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Biomedical subjects

S Lundin

Publications and source records attributed to S Lundin.

At least 37 records · Page 2Linked to original sources

Direct tracheal airway pressure measurements are essential for safe and accurate dynamic monitoring of respiratory mechanics. A laboratory study.

BACKGROUND: All monitoring of respiratory mechanics should depend on tracheal pressures (Trach-P) as endotracheal tube resistance (ETT-Res) will otherwise distort them. The aim of this study was to investigate factors that may vary ETT-Res, causing difficulties in ETT-Res estimation clinically, and to evaluate a method for direct Trach-P measurements to obviate these problems. METHODS: In a model we studied: 1) The influence on ETT-Res caused by different connectors and secretions; 2) Direct Trach-P measurements with a catheter (o.d. 2 mm, i.d. 0.9 mm) with either end or side hole, filled with either air or liquid, introduced through the ETT lumen and evaluated regarding response time and position. RESULTS: The pressure drop between trachea and Y-piece increased by 15% when respectively a swivel connector and a humidification device were connected to the ETT. When injecting 1 ml and 2 ml gel into the ETT lumen the inspiratory resistance increased 100% and 600% respectively. The response time of all catheters was < or = 12 ms. During constant flow in inspiratory and expiratory directions the pressure difference between an end hole catheter positioned from 2 cm above the ETT tip to 4 cm below and a reference pressure in the artificial trachea was less than 1.5 cmH2O. CONCLUSIONS: ETT connections and secretions cause a variance in resistance. Tracheal pressure can be measured with high precision with an air- or liquid-filled catheter. An end hole catheter placed within 2 cm above or below the ETT tip will give sufficiently precise measurements for clinical purposes.

Air Pressure↗

Descending aortic blood flow and cardiac output: a clinical and experimental study of continuous oesophageal echo-Doppler flowmetry.

BACKGROUND: Several studies have demonstrated that perioperative optimisation of oxygen delivery and haemodynamics can reduce mortality and morbidity for high-risk surgical patients. To optimise cardiac output, reliable, continuous and "less invasive" methods for measuring cardiac output are urgently needed. METHODS: Eight landrace pigs were studied during experimental repeated cardiac tamponade and 14 patients during liver transplantation. Aortic blood flow was measured by using transoesophageal echo-Doppler technique. A total of 91 paired measurements of aortic blood flow and cardiac output with different techniques were performed in the pigs and 124 paired measurements in the patients. RESULTS: Transoesophageal echo-Doppler did provide continuous real-time monitoring of the rapid and dramatic haemodynamic changes occurring during cardiac tamponade and during liver transplantation, while only intermittent information was obtained from the bolus thermodilution technique. Changes in haemodynamics were more difficult to detect with the "continual" cardiac output thermodilution technique. Changes in aortic blood flow closely followed changes in cardiac output determined by the bolus thermodilution technique both in pigs (r= 0.89) and in patients (r=0.80). In patients, aortic blood flow constituted about 70% of cardiac output determined by the bolus thermodilution technique. CONCLUSIONS: A combined echo-Doppler technique can be valuable for continuous monitoring of haemodynamic changes in the perioperative setting, and changes in aortic blood flow agree well with corresponding changes in cardiac output intermittently obtained by thermodilution cardiac output measurements. With the combined echo-Doppler technique a proper position of the Doppler beam is greatly facilitated by the M-mode echo visualisation of the aortic wall and aortic cross-sectional area is continuously measured.

Adult↗

[Patients' attitudes to xenotransplantation: "I'll do anything, I don't want to die!"].

Transplantation of neural tissue is an effective therapeutical approach in Parkinson's disease, but the method is constrained by the lack of suitable donor material. Embryonic neural tissue from pigs, xenografts, is considered as an alternative source of donor tissue. The attitudes towards neural tissue grafting in general and xenografts in particular were investigated by interviewing a group of patients with Parkinson's disease. The analysis revealed an ambivalence regarding xenografts. A pragmatic view, with priority placed on survival over ethical and other reservations, became apparent.

