Mother-infant interactions during fetal and neonatal life with special reference to atopy.
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Animals↗
Biomedical subjects
S Lundin
Publications and source records attributed to S Lundin.
A study of mixing conditions during nitric oxide administration using simultaneous fast response chemiluminescence and capnography.
We have evaluated the mixing properties of nitric oxide in inspired gases for five different administration techniques. Nitric oxide and carbon dioxide were delivered to the ventilator system before the ventilator or after the ventilator as a continuous flow, either directly into the inspiratory limb or into a mixing chamber positioned in the inspiratory limb. Both gases were delivered as above but synchronized with inspiration. Mixing conditions were evaluated using fast response chemiluminescence for nitric oxide and capnography for carbon dioxide analysis. Administration of nitric oxide and carbon dioxide directly into the inspiratory limb as a continuous flow or with a magnetic valve-controlled synchronized flow resulted in peak concentrations of 236% and 220%, respectively, of expected values. The use of a mixing chamber reduced these values to 104% and 102%, respectively. Administration of nitric oxide as a continuous flow into the tubing of an intermittent flow ventilator resulted in highly fluctuating inspiratory peak concentrations, which could be avoided with a mixing chamber.
Capnography↗
A retrospective analysis of nitric oxide inhalation in patients with severe acute lung injury in Sweden and Norway 1991-1994.
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
Administration, Inhalation↗
Nitric oxide administration after the ventilator: evaluation of mixing conditions.
BACKGROUND: Because of the potential toxicity of nitric oxide (NO) and its oxidising product nitrogen dioxide (NO2), any system for the delivery of inhaled NO must aim at stable and predictable levels of NO and as low concentrations as possible of NO2. METHODS: In a laboratory set-up, we have evaluated mixing conditions in a system where NO is added after the ventilator with continuous flow. Mixing was studied by using carbon dioxide (CO2) as a tracer gas since capnography has a short response time (360 ms) in comparison with measurements of NO with electrochemical fuel cells (response time of 18 s). CO2 (in volumes corresponding to an ideal mixture of 1, 3 and 6%) was fed, after the ventilator, either into plain breathing tubing, into one or two soda lime absorbers, or into an empty and a soda lime-filled canister, at different ventilatory rates and different I:E ratios. Samples were drawn from the inspiratory limb close to the Y-piece. NO was added in the same way and in the same volume as the highest concentration of CO2. RESULTS: CO2 added to plain tubing resulted in peak levels up to five times the set levels, while addition to a mixing box with an empty and a soda lime-filled canister resulted in even mixing with gas concentrations close to the ideal. When NO was fed into plain tubing, low levels were measured at the Y-piece, indicating poor mixing. Gas supply to a mixing chamber resulted in even concentrations. CONCLUSION: Even and predictable levels of NO can be obtained with continuous flow of NO to the inspiratory limb, after the ventilator, if a mixing chamber is used. To obtain adequate mixing, the volume of the mixing box should be greater than the tidal volume.
Carbon Dioxide↗
Effects of dopamine, dopexamine and dobutamine on renal excretory function during experimental sepsis in conscious rats.
BACKGROUND: Acute renal failure is a frequent complication in human sepsis. Various inotropic drugs are often used to improve central haemodynamics and renal function. The differential preservative role of the most commonly used inotropic drugs on renal function, in this condition, has previously not been extensively studied. The aim of this experimental animal study was therefore to compare the preserving effects of dopamine, dopexamine, dobutamine and saline on renal excretory function, after induction of sepsis in conscious rats. METHOD: The effects of dopamine (DA) (2.5 micrograms.kg-1.min-1; n = 11), dopexamine (DX) (1 microgram.kg-1.min-1; n = 10), dobutamine (DB) (5 micrograms.kg-1.min-1; n = 10) and saline (n = 13) on the glomerular filtration rate (GFR), urine flow (UF), sodium excretion (SE) and fractional urinary excretion of sodium (FUENa) were studied and compared in conscious rats subjected to a 1-h infusion of live E. coli bacteria (10(9)/h). RESULTS: In the saline-treated control group, bacteria infusion decreased GFR, UF, SE and FUENa by 31%, 53%, 51% and 36% respectively, associated with a 16% decrease in mean arterial pressure (MAP), and a 10% increase in heart rate (HR). In the post-E. coli treatment period, the fall in MAP was less pronounced with DX compared to both DB and control, while there was no difference between DX and DA. The increase in HR was most pronounced with DB. GFR decreased to a lesser extent with DX compared to DA, DB and control. UF and SE were better maintained with DX compared to DB and control, while there was no difference in FUENa between the groups. CONCLUSION: We conclude that dopexamine, to a greater extent than dopamine and dobutamine, improves renal excretory function in experimental septic shock.
