11 results on '"Osvaldo BIANCOLILLI"'
Search Results
2. Lung Biomolecular Profile and Function of Grafts from Donors after Cardiocirculatory Death with Prolonged Donor Warm Ischemia Time
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Grasselli, Francesca Gori, Jacopo Fumagalli, Caterina Lonati, Andrea Carlin, Patrizia Leonardi, Osvaldo Biancolilli, Antonello Rossetti, Ilaria Righi, Davide Tosi, Alessandro Palleschi, Lorenzo Rosso, Letizia Corinna Morlacchi, Francesco Blasi, Luigi Vivona, Gaetano Florio, Vittorio Scaravilli, Franco Valenza, Alberto Zanella, and Giacomo
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ex vivo lung perfusion ,glycocalyx ,coagulation ,inflammasome ,lung transplantation - Abstract
The acceptable duration of donor warm ischemia time (DWIT) after cardiocirculatory death (DCD) is still debated. We analyzed the biomolecular profile and function during ex vivo lung perfusion (EVLP) of DCD lungs and their correlation with lung transplantation (LuTx) outcomes. Donor data, procurement times, recipient outcomes, and graft function up to 1 year after LuTx were collected. During EVLP, the parameters of graft function and metabolism, perfusate samples to quantify inflammation, glycocalyx breakdown products, coagulation, and endothelial activation markers were obtained. Data were compared to a cohort of extended-criteria donors after brain death (EC-DBD). Eight DBD and seven DCD grafts transplanted after EVLP were analyzed. DCD’s DWIT was 201 [188;247] minutes. Donors differed only regarding the duration of mechanical ventilation that was longer in the EC-DBD group. No difference was observed in lung graft function during EVLP. At reperfusion, “wash-out” of inflammatory cells and microthrombi was predominant in DCD grafts. Perfusate biomolecular profile demonstrated marked endothelial activation, characterized by the presence of inflammatory mediators and glycocalyx breakdown products both in DCD and EC-DBD grafts. Early graft function after LuTx was similar between DCD and EC-DBD. DCD lungs exposed to prolonged DWIT represent a potential resource for donation if properly preserved and evaluated.
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- 2022
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3. Inhaled CO2 vs. Hypercapnia Obtained by Low Tidal Volume or Instrumental Dead Space in Unilateral Pulmonary Artery Ligation: Any Difference for Lung Protection?
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Elena Spinelli, Antonio Pesenti, Gianluca Lopez, Anna Damia, Francesco Damarco, Erica Garbelli, Gaia Dal Santo, Alessio Caccioppola, Giorgio Giudici, Virginia Figgiaconi, Osvaldo Biancolilli, Michele Battistin, Caterina Lonati, Valentina Vaira, Lorenzo Rosso, Stefano Ferrero, Stefano Gatti, and Tommaso Mauri
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General Medicine - Abstract
BackgroundUnilateral ligation of the pulmonary artery (UPAL) induces bilateral lung injury in pigs undergoing controlled mechanical ventilation. Possible mechanisms include redistribution of ventilation toward the non-ligated lung and hypoperfusion of the ligated lung. The addition of 5% CO2 to the inspiratory gas (FiCO2) prevents the injury, but it is not clear whether lung protection is a direct effect of CO2 inhalation or it is mediated by plasmatic hypercapnia. This study aims to compare the effects and mechanisms of FiCO2vs. hypercapnia induced by low tidal volume ventilation or instrumental dead space.MethodsHealthy pigs underwent left UPAL and were allocated for 48 h to the following: Volume-controlled ventilation (VCV) with VT 10 ml/kg (injury, n = 6); VCV plus 5% FiCO2 (FiCO2, n = 7); VCV with VT 6 ml/kg (low VT, n = 6); VCV plus additional circuit dead space (instrumental VD, n = 6). Histological score, regional compliance, wet-to-dry ratio, and inflammatory infiltrate were assessed to evaluate lung injury at the end of the study. To investigate the mechanisms of protection, we quantified the redistribution of ventilation to the non-ligated lung, as the ratio between the percentage of tidal volume to the right and to the left lung (VTRIGHT/LEFT), and the hypoperfusion of the ligated lung as the percentage of blood flow reaching the left lung (PerfusionLEFT).ResultsIn the left ligated lung, injury was prevented only in the FiCO2 group, as indicated by lower histological score, higher regional compliance, lower wet-to-dry ratio and lower density of inflammatory cells compared to other groups. For the right lung, the histological score was lower both in the FiCO2 and in the low VT groups, but the other measures of injury showed lower intensity only in the FiCO2 group. VTRIGHT/LEFT was lower and PerfusionLEFT was higher in the FiCO2 group compared to other groups.ConclusionIn a model of UPAL, inhaled CO2 but not hypercapnia grants bilateral lung protection. Mechanisms of protection include reduced overdistension of the non-ligated and increased perfusion of the ligated lung.