Animals↗

Clinical aspects and perspectives in islet xenotransplantation.

In 1990-1993, eight diabetic renal transplant patients had porcine fetal islets injected intraportally at Huddinge Hospital in Stockholm. Four of the patients had evidence of xenograft function reflected in the excretion of small amounts of porcine C-peptide. Two patients had the porcine fetal islets placed under the capsule of a simultaneously transplanted kidney. In one of these patients, a graft biopsy specimen taken 3 weeks after transplantation revealed morphologically intact epithelial cells staining positively for insulin and glucagon. The insulin production was in all instances insufficient to affect the patient's insulin requirements. All patients formed specific xenoantibodies (mostly anti-Gal); presumably, most of the xenoislets were destroyed by rejection. On follow-up studies carried out 6-8 years after xenotransplantation, most patients still had higher-than-pretransplant levels of xenoantibodies. There was no evidence of transmission of porcine endogeneous retroviruses to the patients. All patients expressed a positive attitude toward the use of animal tissue for treatment of disease, and none of the patients regretted participating in the trial. Cell transplantation is leading the way at present for clinical xenotransplantation. The finding that complement inhibition protects intraportally injected porcine islets from an injurious incompatibility reaction holds promise for future clinical application. A similar protective effect might be achievable with the use of islets from transgenic pigs expressing human complement receptors.

Animals↗

Evaluation of pressure/volume loops based on intratracheal pressure measurements during dynamic conditions.

BACKGROUND: The aim of this study was to evaluate and compare information about lung mechanics obtained by dynamic pressure/volume loops based on Y-piece and intratracheal airway pressure. METHODS: Airway pressure was measured simultaneously at the Y-piece and trachea. Flow/tidal volume was measured by sidestream spirometry at the Y-piece. The effect of an intraluminal catheter in the tube was evaluated in a lung model. Ten adults with acute lung injury and mechanical ventilation were studied. Measurements were performed during volume-(VC) and pressure-controlled (PC) ventilation at different ventilator settings. RESULTS: Lung model: There was a statistically significant difference (P<0.001) between trachea and Y-piece pressure/volume loop areas during both VC and PC ventilation. The ratio trachea area/Y-piece area decreased with increased endotracheal tube resistance (r=0.96). PATIENTS: The difference between trachea and Y-piece P/V-loops was statistically significant at all 21 ventilatory settings (P<0.05-0.001). The tracheal loop revealed clearly intrinsic PEEP and lowered compliance during overinflation, which was difficult or impossible to see in the Y-piece pressure/volume loop. CONCLUSION: By measuring airway pressure at the trachea the effect of endotracheal tube resistance during inspiration is excluded while it is included during expiration, yielding correct end-points of inspiration and expiration. This makes it possible to calculate accurately total compliance of the respiratory system during dynamic conditions. By monitoring of airway pressure in the trachea, respiratory mechanics can be assessed more accurately and ventilatory settings adjusted to attenuate ventilator induced lung injury.

Aged↗

A new method for non-invasive, manoeuvre-free determination of "static" pressure-volume curves during dynamic/therapeutic mechanical ventilation.

