Stefano Tredici

University of Michigan, Ann Arbor, Michigan, United States

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Publications (23)61.32 Total impact

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    ABSTRACT: Using a rabbit model of total liquid ventilation (TLV), and in a corresponding theoretical model, we compared nine tidal volume-respiratory rate combinations to identify a ventilator strategy to maximize gas exchange, while avoiding choked flow, during TLV. Nine different ventilation strategies were tested in each animal (n = 12): low [LR = 2.5 breath/min (bpm)], medium (MR = 5 bpm), or high (HR = 7.5 bpm) respiratory rates were combined with a low (LV = 10 ml/kg), medium (MV = 15 ml/kg), or high (HV = 20 ml/kg) tidal volumes. Blood gases and partial pressures, perfluorocarbon gas content, and airway pressures were measured for each combination. Choked flow occurred in all high respiratory rate-high volume animals, 71% of high respiratory rate-medium volume (HRMV) animals, and 50% of medium respiratory rate-high volume (MRHV) animals but in no other combinations. Medium respiratory rate-medium volume (MRMV) resulted in the highest gas exchange of the combinations that did not induce choke. The HRMV and MRHV animals that did not choke had similar or higher gas exchange than MRMV. The theory predicted this behavior, along with spatial and temporal variations in alveolar gas partial pressures. Of the combinations that did not induce choked flow, MRMV provided the highest gas exchange. Alveolar gas transport is diffusion dominated and rapid during gas ventilation but is convection dominated and slow during TLV. Consequently, the usual alveolar gas equation is not applicable for TLV.
    ASAIO journal (American Society for Artificial Internal Organs: 1992) 07/2009; 55(4):373-81. DOI:10.1097/MAT.0b013e3181a793b5 · 1.39 Impact Factor
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    ABSTRACT: During the 6th International Symposium on Perfluorocarbon Application and Liquid Ventilation, a round table discussion on bioengineering was held in which different experts shared their opinions and experiences about the use of a total liquid ventilator design for clinical applications. To structure the discussion, all experts were invited to contribute their knowledge within the context of three matrixes related to the liquid ventilators: 1) function and technology, 2) ventilation modes, and 3) risk analyses. The outcome of this international conference recommends continued development of a total liquid ventilator toward clinical applications.
    ASAIO journal (American Society for Artificial Internal Organs: 1992) 04/2009; 55(3):206-8. DOI:10.1097/MAT.0b013e318199c167 · 1.39 Impact Factor
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    ABSTRACT: Negative pressure generated during the expiratory phase of total liquid ventilation (TLV) may induce airway collapse. Evaluation of the effect of repeated airway collapse is crucial to optimize this technique. A total of 24 New Zealand White rabbits were randomly divided into four groups. Ventilation was performed for 6 hours with different strategies: conventional gas ventilation, TLV without airway collapse, and TLV with collapse induced in either 75 or 150 sequential breaths. In the treated groups, airway collapse was induced by increasing the perfluorocarbon drainage velocity while maintaining the minute ventilation constant. Airway pressure, gas exchange, and blood pressure were monitored at 30-minute intervals. At the end of the experiment, airway and lung parenchyma specimens were processed for light microscopy. No evidence of fluorothorax was noticed in any of the four groups at autopsy examination. Minimal signs of inflammation were noticed in all airway and lung parenchyma specimens, but no evident structural alteration was visible. Adequate gas exchange and systemic blood pressure were maintained during all the studies. Repeated airway collapse is not associated with structural changes in the respiratory system and does not alter the gas exchange ability of the lungs.
    ASAIO journal (American Society for Artificial Internal Organs: 1992) 01/2007; 53(5):549-55. DOI:10.1097/MAT.0b013e318148449d · 1.39 Impact Factor
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    ABSTRACT: The effect of viscosity on the distribution of perfluorocarbon instilled into the lungs for liquid ventilation was investigated. Perfluorocarbon (either perfluorodecalin or FC-3283) was instilled into the trachea during ventilation at a constant infusion rate of 40 ml/min and radiographic images were obtained at 30 frames/s. Image analysis was performed and the homogeneity index of the distribution was computed for images at the end of inspiration of each breath to evaluate the evolution of perfluorocarbon distribution during filling. The higher viscosity perfluorocarbon (perfluorodecalin) resulted in a more homogeneous distribution. This was attributed to perfluorodecalin's higher propensity to form liquid plugs in large airways and to those plugs leaving behind a thicker liquid layer as they propagated through the lungs.
    Journal of Biomechanical Engineering 01/2007; 128(6):857-61. DOI:10.1115/1.2354214 · 1.75 Impact Factor
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    ABSTRACT: An abstract is unavailable. This article is available as HTML full text and PDF.