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- 2022
4. Addition of 5% CO2 to Inspiratory Gas Prevents Lung Injury in an Experimental Model of Pulmonary Artery Ligation
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Gianluca Lopez, Eleonora Scotti, Stefano Ferrero, Valentina Vaira, Alessandra Mazzucco, Elena Spinelli, Tommaso Mauri, Ines Marongiu, Michele Battistin, Osvaldo Biancolilli, Thomas Langer, Francesca Roma, Giulia Colussi, Caterina Lonati, Stefano Gatti, Antonio Pesenti, Leonardo Manesso, Lorenzo Rosso, Yu Mei Wang, Alberto Zanella, Marongiu, I, Spinelli, E, Scotti, E, Mazzucco, A, Wang, Y, Manesso, L, Colussi, G, Biancolilli, O, Battistin, M, Langer, T, Roma, F, Lopez, G, Lonati, C, Vaira, V, Rosso, L, Ferrero, S, Gatti, S, Zanella, A, Pesenti, A, and Mauri, T
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Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,Critical Care ,VILI ,Lung injury ,Critical Care and Intensive Care Medicine ,Ischemia ,medicine.artery ,Internal medicine ,medicine ,Humans ,Lung ,inhalation ,CO2 inhalation ,Experimental model ,business.industry ,Original Articles ,Carbon Dioxide ,pulmonary perfusion ,CO ,Reperfusion Injury ,Pulmonary artery ,Cardiology ,Ligation ,business ,therapeutic hypercapnia - Abstract
Rationale: Unilateral ligation of the pulmonary artery may induce lung injury through multiple mechanisms, which might be dampened by inhaled CO2. Objectives: This study aims to characterize bilateral lung injury owing to unilateral ligation of the pulmonary artery in healthy swine undergoing controlled mechanical ventilation and its prevention by 5% CO2 inhalation and to investigate relevant pathophysiological mechanisms. Methods: Sixteen healthy pigs were allocated to surgical ligation of the left pulmonary artery (ligation group), seven to surgical ligation of the left pulmonary artery and inhalation of 5% CO2 (ligation + FiCO2 5%), and six to no intervention (no ligation). Then, all animals received mechanical ventilation with Vt 10 ml/kg, positive end-expiratory pressure 5 cm H2O, respiratory rate 25 breaths/min, and FiO2 50% (±FiCO2 5%) for 48 hours or until development of severe lung injury. Measurements and Main Results: Histological, physiological, and quantitative computed tomography scan data were compared between groups to characterize lung injury. Electrical impedance tomography and immunohistochemistry analysis were performed in a subset of animals to explore mechanisms of injury. Animals from the ligation group developed bilateral lung injury as assessed by significantly higher histological score, larger increase in lung weight, poorer oxygenation, and worse respiratory mechanics compared with the ligation + FiCO2 5% group. In the ligation group, the right lung received a larger fraction of Vt and inflammation was more represented, whereas CO2 dampened both processes. Conclusions: Mechanical ventilation induces bilateral lung injury within 48 hours in healthy pigs undergoing left pulmonary artery ligation. Inhalation of 5% CO2 prevents injury, likely through decreased stress to the right lung and antiinflammatory effects.
