). Unilateral NO inhalation during bilateral normoxia or hyperoxia had no effect on pulmonary blood flow distribution. Nitric oxide inhalation to a hyperoxic lung increases the perfusion to this lung by redistribution of blood flow if the opposite lung is hypoxic.
European Respiratory Journal 03/1998; 11(3):565-70. · 5.89 Impact Factor
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ABSTRACT: High amounts of endogenous nitric oxide (NO) have been demonstrated in the human upper airway, but the role of nasal NO is still unclear. The present study aims to describe nasal NO excretion in different animal species with special living conditions or anatomy.
Domestic animals (horse, cow, pig, sheep, dog, cat) and zoo-animals (Rhesus monkey, chimpanzee, gorilla, elephant, fur seal, alpaca, yak, dolphin, camel, capybara, bear, tiger, wolf, giraffe, alligator, Harris' hawk, kangaroo) were studied awake, resting or anaesthetised. NO concentrations were measured by chemiluminescence using different analysers and techniques, including measurements on mixed exhaled air, during continuous or intermittent gas sampling, and on single breaths.
Rhesus monkeys (number of individuals N = 5) and pigs (N = 2) were compared and displayed quite different excretion patterns. Allowing NO to accumulate in the nose during timed occlusions yielded peak concentrations in monkeys of 0.46 +/- 0.07 parts per million (ppm, mean +/- SEM), 0.59 +/- 0.08 ppm, 0.70 +/- 0.08 ppm and 1.02 +/- 0.05 ppm NO after 15, 30, 60 and 120 s of occlusion. In pigs, 0.012-0.021 ppm NO were recorded, independent of occlusion time. The chimpanzee was similar to the Rhesus monkey and the highest NO value, 2.9 ppm, was recorded after 4-5 min of occlusion. In single breaths from 3 elephants 0.031-0.082 ppm, from 1 gorilla 0.029 ppm, and from 1 chimpanzee 0.069 +/- 0.003 ppm NO (8 observations) were recorded.
We found considerable species difference in nasal NO excretion with pronounced amounts only in primates and elephants. The physiological implications of these findings remain to be defined.
Acta Anaesthesiologica Scandinavica 11/1997; 41(9):1133-41. · 2.19 Impact Factor
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O Luhr,
U Nathorst-Westfelt,
S Lundin,
C J Wickerts,
H Stiernström,
L Berggren,
S Aardal,
L A Johansson,
O Stenqvist,
U Rudberg,
A Lindh,
L Bindslev,
C R Martling,
V Hornbaek, C Frostell
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ABSTRACT: Patients with severe acute lung injury (ALI) have been treated compassionately on doctors' initiative with inhaled nitric oxide (INO) in Sweden and Norway since 1991. In 1994 the previously used technical grade nitric oxide was replaced by medical grade nitric oxide.
We have carried out a retrospective data collection on all identified adult patients treated with INO for >4 h during the period 1991-1994 focusing on safety aspects and patient outcome. We used the following exclusion criteria (1) Age <18 years, (2) Simultaneous treatment with extracorporeal removal of CO2 (3) NO inhalation period <4 h, (4) Incomplete or missing patient charts, (5) Use of INO in order to treat pulmonary hypertension following cardiac surgery, with little or no acute lung injury.
Inclusion criteria were met by 56 out of 73 identified patients. Mean age was 48+/-19 years and the median duration of INO treatment was 102 h. PaO2/FIO2 ratio at start of treatment was 85 +/- 33 mm Hg with a lung injury score (LIS) of 3.2+/-0.8. The aetiology of the lung injury was pneumonia (n= 27), sepsis (n=12) and trauma (n=8). Survival to hospital discharge was 41% and survival after 180 d was 38%. Three serious adverse events were identified, two from technical failures of the INO delivery device and one withdrawal reaction necessitating slow weaning from INO. No methaemoglobin values >5% were reported during treatment.
The overall mortality did not differ dramatically from historical controls with high mortality. Only a randomised study may determine whether INO as an adjunct to treatment alters the outcome in severe ALI. One cannot at present advocate the routine use of INO in patients with ALI outside such studies.
Acta Anaesthesiologica Scandinavica 11/1997; 41(10):1238-46. · 2.19 Impact Factor
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ABSTRACT: Concentrations of endogenous nitric oxide (NO) were measured in premature (n = 18) and term infants (n = 7). Nasal gas was aspirated continuously and after timed occlusions, 15 s and 60 s, by a fast-response chemiluminescence analyser. The sampling flow rate was 20 ml min-1. Typical NO recordings consisted of plateaux and postocclusive peaks. In term infants peak NO concentrations (60 s occlusion) were 2.71 +/- 0.44 parts per million (ppm) within 10 min after birth, increasing (p < 0.05) to 3.81 +/- 0.25 ppm at 4-7 d postnatally. Peak NO values (15 s occlusion) averaged 1.22 +/- 0.16 ppm in premature infants (postconceptional age 25-37 weeks, body weight 623-2844 g) and the NO concentrations increased significantly with postconceptional age (p < 0.05). Nasal excretion rate, estimated from plateau NO concentrations and sampling flow rate, was 0.10 +/- 0.01 nmol min-1 kg-1 in both groups. We conclude that premature and term newborn infants excrete considerable amounts of NO in the upper airways, with hitherto not fully known functions.
Acta Paediatrica 11/1997; 86(11):1229-35. · 2.07 Impact Factor
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ABSTRACT: Short-term infusion of NG-monomethyl-L-arginine (L-NMMA) reversibly inhibits endogenous nitric oxide (NO) production in humans. We studied responses to more long-lasting (60 min) infusions, at doses high enough to cause effective inhibition of endogenous NO.
Eight healthy volunteers had catheters (pulmonary, arterial and venous) placed. Measurements included hemodynamics, endogenous NO levels in nasal air, bleeding time, and cyclic guanosine monophosphate (cGMP) and catecholamines in plasma. L-NMMA was infused at 0.3 mg.kg-1.min-1 during 30 min, followed by 0.15 (n = 6) or 0.3 (n = 2) mg.kg-1.min-1 during 30 min.
L-NMMA significantly elevated mean arterial pressure by 12 +/- 3%, due to an increase in systemic vascular resistance. Cardiac output decreased by 23 +/- 3%, due to a decrease in stroke volume. Pulmonary vascular resistance (P < 0.05) increased, but mean pulmonary arterial pressure was stable. Forearm vascular resistance (P < 0.05) decreased. Bleeding time was shortened by 31 +/- 4% (P < 0.01). L-NMMA infusion reduced NO concentrations in nasal air by 64 +/- 2% (P < 0.01). Arterial pressure remained elevated and nasal NO remained depressed 90 min after the infusion, whereas most other responses were reversed at that time. Plasma cGMP showed only minor changes. Plasma norepinephrine decreased, suggesting reflexogenic inhibition of sympathetic activity, whereas epinephrine levels were low and stable throughout the experiment.
Dosage of (13.5 mg.kg-1 in 60 min) L-NMMA infusion in humans was well tolerated. Pronounced and long-lasting inhibition of endogenous NO production, as evidenced by measurements in nasal air, resulted in unevenly distributed vasoconstriction, a transient decrease in cardiac output, and reflexogenic sympathetic withdrawal. Furthermore, bleeding time was shortened, suggesting platelet activation.
Acta Anaesthesiologica Scandinavica 10/1997; 41(9):1104-13. · 2.19 Impact Factor
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Acta Physiologica Scandinavica 05/1997; 159(4):345-6. · 2.55 Impact Factor