Adrenergic beta-Agonists↗
Uptake of inhaled nitric oxide in acute lung injury.
BACKGROUND: Despite the widespread use of inhaled nitric oxide (NO), little is known of its pulmonary uptake in patients with acute respiratory failure. METHODS: Fourteen patients with acute lung injury (ALI) and ongoing NO therapy were studied. Three doses of NO (5, 10 and 40 ppm) were given for 20 min and at each dose level the following parameters were recorded: minute ventilation, inspiratory NO conc., mixed expired NO conc., end-tidal NO conc., mixed expired CO2 conc., end-tidal CO2 conc, and arterial CO2 tension. Total uptake was calculated and correlated to the total amount of NO inhaled, the amount of NO administered to the alveolar space, and the amount of NO administered to the perfused alveolar space. RESULTS: About 35% of the total amount of NO delivered is taken up by the lungs, 70% of NO administered to the alveolar space is taken up, and 95-100% of the NO administered to perfused alveolar space is taken up. The size of the alveolar dead space varied between 10 and 60% of the alveolar space. At 40 ppm of inhaled NO there was no difference between inspired and mixed expired NO2 concentration, indicating that there is no significant NO2 formation taking place in the lungs during NO inhalation at the concentrations studied. CONCLUSIONS: Practically all NO administered to the perfused alveolar space is taken up. The total uptake differs from that of healthy persons probably because of differences in the alveolar dead space.
Administration, Inhalation↗
Early determinants of immunocompetence.
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Antibody Formation↗
Reduced airway absorption in seasonal allergic rhinitis.
The common notion that increased mucosal absorption characterizes allergic and inflamed airways is poorly supported by physiologic in vivo data. We have now examined whether the airway mucosa of patients with seasonal allergic rhinitis develop a change in absorption during their active disease period. Twelve patients with birch pollen rhinitis were examined twice, prior to and late into a Swedish birch pollen season. Ten healthy subjects were examined once. A nasal pool device was used to fill the unilateral nasal cavity with fluid containing 1-deamino-8-D-arginine vasopressin (desmopressin, 20 micrograms/ml) as absorption tracer. The peptide tracer solution was removed after 15 min, and absorption was determined by analysis of the peptide in the 24-h urine sample. Nasal absorption did not differ between healthy subjects and symptom-free patients outside the season. After 3 wk of symptom-producing seasonal allergic rhinitis, absorption of the peptide across the nasal mucosa was less (p < 0.05) than outside the season. These data indicate that hyperresponsiveness and disease progression in seasonal allergic rhinitis are not due to a compromise of the mucosal barrier that would permit increased absorption of mucosally deposited solutes. The reduced absorption may in part reflect the ability of the airway epithelium in vivo to maintain and potentially improve its barrier function by efficient epithelial restitution processes.
Absorption↗
Iatrogenic [corrected] extrapontine myelinolysis in central diabetes insipidus: are cyclosporine and 1-desamino-8-D-arginine vasopressin harmful in association?
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Bone Marrow Transplantation↗
Intestinal inflammation and barrier function in HLA-B27/beta 2-microglobulin transgenic rats.
BACKGROUND: Since intestinal inflammation is correlated with impaired barrier functions, transgenic HLA-B27/human beta 2-microglobulin rats that spontaneously develop intestinal inflammation were used to investigate whether onset of inflammation or impaired barrier function was the initial event. METHODS: During the age period of 9-14 weeks, transgenic and non-transgenic (control) rats were gavaged weekly with the marker molecules, 51Cr-ethylenediaminetetraacetic acid, 1-deamino-8-D-arginine vasopressin, and albumin, which were quantified in blood or urine. RESULTS: At 12 weeks of age the first signs of inflammation appeared with decreased body weight gain, decreased urine production, and onset of diarrhea. By 14-15 weeks of age all transgenic rats had developed intestinal inflammation, as confirmed by histology and increased myeloperoxidase content, whereas no inflammation was observed in controls. Intestinal passage of the markers did, however, not differ between transgenic and control rats over the studied period. CONCLUSIONS: The results suggest that intestinal inflammation precedes altered intestinal barrier function in this inflammation model.
Animals↗
Enhancing effects of monohexanoin and two other medium-chain glyceride vehicles on intestinal absorption of desmopressin (dDAVP).