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- 2021
5. Inhaled CO
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Elena, Spinelli, Antonio, Pesenti, Gianluca, Lopez, Anna, Damia, Francesco, Damarco, Erica, Garbelli, Gaia, Dal Santo, Alessio, Caccioppola, Giorgio, Giudici, Virginia, Figgiaconi, Osvaldo, Biancolilli, Michele, Battistin, Caterina, Lonati, Valentina, Vaira, Lorenzo, Rosso, Stefano, Ferrero, Stefano, Gatti, and Tommaso, Mauri
- Abstract
Unilateral ligation of the pulmonary artery (UPAL) induces bilateral lung injury in pigs undergoing controlled mechanical ventilation. Possible mechanisms include redistribution of ventilation toward the non-ligated lung and hypoperfusion of the ligated lung. The addition of 5% COHealthy pigs underwent left UPAL and were allocated for 48 h to the following: Volume-controlled ventilation (VCV) with VIn the left ligated lung, injury was prevented only in the FiCOIn a model of UPAL, inhaled CO
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- 2022
6. A Minimally Invasive and Highly Effective Extracorporeal CO2 Removal Device Combined With a Continuous Renal Replacement Therapy
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Alberto Zanella, Antonio Pesenti, Mattia Busana, Stefano De Falco, Luca Di Girolamo, Eleonora Scotti, Ilaria Protti, Sebastiano Maria Colombo, Vittorio Scaravilli, Osvaldo Biancolilli, Andrea Carlin, Francesca Gori, Michele Battistin, Daniele Dondossola, Federica Pirrone, Domenico Salerno, Stefano Gatti, Giacomo Grasselli, Zanella, A, Pesenti, A, Busana, M, De Falco, S, Di Girolamo, L, Scotti, E, Protti, I, Colombo, S, Scaravilli, V, Biancolilli, O, Carlin, A, Gori, F, Battistin, M, Dondossola, D, Pirrone, F, Salerno, D, Gatti, S, and Grasselli, G
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Continuous Renal Replacement Therapy ,Swine ,gas exchange ,mechanical ventilation ,Carbon Dioxide ,Critical Care and Intensive Care Medicine ,Respiration, Artificial ,extracorporeal support ,ion-exchange resin ,extracorporeal carbon dioxide removal ,Oxygen ,acidification ,Dialysis Solutions ,Animals ,Humans ,Female - Abstract
OBJECTIVES: Extracorporeal carbon dioxide removal is used to treat patients suffering from acute respiratory failure. However, the procedure is hampered by the high blood flow required to achieve a significant CO2clearance. We aimed to develop an ultralow blood flow device to effectively remove CO2combined with continuous renal replacement therapy (CRRT). DESIGN: Preclinical, proof-of-concept study. SETTING: An extracorporeal circuit where 200 mL/min of blood flowed through a hemofilter connected to a closed-loop dialysate circuit. An ion-exchange resin acidified the dialysate upstream, a membrane lung to increase Pco2and promote CO2removal. PATIENTS: Six, 38.7 ± 2.0-kg female pigs. INTERVENTIONS: Different levels of acidification were tested (from 0 to 5 mEq/min). Two l/hr of postdilution CRRT were performed continuously. The respiratory rate was modified at each step to maintain arterial Pco2at 50 mm Hg. MEASUREMENTS AND MAIN RESULTS: Increasing acidification enhanced CO2removal efficiency of the membrane lung from 30 ± 5 (0 mEq/min) up to 145 ± 8 mL/min (5 mEq/min), with a 483% increase, representing the 73% ± 7% of the total body CO2production. Minute ventilation decreased accordingly from 6.5 ± 0.7 to 1.7 ± 0.5 L/min. No major side effects occurred, except for transient tachycardia episodes. As expected from the alveolar gas equation, the natural lung Pao2dropped at increasing acidification steps, given the high dissociation between the oxygenation and CO2removal capability of the device, thus Pao2decreased. CONCLUSIONS: This new extracorporeal ion-exchange resin-based multiple-organ support device proved extremely high efficiency in CO2removal and continuous renal support in a preclinical setting. Further studies are required before clinical implementation.
