Search

Background and Objectives: In fresh blood, tissue hypoxia increases microcirculatory acidosis, which enhances erythrocyte O(2) unloading and increases the amount of available O(2). Storage of erythrocytes increases the HbO(2) affinity and reduces O(2) unloading. We examined the development of the affinity change during a period of 5 weeks of storage by present blood bank standards, and investigated to what extent acidosis offsets the affinity change.Materials and Methods: Blood from volunteer donors was processed and stored as erythrocyte concentrates (EC). At 2-5 day intervals, EC were drawn from the bags and suspended in plasma and crystalloids to an Hb ≈ 10 g/dL. The suspensions were adjusted to give a pH of 7.40, 7.10, 6.80 or 6.30 and equilibrated with different gas mixtures to SO(2) 0, 25, 50, 75 and 100%. Measurements of the PO(2)/SO(2) pairs at each pH were used to calculate the position of the HbO(2) curve and its P(50) value.Results: A significant leftward shift in the HbO(2) curve was established after 1 week of storage; after 2.5 weeks only minor further changes were observed. Acidification right-shifted the HbO(2) curve, after 2.5 weeks of storage the curve at pH 7.10 was similar to that for fresh blood at pH 7.40. Calculations of extractable O(2) showed that the left-shifted HbO(2) curve of stored EC could be advantageous at a low arterial PO(2).Conclusions: The rightward shift of the HbO(2) curve due to acidosis is well maintained in stored erythrocytes, a moderate pH decrease offsets the storage-induced increased HbO(2) affinity. [ABSTRACT FROM AUTHOR]

Large-volume therapeutic phlebotomy is the mainstay of hemochromatosis treatment and offers an opportunity to investigate the hemodynamic changes during acute hypovolemia. An otherwise healthy 64-year-old male with hemochromatosis participated. On nine separate visits, 1000 mL therapeutic phlebotomy was performed. On one occasion, pre- and post-phlebotomy orthostatic challenge with 27° reverse Trendelenburg position was administered. Mean arterial pressure, heart rate, and stroke volume were measured continuously during the procedures. The patient's tolerance to the interventions was continuously evaluated. The procedures were well tolerated by the patient. Mean arterial pressure was maintained during hemorrhage and following phlebotomy in both supine and reverse Trendelenburg positions, primarily through an increase in heart rate and systemic vascular resistance. The present study found that 1000 mL therapeutic phlebotomy in a patient with hemochromatosis may be acceptably and safely used to model hemorrhage. The approach demonstrates high clinical applicability and ethically robustness in comparison with volunteer studies., (© 2024 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Acute poisoning caused by inhalation of carbon monoxide and other toxic substances is the primary cause of death in fires and may occur without signs of external injury. Life-threatening symptoms may arise immediately, as in cyanide poisoning, or over a longer period, as in carbon monoxide poisoning. Severe inhalation injury may also occur independently of systemic poisoning and should always be suspected in patients with soot on their face and in the respiratory tract, or hoarseness and wheezing.

Introduction: Removal of pulmonary secretions in mechanically ventilated patients usually requires suction with closed catheter systems or flexible bronchoscopes. Manual ventilation is occasionally performed during such procedures if clinicians suspect inadequate ventilation. Suctioning can also be performed with the ventilator entirely disconnected from the endotracheal tube (ETT). The aim of this study was to investigate if these two procedures generate negative airway pressures, which may contribute to atelectasis., Methods: The effects of device insertion and suctioning in ETTs were examined in a mechanical lung model with a pressure transducer inserted distal to ETTs of 9 mm, 8 mm and 7 mm internal diameter (ID). A 16 Fr bronchoscope and 12, 14 and 16 Fr suction catheters were used at two different vacuum levels during manual ventilation and with the ETTs disconnected., Results: During manual ventilation with ETTs of 9 mm, 8 mm and 7 mm ID, and bronchoscopic suctioning at moderate suction level, peak pressure (P PEAK ) dropped from 23, 22 and 24.5 cm H 2 O to 16, 16 and 15 cm H 2 O, respectively. Maximum suction reduced P PEAK to 20, 17 and 11 cm H 2 O, respectively, and the end-expiratory pressure fell from 5, 5.5 and 4.5 cm H 2 O to -2, -6 and -17 cm H 2 O. Suctioning through disconnected ETTs (open suction procedure) gave negative model airway pressures throughout the duration of the procedures., Conclusions: Manual ventilation and open suction procedures induce negative end-expiratory pressure during endotracheal suctioning, which may have clinical implications in patients who need high PEEP (positive end-expiratory pressure)., Competing Interests: Competing interests: None declared.