The intestinal absorption enhancement of the nonapeptide [Mpa1,D-Arg8]vasopressin (dDAVP) by medium-chain glyceride vehicles was studied using an in vivo rat model. Rats were gavaged with dDAVP formulated with three different lipid vehicles: (1) monohexanoin, (2) mixed monoglycerides, diglycerides and triglycerides of hexanoic acid and (3) monoglycerides, diglycerides and triglycerides of octanoic and decanoic acids, and with saline as control. The marker absorption into blood and urine was followed for 24 hr. All lipid vehicles enhanced the oral bioavailability of dDAVP, but monohexanoin gave the highest increase, approximately 10 times that of control. In contrast to dDAVP, the stable and more lipophilic nonapeptide analog [Mpa1,D-Tyr(ethyl)2,Val4,D-Arg8]oxytocin did not show increased urine recovery when formulated with monohexanoin. A 2-fold increase in urine recovery of the inert low-molecular-weight marker [51Cr]EDTA was observed when formulated with monohexanoin. With use of the fluorescent marker Evans blue formulated with monohexanoin, an elevated accumulation of Evans blue in the mucus layer was observed after incubation in in situ loops. No mucosal damage after lipid vehicle gavage was observed by light microscopic evaluation. Medium-chain glycerides functioned well as oral absorption enhancers of the model peptide dDAVP, and monohexanoin showed the highest enhancement capacity. The mechanisms of this enhancement appear to be related to a protection against luminal dDAVP degradation, mucoadhesive properties of the vehicle and, possibly, an altered epithelial absorption pathway.
Animals↗
Metabolism of vasopressin, oxytocin and their analogues [Mpa1, D-Arg8]-vasopressin (dDAVP) and [Mpa1, D-Tyr(Et)2, Thr4, Orn8]-oxytocin (antocin) in human kidney and liver homogenates.
Information regarding the metabolic fate of the neurohypophyseal hormones arginine-vasopressin (AVP), oxytocin (OT) and their analogues in man is practically non-existent. The aim of the present study was to investigate the stability of oxytocin, vasopressin and their analogues dDAVP and [Mpa1-D-Tyr2(Et), Thr4, Orn8]-oxytocin (antocin) in human renal microvilli brush border membranes and in human liver membranes. After incubation the extent of degradation of the peptides was determined by reversed phase high-performance liquid chromatography (HPLC). The degradation of both AVP and OT was rapid in the presence of glutathione and human renal microvilli membranes. AVP, as well as dDAVP, was stable when incubated with microvilli membranes without glutathione, while OT was metabolized. The metabolization of the oxytocin analogue, antocin, also varied with the presence of glutathione. While in the absence of glutathione a more lipophilic peak eluted, a more hydrophilic peak was observed with glutathione on HPLC. The lipophilic peak was found to coelute with the truncated analogue [Mpa1, D-Tyr2 (Et), Thr4, desOrn8, Gly9]-oxytocin. No degradation occurred when the peptides were incubated with liver membranes. However, when using crude, unpurified liver homogenate degradation occurred for all peptides except antocin. The degradation of AVP in the human unpurified liver homogenate was as rapid as in the renal microvilli membranes. Similarly, OT was more rapidly degraded in human kidney microvilli membranes in the presence of glutathione than in the human crude liver homogenate, when using equal amounts of protein in the incubations. Thus, the present investigation indicates the existence of two possible metabolic pathways, in kidney microvilli, one for OT, which did not require the presence of reduced glutathione, and one for AVP, which required the presence of reduced glutathione. Liver degradation, on the other hand, requires the hepatocytes.
Arginine Vasopressin↗
Response to nitric oxide inhalation in early acute lung injury.
OBJECTIVE: To evaluate the dose response of inhaled nitric oxide (NO) on gas exchange and central haemodynamics in patients with early acute lung injury (ALI). DESIGN: Prospective, multicentre clinical study. SETTING: General ICUs in university and regional hospitals. PATIENTS: 18 Patients with early ALI according to specified criteria. INTERVENTIONS: During controlled ventilation an inhalation system was used to deliver NO (1000 ppm in N2) and O2/air to the low pressure fresh gas inlet of a Siemens 900C ventilator. Haemodynamics and pulmonary gas exchange variables were measured at baseline and at stepwise increased inspiratory NO concentrations of 0.1, 0.3, 1, 3, 10, 30 and 100 ppm, each dose being maintained for 15 min. Dose testing was repeated the next day, and the response to prolonged (2 h) NO inhalation at 1 and 10 ppm was also tested. MEASUREMENTS AND RESULTS: Inhalation of NO produced a significant increase in PaO2 (P < 0.0025). The degree of response, as well as the optimal NO dose varied in individual patients and between different days. Venous admixture (QVA/QT) was reduced (P < 0.02) from 38% (31-46%) to 33% (26-41%). In our patients with early acute lung injury and only a moderate elevation in pulmonary arterial pressure NO inhalation did not reduce mean pulmonary artery pressure significantly, being 27.0 (21-30) mmHg at baseline and 26.0 (21-30) mm Hg at 100 ppm. CONCLUSIONS: This study shows that improvements in arterial oxygenation in response to inhaled NO may show great inter- as well as intraindividual variability, and that improvements in arterial oxygenation occur without any measurable lowering of the pulmonary artery pressure.