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- 2022
7. Atelectasis, Shunt, and Worsening Oxygenation Following Reduction of Respiratory Rate in Healthy Pigs Undergoing ECMO: An Experimental Lung Imaging Study
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Elena Spinelli, Giulia Colussi, Gaia Dal Santo, Eleonora Scotti, Ines Marongiu, Erica Garbelli, Alessandra Mazzucco, Daniele Dondossola, Raquel Maia, Michele Battistin, Osvaldo Biancolilli, Lorenzo Rosso, Stefano Gatti, and Tommaso Mauri
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medicine.medical_specialty ,Respiratory rate ,Physiology ,medicine.medical_treatment ,respiratory rate ,Atelectasis ,Respiratory physiology ,lcsh:Physiology ,Physiology (medical) ,Internal medicine ,atelectasis ,medicine ,Extracorporeal membrane oxygenation ,Original Research ,Lung ,lcsh:QP1-981 ,business.industry ,Oxygenation ,respiratory system ,extracorporeal membrane oxygenation ,medicine.disease ,shunt ,Hypoventilation ,medicine.anatomical_structure ,expiratory time ,Breathing ,Cardiology ,medicine.symptom ,business - Abstract
Rationale: Reducing the respiratory rate during extracorporeal membrane oxygenation (ECMO) decreases the mechanical power, but it might induce alveolar de-recruitment. Dissecting de-recruitment due to lung edema vs. the fraction due to hypoventilation may be challenging in injured lungs.Objectives: We characterized changes in lung physiology (primary endpoint: development of atelectasis) associated with progressive reduction of the respiratory rate in healthy animals on ECMO.Methods: Six female pigs underwent general anesthesia and volume control ventilation (Baseline: PEEP 5 cmH2O, Vt 10 ml/kg, I:E = 1:2, FiO2 0.5, rate 24 bpm). Veno-venous ECMO was started and respiratory rate was progressively reduced to 18, 12, and 6 breaths per minute (6-h steps), while all other settings remained unchanged. ECMO blood flow was kept constant while gas flow was increased to maintain stable PaCO2.Measurements and Main Results: At Baseline (without ECMO) and toward the end of each step, data from quantitative CT scan, electrical impedance tomography, and gas exchange were collected. Increasing ECMO gas flow while lowering the respiratory rate was associated with an increase in the fraction of non-aerated tissue (i.e., atelectasis) and with a decrease of tidal ventilation reaching the gravitationally dependent lung regions (p = 0.009 and p = 0.018). Intrapulmonary shunt increased (p < 0.001) and arterial PaO2 decreased (p < 0.001) at lower rates. The fraction of non-aerated lung was correlated with longer expiratory time spent at zero flow (r = 0.555, p = 0.011).Conclusions: Progressive decrease of respiratory rate coupled with increasing CO2 removal in mechanically ventilated healthy pigs is associated with development of lung atelectasis, higher shunt, and poorer oxygenation.
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- 2021
8. Human Red Blood Cells as Oxygen Carriers to Improve Ex-Situ Liver Perfusion in a Rat Model
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Stefania Villa, Daniele Dondossola, Alberto Zanella, Osvaldo Biancolilli, Stefano Gatti, Alessandro Santini, Michele Battistin, Caterina Lonati, Marco Maggioni, Luigi Vivona, Riccardo Merighi, and Alessandro Galli
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Liver perfusion ,Potassium ,Rat model ,lcsh:Medicine ,chemistry.chemical_element ,Cold storage ,normothermic machine perfusion ,rat ,human red blood cells ,oxygen consumption ,oxygen delivery ,030230 surgery ,Hematocrit ,Oxygen ,Article ,Andrology ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Machine perfusion ,medicine.diagnostic_test ,business.industry ,lcsh:R ,General Medicine ,chemistry ,Oxygen delivery ,030211 gastroenterology & hepatology ,business - Abstract
Ex-situ machine perfusion (MP) has been increasingly used to enhance liver quality in different settings. Small animal models can help to implement this procedure. As most normothermic MP (NMP) models employ sub-physiological levels of oxygen delivery (DO2), the aim of this study was to investigate the effectiveness and safety of different DO2, using human red blood cells (RBCs) as oxygen carriers on metabolic recovery in a rat model of NMP. Four experimental groups (n = 5 each) consisted of (1) native (untreated/control), (2) liver static cold storage (SCS) 30 min without NMP, (3) SCS followed by 120 min of NMP with Dulbecco-Modified-Eagle-Medium as perfusate (DMEM), and (4) similar to group 3, but perfusion fluid was added with human RBCs (hematocrit 15%) (BLOOD). Compared to DMEM, the BLOOD group showed increased liver DO2 (p = 0.008) and oxygen consumption ( V O ˙ 2) (p < 0.001); lactate clearance (p < 0.001), potassium (p < 0.001), and glucose (p = 0.029) uptake were enhanced. ATP levels were likewise higher in BLOOD relative to DMEM (p = 0.031). V O ˙ 2 and DO2 were highly correlated (p < 0.001). Consistently, the main metabolic parameters were directly correlated with DO2 and V O ˙ 2. No human RBC related damage was detected. In conclusion, an optimized DO2 significantly reduces hypoxic damage-related effects occurring during NMP. Human RBCs can be safely used as oxygen carriers.