    ASAIO Journal 06/2006; 52(4):491. DOI:10.1097/00002480-200607000-00033 · 1.39 Impact Factor
  • ASAIO Journal 01/2006; 52(2). DOI:10.1097/00002480-200603000-00284 · 1.39 Impact Factor
  • ASAIO Journal 01/2006; 52(4). DOI:10.1097/00002480-200607000-00043 · 1.39 Impact Factor
  • ASAIO Journal 01/2006; 52(2):65A. DOI:10.1097/00002480-200603000-00274 · 1.39 Impact Factor
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    ABSTRACT: Flow limitation in liquid-filled lungs is examined in intact rabbit experiments and a theoretical model. Flow limitation ("choked" flow) occurs when the expiratory flow reaches a maximum value and further increases in driving pressure do not increase the flow. In total liquid ventilation this is characterized by the sudden development of excessively negative airway pressures and airway collapse at the choke point. The occurrence of flow limitation limits the efficacy of total liquid ventilation by reducing the minute ventilation. In this paper we investigate the effects of liquid properties on flow limitation in liquid-filled lungs. It is found that the behavior of liquids with similar densities and viscosities can be quite different. The results of the theoretical model, which incorporates alveolar compliance and airway resistance, agrees qualitatively well with the experimental results. Lung compliance and airway resistance are shown to vary with the perfluorocarbon liquid used to fill the lungs. Surfactant is found to modify the interfacial tension between saline and perfluorocarbon, and surfactant activity at the interface of perfluorocarbon and the native aqueous lining of the lungs appears to induce hysteresis in pressure-volume curves for liquid-filled lungs. Ventilation with a liquid that results in low viscous resistance and high elastic recoil can reduce the amount of liquid remaining in the lungs when choke occurs, and, therefore, may be desirable for liquid ventilation.
    Journal of Biomechanical Engineering 09/2005; 127(4):630-6. DOI:10.1115/1.1934099 · 1.75 Impact Factor
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    ABSTRACT: The effects of end-inspiratory lung volume (EILV) and expiratory flow rate (Q) on the location of flow limitation in liquid-filled lungs were investigated by measuring pressure along the airways and by radiographic imaging. The lungs of New Zealand white rabbits were filled with perfluorocarbon to the randomly selected EILV of 20, 30, or 40 ml/kg, and the volume was actively drained at one of three Q: 2.5, 5.0, or 7.5 ml/s. The minimum pressures recorded by a movable catheter at locations along the airways show that flow limitation occurred in the main bronchi and trachea, and was independent of EILV and Q. The minimum pressure at the trachea was -80 mm Hg compared with values that were more positive than -10 mm Hg at a location 3 cm distal to the carina for all EILV and Q combinations. This location was confirmed by the lung images. The airway diameters gradually decreased with time, until flow limitation occurred. In airways distal to the collapse, there was not a significant decrease in diameter. Based on these data, we conclude that flow limitation in liquid-filled lungs occurs in the trachea and main bronchi and its location is independent of EILV or Q.
    ASAIO Journal 01/2005; 51(6):781-8. DOI:10.1097/01.mat.0000179252.02471.9e · 1.39 Impact Factor
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    ABSTRACT: Flow limitation during pressure-driven expiration in liquid-filled lungs was examined in intact, euthanized New Zealand white rabbits. The aim of this study was to further characterize expiratory flow limitation during gravitational drainage of perfluorocarbon liquids from the lungs, and to study the effect of perfluorocarbon type and negative mouth pressure on this phenomenon. Four different perfluorocarbons (PP4, perfluorodecalin, perfluoro-octyl-bromide, and FC-77) were used to examine the effects of density and kinematic viscosity on volume recovered and maximum expiratory flow. It was demonstrated that flow limitation occurs during gravitational drainage when the airway pressure is < or = -15 cm H(2)O, and that this critical value of pressure did not depend on mouth pressure or perfluorocarbon type. The perfluorocarbon properties affect the volume recovered, maximum expiratory flow, and the time to drain, with the most viscous perfluorocarbon (perfluorodecalin) taking the longest time to drain and resulting in lowest maximum expiratory flow. Perfluoro-octyl-bromide resulted in the highest recovered volume. The findings of this study are relevant to the selection of perfluorocarbons to reduce the occurrence of flow limitation and provide adequate minute ventilation during total liquid ventilation.