BACKGROUND: Lung mechanics are usually measured using static or quasistatic methods, abandoning normal ventilatory treatment. We have developed a method to calculate the alveolar pressure during dynamic/therapeutic conditions, "the dynostatic pressure" (P(dyn)), using airway pressure (P) measured in the trachea and volume (V) and flow (V) at the Y-piece. METHODS: P(dyn) is calculated according to the formula P(dyn)= (P(insp) x V(exp)-P(exp) x V(insp))/(V(exp)-V(insp)), making the assumption that inspiratory and expiratory resistances are equal at isovolume. The method was evaluated in a lung model during dynamic conditions comparing measured alveolar pressure (P(alv)) and P(dyn) at equal and unequal inspiratory and expiratory resistances and P/V-curves obtained during static and dynamic conditions. The algorithm was then applied in patients with acute lung injury (ALI). RESULTS: When inspiratory and expiratory resistances were equal there was an excellent agreement between the P(dyn) and the P(alv), irrespective of ventilator settings, r(2)=0.995 (range 0.981-0.999). P(dyn) derived compliance was equal to static values. When the ratio between inspiratory and expiratory resistance was varied between 2.3:1 and 1:2.3 the r(2) was above 0.95 (range 0.952-0.996). Development of intrinsic PEEP and overdistension was easily revealed in patients, as shown by the dynostatic P/V-curve. CONCLUSION: The dynostatic method gives a breath-by-breath reflection of the interaction between ventilatory settings and lung mechanics in patients during ordinary ventilator treatment. It is only marginally affected by the moderate differences in inspiratory versus expiratory resistances present in patients with ALI.

Airway Resistance↗

Inhalation of nitric oxide in acute lung injury: results of a European multicentre study. The European Study Group of Inhaled Nitric Oxide.

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 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. 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.

Administration, Inhalation↗

An IL-2-toxin, DAB389IL-2, inhibits delayed-type hypersensitivity but enhances IgE antibody production.

BACKGROUND: Expression of high-affinity IL-2 receptor (IL-2R) on T lymphocytes, key cells in chronic inflammation, is a T-cell activation marker. OBJECTIVE: We sought to evaluate the effect of the fusion protein DAB389IL-2, which kills cells bearing IL-2R, on delayed-type hypersensitivity and antibody production in Brown Norway rats sensitized with trimellitic anhydride (TMA). METHODS: DAB389IL-2 (25 micrograms/kg/day) or placebo was administered intraperitoneally for 8 days over the period of sensitization, starting 2 days before sensitization. RESULTS: The administration of DAB389IL-2 resulted in a one-third reduction in the number of IL-2R-bearing cells and significant weight loss of animals. Delayed-type hypersensitivity, evaluated at 5 weeks after sensitization, was significantly inhibited by treatment with DAB389IL-2. In contrast, production of IgE anti-TMA antibodies after sensitization was increased by treatment with DAB389IL-2. DAB389IL-2 affected neither IgG anti-TMA antibody nor total IgE levels. CONCLUSION: These data imply that systemic administration of DAB389IL-2 in Brown Norway rats influences cells that have regulatory effects on the immune system, resulting in a switch from a TH1 to a TH2 type of immune response.

Allergens↗

Indirect-response modeling of desmopressin at different levels of hydration.

The objective of the present study was to investigate the pharmacokinetics (PK) and pharmacodynamics (PD) of desmopressin in healthy male subjects at different levels of overhydration. Also, we examined if an indirect-response model could be related to renal physiology and the pharmacological action of desmopressin. Eight healthy male subjects participated in this open, randomized crossover study with three periods. Each subject was orally water loaded (0 to 20 ml.kg-1 body weight) on 3 study days in order to achieve three different levels of hydration. After the initial water load, urine was voided every 15 min and the volumes were measured. To ensure continuous overhydration the subjects replaced their fluid loss with drinking-water. When a steady-state diuresis was achieved after approximately 2 hr, 0.396 microgram of desmopressin was administered intravenously as a bolus injection. Blood was sampled and urine was collected at intervals throughout the study day (10 hr). An indirect-response model, where desmopressin was assumed to inhibit the elimination of response, was fit to the urine osmolarity data. There were no statistically significant effects of different levels of hydration, as expressed by urine flow rate at baseline, on the estimates of the PK and PD model parameters. The calculated terminal half-lives of elimination (t1/2 beta) ranged between 2.76 and 8.37 hr with an overall mean of 4.36 hr. The overall means of plasma clearance and the volumes of distribution of the central compartment (Vc) and at steady state (Vss) were estimated to be 1.34 (SD 0.35) ml.min-1.kg-1, 151 (SD28) ml.kg-1, and 386 (SD 63) ml.kg-1, respectively. High urine flow rate, indicating overhydration, produced a diluted urine and thus a low osmolarity at baseline (R0). The effect of the urine flow rate on the urine osmolarity at baseline was highly significant (p < 0.0001). The mean values for IC50 and the sigmodicity factor (gamma) were 3.7 (SD 1.2) pg ml-1 and 13.0 (SD 3.5), respectively. In most cases when there was a high urine flow rate at baseline, the model and the estimated PD parameters could be related to the pharmacological action of desmopressin and renal physiology. Thus, the indirect-response model used in this study offers a mechanistic approach of modeling the effect of desmopressin in overhydrated subjects.