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- 2019
9. Procurement and ex-situ perfusion of isolated slaughterhouse-derived livers as a model of donors after circulatory death
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Osvaldo Biancolilli, Mattia Busana, Francesco Carù, Stefano de Falco, Alberto Zanella, Stefano Gatti, Caterina Lonati, Luca Di Girolamo, Alessia Kersik, Daniele Dondossola, and Marco Maggioni
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Pharmacology ,Pathology ,medicine.medical_specialty ,Machine perfusion ,business.industry ,Respiratory chain ,Cold storage ,Histology ,General Medicine ,030230 surgery ,03 medical and health sciences ,Medical Laboratory Technology ,chemistry.chemical_compound ,0302 clinical medicine ,medicine.anatomical_structure ,chemistry ,Hepatocyte ,medicine ,030211 gastroenterology & hepatology ,Animal studies ,business ,Indocyanine green ,Perfusion - Abstract
Ex-situ machine perfusion (MP) techniques are increasingly used in clinical settings, especially on grafts derived from donors after cardiac death (DCD). However, comprehension of biological effects elicited during MP are largely unknown and a substantial number of animal studies are presently focused on this topic. The aim of the present study was to describe a model of DCD based on ex-situ perfusion of liver grafts derived from animals dedicated to food production. Procurement took place within a slaughterhouse facility. A clinically fashioned closed circuit normothermic MP (NMP) was built up. Autologous blood-enriched perfusion fluid was adopted. Perfusate and tissue samples were collected to asses NMP functionality. Grafts were classified as transplantable (LT-G) or not (n-LT) according to clinical criteria, while histopathological analysis was used to confirm graft viability. After cold storage, the liver grafts were connected to the NMP. During the rewarming phase, temperature and flows were progressively increased to reach target values. At the end of NMP, 4 grafts were classified as LT-G and 3 nLT-G. Histology confirmed absence of major damage in LT-G, while diffuse necrosis appeared in nLT-G. Interestingly, in nLT-G an early impairment of hepatocyte respiratory chain, leading to cell necrosis and graft non-viability, was documented for the first time. These parameters, together with indocyanine-green dye and citrate clearance could contribute to graft evaluation in clinical settings. In conclusion, this model provides a promising and reproducible method to replace dedicated experimental animals in DCD and MP research, in line with the 3Rs principles.
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- 2019
10. An Artificial Cough Maneuver to Remove Secretions From Below the Endotracheal Tube Cuff
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Osvaldo Biancolilli, Emanuele Rezoagli, Paolo Cadringer, Eleonora Carlesso, Martina Pastore, Antonio Pesenti, Vittorio Scaravilli, Gaetano Florio, Giuseppe Ristagno, Alberto Zanella, Zanella, A, Florio, G, Rezoagli, E, Pastore, M, Cadringer, P, Biancolilli, O, Carlesso, E, Scaravilli, V, Ristagno, G, and Pesenti, A
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Pulmonary and Respiratory Medicine ,medicine.medical_treatment ,Hemodynamics ,Suction ,Critical Care and Intensive Care Medicine ,03 medical and health sciences ,Mechanical ventilation ,0302 clinical medicine ,In vitro ,Materials Testing ,medicine ,Intubation, Intratracheal ,Pulmonary Elimination ,Ventilator-associated pneumonia ,Intubation ,Humans ,MED/41 - ANESTESIOLOGIA ,Respiratory system ,Saline ,Ventilators, Mechanical ,business.industry ,General Medicine ,Equipment Design ,medicine.disease ,Respiration, Artificial ,030228 respiratory system ,Cough ,Exhalation ,Anesthesia ,Cuff ,Endotracheal tube cuff ,business ,Human - Abstract