Administration, Inhalation↗
Effects of atrial natriuretic peptide on acute renal impairment in patients with heart failure after cardiac surgery.
OBJECTIVE: To investigate the effects of IV infusion of atrial natriuretic peptide (human ANP 1-28) on renal function in patients with acute heart failure and renal impairment after cardiac surgery. DESIGN: Pharmocodynamic dose-effect investigation. SETTING: Cardiothoracic Intensive Care Unit of a university hospital. PATIENTS: Twelve patients (mean age 68 years, range 44-78 years) treated with inotropic drugs and an intra-aortic balloon pump (n = 8) were studied 1-3 days after cardiac surgery. Patients had acute renal impairment, defined as a rise in serum creatinine of more than 50% compared to preoperative values. Patients were receiving dopamine and furosemide infusion to increase urine flow. INTERVENTIONS: Baseline measurements of glomerular filtration rate (GFR) and renal blood flow (51Cr-EDTA and PAH clearance) were first performed during two 30-min periods. ANP was then administered for two consecutive 30-min periods (25 and 50 ng/kg per min), followed by two control periods. MEASUREMENTS AND MAIN RESULTS: Mean arterial pressure decreased by 6% at the highest ANP dose. Urine flow, GFR and RBF increased 62%, 43% and 38%, respectively, while renal vascular resistance decreased 30%. At this dose level, circulating ANP concentrations were on the average eight fold higher than preinfusion levels. CONCLUSIONS: ANP improved renal function and decreased elevated renal vascular resistance in patients with renal dysfunction after cardiac surgery. The improvement in renal blood flow and glomerular filtration rate may be of potential therapeutic value to prevent or treat exaggerated renal vasoconstriction in patients with acute renal impairment following cardiac surgery.
Acute Kidney Injury↗
Passive drug diffusion via standardized skin mini-erosion; methodological aspects and clinical findings with new device.
PURPOSE: To develop a clinical alternative to drug administration by injection or infusion. METHODS: A simple, mechanical device (Cellpatch) enables both the formation of a standardized small epidermal bleb and exposure of the circular base of the bleb to drug. The epidermis is split off by suctioning without bleeding or discomfort in a layer superficial to dermal capillaries and nociceptor nerves. Transdermal invasivity is thus avoided. Absorption of dextran test drug in aqueous solution vs molecular weight (3 kDa-70 kDa) and erosion area (3 kDa, diameter: 3-10 mm) were studied in healthy volunteers. The feasibility of using Morphine cellpatch (cell filled with 20 mg/ml morphine hydrochloride, aqueous solution, erosion diameter 6 mm) for post-operative pain relief was studied in two different patient groups; the Cellpatch was removed after 48 hours. Plasma morphine concentrations were determined at intervals. RESULTS: Dextrans of all sizes were efficiently absorbed transdermally, although absorption decreased with increasing molecular weight. The degree of absorption was directly related to the area of the mini-erosion. There were no sign of dose-dumping even with the largest erosions. The Cellpatch performed well in the demanding conditions of the postoperative unit, and was considered easy to use. Pharmacokinetically, the postoperative morphine delivery was related to that of a continuous infusion, with variability and dose in the same range as a continuous morphine infusion used clinically for providing basal pain relief. There were no bacterial growth in the morphine cells at 48 h. Reepithelialization of the erosion was rapid. CONCLUSIONS: The feasibility of administering drugs in a wide size range by passive diffusion through a standardized skin mini-erosion was demonstrated; the rate of absorption decreased with increasing molecular weight. The small area of the erosion restricts and controls the concentration driven diffusion of drug into the circulation. As a consequence of the favorable findings, three placebo-controlled clinical studies using Morphine cellpatch for postoperative pain relief are currently underway.