Background: The insertion of suction devices through endotracheal tubes (ETTs) increases airway resistance and the subsequent suctioning may reduce airway pressures and facilitate atelectasis. The aim of this study was to investigate how airway pressures and tidal volumes change when different combinations of suction equipment and ETT sizes are used, and to what extent unfavorable effects can be ameliorated by choice of ventilator settings., Methods: A mechanical ventilator was connected to a lung model by ETTs of 9 mm, 8 mm or 7 mm internal diameter (ID) with a pressure transducer inserted distal to the ETT. The effects of suction procedures with bronchoscope and closed catheter systems were investigated during pressure controlled ventilation (PCV) and volume controlled ventilation (VCV). In each mode, the effects of changes in inspiration:expiration (I:E) ratio, trigger sensitivity and suction pressure were examined., Results: The variables that contributed most to negative model airway pressures and loss of tidal volume during suctioning were (in descending order); 1) Small-size ETTs (7-8 mm ID) combined with large diameter suction devices (14-16 Fr); 2) inverse I:E ratio ventilation (in VCV); 3) negative ventilator trigger sensitivity; and 4) strong suction pressure. The pressure changes observed distal to the ETTs were not identical to those detected by the ventilator., Conclusions: Negative model airway pressure was induced by suctioning through small-size ETTs. The most extreme pressure and volume changes were ameliorated when conventional ventilator settings were used, such as PCV mode with short inspiration time and a trigger function sensitive to flow changes.

Background: Early intramedullary nailing (IMN) of long bone fractures in severely injured patients has been evaluated as beneficial, but has also been associated with increased inflammation, multi organ failure (MOF) and morbidity. This study was initiated to evaluate the impact of primary femoral IMN on coagulation-, fibrinolysis-, inflammatory- and cardiopulmonary responses in polytraumatized patients., Methods: Twelve adult polytraumatized patients with femoral shaft fractures were included. Serial blood samples were collected to evaluate coagulation-, fibrinolytic-, and cytokine activation in arterial blood. A flow-directed pulmonary artery (PA) catheter was inserted prior to IMN. Cardiopulmonary function parameters were recorded peri- and postoperatively. The clinical course of the patients and complications were monitored and recorded daily., Results: Mean Injury Severity Score (ISS) was 31 ± 2.6. No procedure-related effect of the primary IMN on coagulation- and fibrinolysis activation was evident. Tumor necrosis factor alpha (TNF-α) increased significantly from 6 hours post procedure to peak levels on the third postoperative day. Interleukin-6 (IL-6) increased from the first to the third postoperative day. Interleukin-10 (IL-10) peaked on the first postoperative day. A procedure-related transient hemodynamic response was observed on indexed pulmonary vascular resistance (PVRI) two hours post procedure. 11/12 patients developed systemic inflammatory response syndrome (SIRS), 7/12 pneumonia, 3/12 acute lung injury (ALI), 3/12 adult respiratory distress syndrome (ARDS), 3/12 sepsis, 0/12 wound infection., Conclusion: In the polytraumatized patients with femoral shaft fractures operated with primary IMN we observed a substantial response related to the initial trauma. We could not demonstrate any major additional IMN-related impact on the inflammatory responses or on the cardiopulmonary function parameters. These results have to be interpreted carefully due to the relatively few patients included., Trial Registration: ClinicalTrials.gov: NCT00981877.