BACKGROUND: Endotracheal suctioning is mandatory to prevent complications caused by the retention of tracheal secretions. Endotracheal suctioning is often performed late, when patients show signs of respiratory and hemodynamic alterations. We conceived a prototype device that, when synchronized with the ventilator, automatically removes secretions collected below the endotracheal tube (ETT) cuff, thus avoiding endotracheal suctioning. The aim of our investigation was to assess the performance of this novel prototype in vitro. METHODS: Three studies were performed to examine the characteristics of the prototype. We tested device9s ability to generate an effective artificial cough flow (artificial cough maneuver) > 1 L/s by rapidly deflating the ETT cuff within the time of a sustained inflation (at 30 and at 40 cm H2O) (cough flow study). We also tested the prototype9s ability to remove the fluid positioned below the ETT cuff using saline dye (fluid removal study), and to prevent the aspiration of saline dye from above the ETT cuff during the deflation phase of the ETT cuff (aspiration study). The trachea model was positioned at 45° in the aspiration study, and horizontally in the other two studies. RESULTS: In the cough flow study, the prototype provided an effective artificial cough maneuver, with a mean ± SD of 1.78 ± 0.19 L/s (range, 1.42–2.14 L/s). The tracheal pressure after ETT cuff deflation never decreased below the PEEP level. In the fluid removal study, the prototype cleared the fluid from below the ETT cuff and the experimental trachea. No fluid was aspirated from the area above the ETT cuff toward the lower airways. CONCLUSIONS: We conceived an system capable of automatically expelling fluid from below the ETT cuff outside an experimental trachea by generating an artificial cough maneuver. This system may decrease the use of endotracheal suctioning and its complications. Future in vivo studies are needed to confirm this first in vitro evaluation.
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- 2019
11. Effects of sodium citrate, citric acid and lactic acid on human blood coagulation
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Eleonora Scotti, Caterina Lonati, Osvaldo Biancolilli, Patrizia Leonardi, Alberto Zanella, Andrea Carlin, Luca Di Girolamo, Antonio Pesenti, Mauro Panigada, Mattia Busana, and Vittorio Scaravilli
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Male ,030204 cardiovascular system & hematology ,Sodium Citrate ,Extracorporeal ,Citric Acid ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Sodium citrate ,Medicine ,Coagulation (water treatment) ,Humans ,Radiology, Nuclear Medicine and imaging ,Lactic Acid ,Blood Coagulation ,Advanced and Specialized Nursing ,Chromatography ,Human blood ,business.industry ,Extracorporeal circulation ,Anticoagulants ,030208 emergency & critical care medicine ,General Medicine ,Healthy Volunteers ,Lactic acid ,chemistry ,Anticoagulant Agent ,Female ,Cardiology and Cardiovascular Medicine ,Citric acid ,business ,Safety Research - Abstract
Introduction:Citric acid infusion in extracorporeal blood may allow concurrent regional anticoagulation and enhancement of extracorporeal CO2removal. Effects of citric acid on human blood thromboelastography and aggregometry have never been tested before.Methods:In this in vitro study, citric acid, sodium citrate and lactic acid were added to venous blood from seven healthy donors, obtaining concentrations of 9 mEq/L, 12 mEq/L and 15 mEq/L. We measured gas analyses, ionized calcium (iCa++) concentration, activated clotting time (ACT), thromboelastography and multiplate aggregometry. Repeated measure analysis of variance was used to compare the acidifying and anticoagulant properties of the three compounds.Results:Sodium citrate did not affect the blood gas analysis. Increasing doses of citric and lactic acid progressively reduced pH and HCO3−and increased pCO2(p++, from 0.39 (0.36-0.39) and 0.35 (0.33-0.36) mmol/L, respectively, at 9 mEq/L to 0.20 (0.20-0.21) and 0.21 (0.20-0.23) mmol/L at 15 mEq/L (p++(p=0.07). Sodium citrate and citric acid similarly incremented the ACT, from 234 (208-296) and 202 (178-238) sec, respectively, at 9 mEq/L, to >600 sec at 15 mEq/L (pConclusions:Citric acid infusions determine acidification and anticoagulation of blood similar to lactic acid and sodium citrate, respectively.
- Published
- 2018
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