Adult↗

A simplified method for separate measurements of lung and chest wall mechanics in ventilator-treated patients.

BACKGROUND: Airway pressure measurements above the endotracheal tube will be distorted because of endotracheal tube resistance. To separate lung and chest wall compliance, esophageal pressure is conventionally measured with an air-filled balloon catheter, which is difficult to insert in unconscious patients. We have developed a methodology with fluid-filled catheters for intratracheal and esophageal pressure measurements. METHODS: Twelve anesthetized patients were studied. Tidal volumes were measured by side-stream spirometry. Airway pressures were measured at the Y-piece and in the trachea with fluid-filled pressure lines. Esophageal pressure was measured via the narrow lumen in a fluid-filled Salem double-lumen stomach tube, which was slowly retracted from the stomach up through the esophagus until maximal respiratory pressure readings and minimal cardiac artifacts were obtained. Lung mechanics were measured at different tidal volumes (TV) and positive end-expiratory pressure (PEEP). RESULTS: There was a significant difference between airway pressures at the Y-piece and in the trachea. Total compliance significantly increased with increasing TV and decreased with increasing PEEP. Chest wall compliance increased significantly with increasing TV, while lung compliance did not change significantly. Two patients showed repeatedly marked increase in lung compliance at one specific ventilatory setting, an increase the proportion of which was not reflected by changes in total compliance. CONCLUSIONS: Y-piece pressures are not representative of intratracheal pressures, which can be measured by inserting a fluid-filled pressure line through the tube. Esophageal pressure is easily recorded with a fluid-filled Salem double-lumen catheter. Large changes in lung compliance may pass unnoticed when only total compliance is monitored. Monitoring of lung compliance may offer an improved basis for decisions about ventilator settings.

Adult↗

Atrial natriuretic peptide attenuates pacing-induced myocardial ischemia during general anesthesia in patients with coronary artery disease.

UNLABELLED: Atrial natriuretic peptide (ANP) exerts a dilatory effect on coronary arteries in humans. We investigated the effects of ANP on pacing-induced myocardial ischemia during enflurane anesthesia in patients with coronary artery disease (CAD). In 20 patients with CAD, myocardial ischemia was induced by atrial pacing before and after an i.v. infusion of ANP (50 mg x kg(-1) min(-1), n = 10) or placebo (n = 10). We studied the effects of ANP or placebo on pacing-induced changes in central hemodynamics, myocardial blood flow and regional myocardial indices of lactate uptake (RMLU), and oxygen consumption (RMVO2) and extraction (RMO2E). ST-segment depression was less pronounced during pacing with ANP compared with control pacing (-0.09 +/- 0.01 vs -0.24 +/- 0.02 mV; P < 0.001). RMLU decreased to -11.1 micromol/min during control pacing compared with -0.7 micromol/min during pacing with ANP (P < 0.01). ANP did not affect pacing-induced changes in RMVO2, RMO2E, or the rate pressure product. Placebo did not affect pacing-induced changes in ST-segment depression or RMLU. In conclusion, ANP attenuates ischemic ST-segment depression and lactate release during pacing-induced myocardial ischemia in patients with CAD. The antiischemic effect of ANP was not accompanied by any improvement in the regional myocardial oxygen supply/demand relationship. IMPLICATIONS: We evaluated the effects of i.v. atrial natriuretic peptide (50 ng x kg(-1) x min(-1)) on pacing-induced myocardial ischemia during general anesthesia in patients with coronary artery disease. In contrast to placebo, atrial natriuretic peptide attenuated ST-segment depression and myocardial lactate production and improved left ventricular function during pacing-induced ischemia.