Introduction: Operations in trauma patients represent a second insult and the extent of the surgical procedures influences the magnitude of the inflammatory response. Our hypothesis was that a reamer-irrigator-aspirator (RIA) system would cause a lesser inflammatory response than traditional reaming (TR)., Materials and Methods: Coagulation, fibrinolysis and cytokine responses were studied in Norwegian landrace pigs during and after intramedullary nailing (IMN) with two different reaming systems using ELISA and chromogenic peptide substrate assays. The TR (n=8) and the RIA (n=7) reaming systems were compared to a control group (n=7). The animals were followed for 72 h. Arterial, mixed venous and femoral vein blood were withdrawn simultaneously peroperatively and until 2 h after the nail was inserted for demonstration of local, pulmonary and systemic activation of the cascade systems. At 6 h, 24 h, 48 h and 72 h postoperatively arterial blood samples were withdrawn., Results: Significantly procedure-related increased levels were found for thrombin-antithrombin (TAT) and tissue plasminogen activator (t-PA) in the TR group and TAT in the RIA group. The local and the pulmonary activation of coagulation and fibrinolysis were more pronounced in the TR than in the RIA group, the difference reached significance for plasminogen activator inhibitor-1 (PAI-1) (arterial blood). The cytokine response, mainly represented by IL-6 increase, was more pronounced in the TR than the RIA group, and was significant for IL-6 in femoral vein blood. The arterial levels of IL-6 exceeded the mixed venous levels indicating an additional pulmonary activation of IL-6. Two animals in the TR group, who died of pulmonary embolism (PE) prior to planned study end point, had a more pronounced response compared to the rest of the TR group., Conclusion: A procedure-related coagulation and fibrinolytic response was demonstrated in both reaming groups, with more pronounced response in the TR than in the RIA group. Elevated levels of cytokines were demonstrated related to reaming and nailing, with significantly higher IL-6 levels in the TR than in the RIA group., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Introduction: Intramedullary orthopaedic procedures may increase the intramedullary pressure (IMP) and thereby cause intravasation of bone marrow contents. In recent studies by the authors the reamer-irrigator-aspirator (RIA) has been demonstrated to reduce IMP and coagulation-, fibrinolysis- and cytokine responses, but did not prove any significant difference in cardiopulmonary function parameters or numbers of emboli when compared to a traditional reaming (TR) system. The correlations between IMP increase, regardless type of reamer, and inflammatory- and coagulation responses, pulmonary embolization, and cardiopulmonary alterations have, however, not previously been analyzed in this material. Our hypothesis was that a lower IMP would result in reduced occurrence of pulmonary embolization, reduced inflammatory-and coagulation responses, as well as reduced cardiopulmonary alterations., Materials and Methods: Twenty-eight young Norwegian landrace pigs were exposed to femoral intramedullary reaming, with either the TR (n = 10) or the RIA (n = 10) system, or used as controls (n = 8). IMP was recorded during reaming and nailing. Serial blood samples for demonstration of coagulation-, fibrinolysis-, and cytokine activation were withdrawn peroperatively and until 72 hours post nail insertion. Circulatory and pulmonary effects were monitored peroperatively and until two hours postoperatively. The animals were sacrificed 72 hours post nail insertion and lung tissue biopsies were harvested and examined for lung emboli., Results and Conclusions: A strong correlation between increased IMP and increased coagulation-and cytokine responses was found. The number of emboli was not significantly correlated to IMP, but was strongly correlated to changes in the coagulation- and cytokine responses. No clinical relevant correlations were observed between increased IMP or numbers of lung emboli and changes in hemodynamic- or pulmonary function parameters. A correlation between coagulation activation and cytokine activation was observed. This study confirms the connection between increased IMP, increased coagulation activation and the magnitude of pulmonary emboli in a model evaluating the effects of intramedullary reaming of intact pig femora. In this model, the lowering of IMP during reaming, as obtained with RIA, reduced the magnitude of and the effects of bone marrow extravasation., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Background: Acute respiratory failure has an annual incidence of 20-75/100,000 and is the most common reason for admittance to an intensive care unit. A common cause is acute inflammatory changes in lung tissue. The article reviews clinical, etiological, pathophysiological and therapeutic aspects of acute respiratory failure, with an emphasis on failure secondary to proinflammatory processes., Material and Methods: This paper is not based on a comprehensive literature review, but on the clinical and scientific experience of the author, literature from a private archive and a limited Medline search., Results: Acute respiratory failure can be precipitated by agents and/or trauma that damage the lungs directly. Serious infections and tissue damage located in other parts of the body can also cause respiratory failure. In these cases, the blood transports activated blood cells and proinflammatory agents to the lungs where they induce secondary tissue inflammation. The resulting respiratory failure is often serious. Mortality is in the range 30-50 %., Interpretation: No specific treatment is available for secondary tissue inflammation; it usually resolves when the precipitating injuries or disease processes are healed. Positive pressure ventilation can prevent serious hypoxemia from causing additional damage to affected tissue. With modern treatment in an intensive care unit only 10-15 % of the deaths are caused by the respiratory failure per se, most deaths are caused by failure of several additional organs (multiorgan failure).