Administration, Cutaneous↗
Release of prolactin as well as adrenocorticotropin after administration of arginine-vasopressin to healthy men.
The study was undertaken to obtain simultaneous measurements of circulating anterior pituitary hormone levels after the i.v. injection of arginine-vasopressin (AVP). Nine healthy men, mean age 31 years (range 24-41), received single blind with at least one week apart, after resting in the supine position for 30 min, AVP 0.26 microgram/kg body weight i.v. (Pitressin, Parke-Davis) or saline in randomized order. Blood samples were taken at 0, 10, 20, 30, 45 and 60 min for analyses of serum or plasma levels of ACTH, prolactin, TSH, GH, FSH, LH and AVP. The hormone responses after AVP or saline were calculated as the area under the curve (AUC) 0-60 min as well as the change in hormone levels from 0 to 10 min to pick up possible short lasting effects when there was no significant difference in AUC between AVP and control. As expected the highest plasma concentration of AVP was measured 10 min after the injection of AVP and well comparable to those in other studies where AVP was observed to release ACTH. The AUC:s for both ACTH and prolactin levels were significantly increased after AVP in comparison with saline (p = 0.008 and p = 0.038, respectively). The AUC:s for the other hormones measured were not significantly changed after AVP, but there were small but significant changes in the 0-10 min values for TSH and LH after AVP compared to saline. It is concluded that AVP has the potency to release not only ACTH but also prolactin in healthy men.
Adrenocorticotropic Hormone↗
Myocardial circulatory and metabolic effects of atrial natriuretic peptide after coronary artery bypass grafting.
The purpose of this study was to examine the effects of incremental infusion rates of human atrial natriuretic peptide (ANP), 25, 50, 100 ng.kg-1. min-1, on myocardial blood flow and metabolism (n = 10), and to compare the effects of ANP on these variables with those of equipotent infusion rates of sodium nitroprusside (SNP) (n = 9) 1-3 h after coronary artery bypass grafting (CABG). ANP induced a dose-dependent decrease in mean arterial blood pressure and systemic vascular resistance. There were no changes in cardiac index, heart rate, or cardiac filling pressures. ANP caused no changes in myocardial blood flow or its distribution, and caused no changes in myocardial oxygen extraction. Regional myocardial lactate uptake (RMLU) and extraction (RMLE) increased significantly (P < 0.05) at 50 ng.kg-1.min-1 (10.2 +/- 3.8 mumol/min and 8.2% +/- 3.0%, respectively) as compared to control (-1.1 +/- 3.0 mumol/min and -1.3% +/- 3.3%, respectively). RMLE and RMLU were significantly (P < 0.05) higher with ANP (5.7% +/- 2.5% and 6.8 +/- 3.7 mumol/min, respectively) compared to SNP (-1.5% +/- 2.1% and -0.1 +/- 3.7 mumol/min, respectively). We conclude that ANP has no dilatory effects on coronary vascular resistance vessels and thus lacks the potential to maldistribute flow, and that ANP improves myocardial lactate metabolism after CABG.
Atrial Natriuretic Factor↗
Safety aspects of delivery and monitoring of nitric oxide during mechanical ventilation.
In the presence of oxygen NO is oxidised to NO2, which is toxic in higher concentrations. In this technical investigation, we evaluated a dosage system, modified from Stenqvist et al. 1993 (1), regarding NO and NO2 levels. NO was administered before the ventilator and NO2 scavenged using a soda little absorber in the inspiratory limb close to the ventilator. NO/NO2 levels were measured using fuel cell technique. We tested the duration of soda lime scavenging, put in additional soda lime absorbers, used charcoal as absorber and exchanged tubing material. NO was delivered after the ventilator and we studied effect of interruption of ventilation. With concentrations of NO at or below 40 parts per million (ppm) at F1O2 0.9, NO2 levels were 1.2 ppm or lower. Corresponding values for 20 and 10 ppm were 0.4 and 0.2 ppm, respectively. Duration of the soda lime absorber was at least 72 hours. Additional soda lime absorbers did not further reduce NO2 levels. Charcoal absorbers reduced NO2, but also NO by 45% from set value. Tubing materials had no influence on NO and NO2 levels. When administering NO at the Y-piece, levels of NO were increased by 35-60% and NO2 levels by 110-230% compared to set values. Oxidation of NO to NO2 is continuously taking place in the breathing system. Doses of up to 40 ppm NO should be considered safe regarding NO2 levels. Administration of NO at the Y-piece gives high and unpredictable levels of NO2.
Absorption↗