Adult↗

Baroreceptor-mediated reduction of jejunal mucosal perfusion, evaluated with endoluminal laser Doppler flowmetry in conscious humans.

Reduction of central blood volume elicits a peripheral vasoconstrictor reflex in various tissues including skin, skeletal muscle and the hepatomesenteric region. The aim of the present study was to investigate whether this reaction includes a decreased perfusion of the jejunal mucosa in man. Laser Doppler flowmetry (LDF) was used to monitor jejunal mucosal and skin perfusion simultaneously in eleven healthy volunteers. LDF recordings were performed during quiescent (phase 1) periods of the migrating motor complex. Seven subjects demonstrated cycling changes of jejunal mucosal perfusion (vasomotion). The average minimum jejunal flux value was 72 +/- 6 perfusion units. The average intraindividual coefficient of variation was 18 +/- 2%. Lower body negative pressure (LBNP) was used to elicit controlled reductions of central blood volume. LBNP of 10 mm Hg induced a 12 +/- 4% (P < 0.05) decrease in jejunal perfusion and a 43 +/- 11 (P < 0.001) decrease in cutaneous perfusion. Corresponding responses to LBNP of 20 mm Hg were 17 +/- 5% (P < 0.01) and 37 +/- 10% (P < 0.01) reductions in jejunal mucosal and skin perfusion, respectively. Cardiac index was significantly reduced by the LBNP procedure, whereas heart rate remained unchanged and blood pressure changes were minor and inconsistent. These findings indicate that the reflex vasoconstriction induced by mild central hypovolemia includes a significant reduction of jejunal mucosal perfusion in supine resting humans. This reflex may provide one mechanism for the intestinal ischemia often occurring in critically ill patients.

Adult↗

Effect of nitric oxide gas on platelets during open heart operations.

BACKGROUND: The increased bleeding tendency observed after cardiopulmonary bypass is caused in part by thrombocytopenia and impaired platelet function induced by the procedure. Previous in vitro studies have shown that nitric oxide (NO) added to the oxygenator sweep gas reduces platelet activation during experimental perfusion. We evaluated the effect of 40 ppm of NO, added to the oxygenator sweep gas, on platelet consumption and activation in patients undergoing cardiopulmonary bypass. METHODS: Twenty patients scheduled to undergo cardiopulmonary bypass were randomized to either the control or the NO arm of the study. Their platelet count, plasma beta-thromboglobulin level, platelet membrane glycoprotein Ib and IIb/IIIa levels, adenosine diphosphate-induced platelet aggregation, plasma nitrate level, and plasma hemoglobin were assayed before, during, and after cardiopulmonary bypass. RESULTS: After operation, slightly higher platelet counts were observed in the NO-treated patients than in the control patients, which might indicate a lower degree of platelet adhesion to the artificial surfaces of the extracorporeal circuit. However, this difference did not reach statistical significance. In addition, a difference in platelet membrane expression of glycoprotein Ib was seen between the NO and control groups after operation; the platelets of the control patients had significantly higher glycoprotein Ib expression than those of the NO-treated patients. The results of platelet aggregometry indicated preserved platelet function in both the NO-treated and control patients. The blood methemoglobin levels also were low in both groups. CONCLUSIONS: Nitric oxide might reduce the platelet consumption encountered during cardiopulmonary bypass without having any adverse effect on platelet function, as reflected by the preserved aggregation response seen in our patients. However, the best route of NO administration and the optimum dose remain to be established.