Increased nitrogen monoxide (NO) concentrations change leukocyte function under a multitude of experimental conditions. NO inhalation is an experimental treatment for lung failure and exposes leukocytes to increased NO concentrations during passage through the lungs. To investigate whether short-term NO inhalation induces lasting changes in the function of circulating human leukocytes, venous blood samples were drawn from eight healthy male volunteers before and at the end of a 35-min period of breathing 40 ppm NO in 30% O(2). The leukocytes in the samples were subsequently analyzed for NO-induced changes in expression of cell surface molecules, generation of reactive oxygen species (ROS), and cytokine production by flow cytometry and ELISA techniques. The results were (1) NO inhalation changed neither the baseline nor the Escherichia coli lipopolysaccharide (LPS)-induced expression of the cell adhesion molecules CD11a, CD11b, CD11c, and CD62L (l-selectin) on neutrophilic granulocytes (PMN) or monocytes (Mo). The expression of CD14 and HLA-DR was also unchanged. (2) The generation of ROS in response to activation with phorbol myristate acetate increased in PMN after NO inhalation; an increase in Mo did not reach significance. (3) Baseline and LPS-stimulated production of IL-1beta decreased after NO inhalation, while the LPS-stimulated production of TNF-alpha increased. No changes in IL-6 production were detected., (Copyright 2000 Academic Press.)

To gather further information about the effects on blood platelet activation of in vivo exposure to nitric oxide (NO), platelet reactivity was studied in blood from healthy, non-smoking male volunteers before and after 30 min inhalation of 40 ppm NO. Whole blood was stimulated in vitro with adenosine diphosphate or thrombin receptor activation peptide (TRAP-6). In an ex vivo perfusion model, non-anticoagulated blood was exposed to immobilised collagen at arterial blood flow conditions (2600 s(-1)). Blood samples from both the in vitro and ex vivo experiments were stained with fluorochrome-labelled Annexin-V and antibodies against CD42a, CD45, CD49b, CD61, CD62P and fibrinogen, and analysed with a three-colour flow cytometry technique. NO inhalation reduced the platelet activation response to adenosine diphosphate (ADP) stimulation by decreasing platelet-platelet aggregation, alpha-granule release and platelet-leukocyte conjugate formation. TRAP-stimulated platelet activation, collagen-induced platelet activation and thrombus growth was unaffected by NO inhalation. We therefore suggest an ADP receptor inhibitor mode of action of inhaled NO, selective on the newly suggested G protein- and phospholipase C-coupled P2Y1 receptor. Our results demonstrate that blood platelet activation in healthy subjects is modulated by inhalation of NO in therapeutically relevant doses, although the clinical impact of our findings remains unclear.

Objectives: To determine the oxyhemoglobin dissociation curve in blood with pH of approximately 6.3 due to metabolic and superimposed respiratory acidosis, and to evaluate the oxygen delivery capacity of the blood under these circumstances., Design: In vitro study., Setting: A blood gas laboratory in a university institute for respiratory physiology., Subjects: Heparinized normal human blood., Interventions: The oxyhemoglobin dissociation curve was determined by measuring PO2, pH, PCO2, and hemoglobin oxygen saturation at 37 degrees C in mixtures of blood from two reservoirs, both prepared by titration with lactic acid to a pH of 6.3 during tonometry with gases containing 4.2% CO2 and high and low oxygen percentages, respectively. For determination of the effect of additional increases in PCO2, the reservoir blood thus produced was prepared by further tonometry with gases containing 12.8% CO2 and the same oxygen percentages., Measurements and Main Results: With the same degree of lactic acidosis (blood lactate concentration of 52 mmol/L), the position of the oxyhemoglobin dissociation curve was the same for blood with PCO2 of 30 torr (4 kPa) and pH of 6.295 and for blood with PCO2 of 90 torr (12 kPa) and pH of 6.165. During tonometry with a gas with PCO2 of 30 torr (4 kPa) and PO2 of 20 torr (2.7 kPa) and addition of increasing amounts of lactic acid, leading to a stepwise change in pH from 6.7 to 6.0, hemoglobin oxygen saturation decreased with decreasing pH from 6.7 to 6.4, but remained the same at a pH of between 6.4 and 6.0. The measured rightward shift of the oxyhemoglobin dissociation curve at such a low pH was clearly less pronounced than that calculated using commonly applied equations, in particular, at the lowest pH. The beneficial effects of the rightward shift of the oxyhemoglobin dissociation curve on the estimates of extractable oxygen at a given venous PO2 decrease with decreasing pH, and disappear rapidly when the Pao2 is reduced below normal., Conclusions: The acidemia-induced rightward shift of the oxyhemoglobin dissociation curve does not increase further at a pH < 6.4, and is, at such extreme acidemia, less pronounced than calculated by the commonly used equations. To obtain optimal tissue oxygenation in patients with severe circulatory failure and extreme metabolic acidosis, Pao2 should be > 250 torr (> 33.3 kPa).

The general symptoms of upper airway obstruction are described, as well as the specific symptoms expected to be found in various conditions that cause such obstruction. An algorithm, intended primarily for general practitioners and other physicians who seldom confront such problems, describes the procedures for establishing an unobstructed airway in different situations. It also outlines the interventions necessary to ensure adequate oxygenation and ventilation when such procedures fail. Special emphasis is placed on the use of emergency tracheotomy, or oxygenation by means of cricothyreoid membrane puncture, as an alternative to emergency intubation by unskilled physicians.

Unlabelled: Generation of reactive oxygen intermediates by activated polymorphonuclear neutrophil granulocytes plays an important role in development of microcirculatory injury. The effect of the beta 2-adrenergic receptor agonists (beta 2-agonists) isoprenaline and terbutaline on the chemiluminescence or oxygen consumption of human granulocytes in response to activation with n-formyl-methionyl-leucyl-phenylalanine (FMLP) and phorbol myristate acetate (PMA) was examined. The beta 2-agonist effect on activated cell aggregation and volume change was examined as well. As E. Coli lipopolysaccharide and FMLP may prime granulocytes for enhanced generation of reactive oxygen intermediates in response to other activators, the effect of beta 2-agonists on the priming effect of these agents was also investigated., Results: 1) Optimal concentrations of beta 2-agonists decrease the human granulocyte generation of reactive oxygen intermediates in response to activation with FMLP by 40-60%, without affecting the response to PMA. 2) beta 2-Agonists modify the priming effect of FMLP on activation with PMA, but do not interfere with the priming effect of E. Coli lipopolysaccharide on activation with FMLP. 3) Isoprenaline have different effects on generation of reactive oxygen intermediates and cell aggregation in FMLP-activated granulocytes. 4) High concentrations of isoprenaline and terbutaline have contrasting non-specific effects on the chemiluminescence, but not on the oxygen consumption, of activated granulocytes.