Adenosine Diphosphate↗

Evaluation of a Pitot type spirometer in helium/oxygen mixtures.

OBJECTIVE: Mixtures of helium and oxygen are regaining a place in the treatment of obstruction of the upper and lower respiratory tract. The parenchymal changes during the course of IRDS or ARDS may also benefit from the reintroduction of helium/oxygen. In order to monitor and document the effect of low-density gas mixtures, we evaluated the Datex AS/3 Side Stream Spirometry module with D-lite (Datex-Engstrom Instrumentarium Corporation, Finland) against two golden standards. METHODS: Under conditions simulating controlled and spontaneous ventilation with gas mixtures of He (approx. 80, 50, and 20%)/O2 or N2(approx. 21 and 79%)/02, simultaneous measurements using Biotek Ventilator Tester (Bio-Tek Instr., Vermont, USA) or body plethysmograph (SensorMedics System, Anaheim, USA) were correlated with data from the spirometry module. Data were analyzed according to a statistical regression model resulting in a best-fit equation based on density, voltage, and volume measurements. RESULTS: As expected, the D-lite (a modified Pitot tube) showed density-dependent behaviour. Regression equations and percentage deviation of estimated versus measured values were calculated. CONCLUSION: Measurements with the D-lite using low-density gases are satisfactorily contained in best-fit equations with a standard deviation of less than 5% during all ventilatory modes and mixtures.

Airway Obstruction↗

Periventricular leukomalacia causes visual impairment in preterm children. A study on the aetiologies of visual impairment in a population-based group of preterm children born 1989-95 in the county of Värmland, Sweden.

PURPOSE: To determine the causes of visual impairment in a population-based group of visually impaired preterm children. METHODS: Ophthalmological examination and magnetic resonance imaging or computed tomography of the brain were performed in all visually impaired preterm children born 1989-95 in Värmland. RESULTS: Ten of 18 children had periventricular leukomalacia affecting the optic radiation, six had other lesions or malformations in the posterior visual pathways/cortex, but no child had visually impairing retinopathy of prematurity. CONCLUSION: We conclude that cerebral lesions or malformations are common causes of the visual functional deficit in visually impaired children born preterm. Brain damage should be suspected in a prematurely born child who presents with either of the signs: fixation difficulties, strabismus or nystagmus.

Adult↗

Bystander suppression of occupational hapten sensitization in rats made tolerant to ovalbumin.

Feeding a soluble antigen to an animal is known to cause a state of unresponsiveness against this antigen. If this antigen is given together with another antigen during the sensitization procedure, impairment of the response to the new antigen can also be seen, a phenomenon referred to as bystander suppression. The induction of tolerance against ovalbumin (OvA) and the effect of bystander suppression on the response to the hapten trimellitic anhydride (TMA), a cause of occupational asthma, were studied in Brown-Norway rats. Rats were fed either OvA-containing pellets or standard diet for 16 days before sensitization with the mixture of TMA and OvA. The animals were followed for 6 weeks after sensitization. Animals made tolerant to OvA showed a significantly suppressed delayed-type hypersensitivity (DTH) reaction against both OvA and TMA compared with the nontolerized control group at 5 weeks after sensitization, implying bystander suppression. By contrast, immunoglobulin (Ig)E and IgG antibody levels were suppressed only against OvA, whereas anti-TMA antibody levels were not affected. Airway eosinophilia after a single aerosol challenge at 6 weeks after sensitization using TMA conjugated to rat serum albumin, correlated with IgE anti-TMA levels in the group made tolerant to OvA and was not affected by OvA ingestion. In conclusion, suppressive factors released in ovalbumin-tolerant rats when they are challenged with ovalbumin, can suppress the response to trimellitic anhydride and this suppression is more pronounced for T-helper1-type responses.

Airway Resistance↗