Polymorphonuclear neutrophil granulocytes (PMN) may contribute to the lung injury induced by nonpulmonary infections with gram-negative bacteria. The direct effect of E. coli lipopolysaccharide (LPS) on isolated human PMN or mixed leukocytes (ML), as well as the priming effect of preincubating cells with LPS, was examined in assays measuring the maximal rate of oxygen consumption (OC), cell chemiluminescence (CHML), and aggregation (AGG). LPS, 1-10 micrograms/ml, caused no acute response in PMN or ML suspended in Fisher's-HEPES medium with BSA (FHA), but increased both CHML and AGG of cells suspended in autologous plasma. Preincubation in FHA with LPS, 1 microgram/ml, for more than 15 min increased the OC of PMN activated with zymosan-activated plasma (ZAP) or n-formyl-methionyl-leu-cyl-phenylalanine (FMLP) by more than 100%. A similar increase in the CHML of such cells was seen after FMLP, but not after ZAP. ZAP, however, primed the CHML response of the cells to subsequent activation with FMLP more than did preincubation with LPS. Previous exposure to both agents had an additive effect. Preincubation of PMN with LPS decreased the time interval from addition of phorbol myristate acetate (PMA) to peak OC response, but less so than previous activation with FMLP. Neither agent affected the maximal rate of OC after addition of PMA. LPS also increased the PMN aggregation induced by ZAP and FMLP, but not by PMA. Cells preincubated with LPS, 0.01 microgram/ml, increased their CHML in response to FMLP if suspended in Krebs-Ringer balanced salt solution, but not if suspended in FHA. Such preincubation had no effect on OC of similarly activated cells in any of the media.

Interstitial fluid pressure was measured in nine isolated perfused rabbit lungs with the servonull micropipette method. Bevelled glass micropipettes, with tip diameter 2-6 micrometers (o.d.) were inserted 2-6 mm into the left lung. At alveolar pressures of 3 to 5 cm H2O we found mean interstitial fluid pressures of 1.0 (SD 1.0) and 1.6 (SD 1.0) cm H2O relative to pleural pressure in the upper (n = 19) and lower (n = 21) lobes respectively. The vertical distance between the measuring sites in the upper and lower lobes was about 3 cm. Net filtration caused by elevated left atrial pressure caused practically no change in interstitial fluid pressure. Increased alveolar pressure either increased or decreased interstitial fluid pressure. The measured pressures probably represent interstitial fluid pressure in alveolar junctions or in the interstitium around small pulmonary arteries or veins. We conclude that interstitial fluid pressure in these sites is between alveolar and pleural pressure, and that it is only moderately affected by changes in alveolar pressure. The interstitial compliance appears to be high and there seem to be little or no vertical gradients in interstitial fluid pressure within the lung.

The ability of two polymorphonuclear granulocyte (PMN) activators, Zymosan activated plasma (ZAP) and Phorbol myristate acetate (PMA), to induce an adult respiratory distress syndrome (ARDS) type lung injury was compared in awake and anaesthetized rabbits. The preparatory procedure itself decreased the concentrations of circulating PMN and lymphocytes in anaesthetized animals. ZAP acutely lowered the number of circulating leukocytes due to a fall in PMN only, this was followed by a rebound. Both effects were more marked in awake than in anaesthetized animals. PMA caused a virtual disappearance of both PMN and lymphocytes from the blood. There was no rebound, and no difference between anaesthetized and awake animals. The activators caused equal increases in pulmonary arterial pressure (about 0.67 kPa) initially. This was followed by a return to baseline in ZAP animals, but a further increase in those given PMA. Increased airway pressure (0.4 kPa) was seen only in the PMA group; PaO2 decreased only in awake rabbits given PMA. Both activators, as well as the preparatory procedure itself, caused PMN accumulations in the alveolar septa, septal thickening, and modest perivascular edema with intact tissue architecture. PMA caused the most marked changes. Wet/dry lung weight ratios were only moderately increased. In conclusion, ZAP and PMA had different effects on circulating leukocytes, but gave nearly the same degree of PMN accumulation in the lungs. The modest edema indicated some increased microvascular leakage, but a fully developed ARDS-type lung injury did not occur.