    ASAIO Journal 01/2005; 51(6):795-801. DOI:10.1097/01.mat.0000186127.36070.40 · 1.39 Impact Factor
  • ASAIO Journal 01/2005; 51(2). DOI:10.1097/00002480-200503000-00201 · 1.39 Impact Factor
  • ASAIO Journal 01/2005; 51(2). DOI:10.1097/00002480-200503000-00213 · 1.39 Impact Factor
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    ABSTRACT: A functional total liquid ventilator should be simple in design to minimize operating errors and have a low priming volume to minimize the amount of perfluorocarbon needed. Closed system circuits using a membrane oxygenator have partially met these requirements but have high resistance to perfluorocarbon flow and high priming volume. To further this goal, a single piston prototype ventilator with a low priming volume and a new high-efficiency hollow-fiber oxygenator in a circuit with a check valve flow control system was developed. Prospective, controlled animal laboratory study. Research facility at a university medical center. Seven anesthetized, paralyzed, normal New Zealand rabbits The prototype oxygenator, consisting of cross-wound silicone hollow fibers with a surface area of 1.5 m2 with a priming volume of 190 mL, was tested in a bench-top model followed by an in vivo rabbit model. Total liquid ventilation was performed for 3 hrs with 20 mL.kg(-1) initial fill volume, 17.5-20 mL.kg(-1) tidal volume, respiratory rate of 5 breaths/min, inspiratory/expiratory ratio 1:2, and countercurrent sweep gas of 100% oxygen. Bench top experiments demonstrated 66-81% elimination of CO2 and 0.64-0.76 mL.min(-1) loss of perfluorocarbon across the fibers. No significant changes in PaCO2 and PaO2 were observed. Dynamic airway pressures were in a safe range in which ventilator lung injury or airway closure was unlikely (3.6 +/- 0.5 and -7.8 +/- 0.3 cm H2O, respectively, for mean peak inspiratory pressure and mean end expiratory pressure). No leakage of perfluorocarbon was noted in the new silicone fiber gas exchange device. Estimated in vivo perfluorocarbon loss from the device was 1.2 mL.min(-1). These data demonstrate the ability of this novel single-piston, nonporous hollow silicone fiber oxygenator to adequately support gas exchange, allowing successful performance of total liquid ventilation.
    Critical Care Medicine 11/2004; 32(10):2104-9. DOI:10.1097/01.CCM.0000142701.41679.1B · 6.15 Impact Factor
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    ABSTRACT: Motivated by the goal of understanding how to most homogeneously fill the lungs with perfluorocarbon for liquid ventilation, we investigate the transport of liquid instilled into the lungs using an intact rabbit model. Perfluorocarbon is instilled into the trachea of the ventilated animal. Radiographic images of the perfluorocarbon distribution are obtained at a rate of 30 frames/s during the filling process. Image analysis is used to quantify the liquid distribution (center of mass, spatial standard deviation, skewness, kurtosis, and indicators of homogeneity) as time progresses. We compare the distribution dynamics in supine animals to those in upright animals for three constant infusion rates of perfluorocarbon: 15, 40, and 60 ml/min. It is found that formation of liquid plugs in large airways, which is affected by posture and infusion rate, can result in a more homogeneous liquid distribution than gravity drainage alone. The supine posture resulted in more homogeneous filling of the lungs than did upright posture, in which the lungs tend to fill in the inferior regions first. Faster instillation of perfluorocarbon results in liquid plugs forming in large airways and, consequently, more uniform distribution of perfluorocarbon than slower instillation rates in the upright animals.
    Journal of Applied Physiology 06/2004; 96(5):1633-42. DOI:10.1152/japplphysiol.01158.2003 · 3.43 Impact Factor
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    ABSTRACT: An abstract is unavailable. This article is available as HTML full text and PDF.
    ASAIO Journal 02/2004; 50(2):155. DOI:10.1097/00002480-200403000-00176 · 1.39 Impact Factor
  • ASAIO Journal 01/2004; 50(2). DOI:10.1097/00002480-200403000-00171 · 1.39 Impact Factor
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    ABSTRACT: We hypothesized that a 50% increase in respiratory system elastance (Ers) would indicate similar degree of lung damage (equi-damage, ED), independently of ventilation strategy. A prospective, randomized animal laboratory investigation at a university hospital laboratory. 35 anesthetized, paralyzed, mechanically ventilated male Sprague-Dawley rats. Each rat was ventilated with a different combination of tidal volume, positive end-expiratory pressure, and inspired fraction of oxygen. Ers was determined throughout the experiment; the studies were interrupted when Ers reached 150% (ED) of its baseline value, or after 5 h. Lung wet to dry weight ratio (W/D) was assessed. Morphological damage of the lung was scored on a grading of perivascular edema, hemorrhage, and breaks in the alveolar septa to obtain a total injury score. Twenty-four rats achieved an Ers of 150%: nine within 1 h (class 1), nine in 1-2 h (class 2), and six in 2-5 h (class 3). Eleven rats did not reach the target 50% increase in Ers (class 4). W/D was higher in rats that reached the target than in those that did not. W/D did not differ among rats that reached ED. Similarly, the total injury score did not differ among classes 1-3 but was higher than class 4. In the setting of VILI a 50% increase in Ers corresponds to an equal level of lung damage, irrespective of ventilatory setting and time of ventilation.
    Intensive Care Medicine 03/2002; 28(2):196-203. DOI:10.1007/s00134-001-1177-2 · 5.54 Impact Factor
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    ABSTRACT: To study the influence of different mechanical ventilatory support strategies on organs distal to the lung, we developed an in vivo rat model, in which the effects of different tidal volume values can be studied while maintaining other indexes. Prospective, randomized animal laboratory investigation. University laboratory of Ospedale Maggiore di Milano-Instituto di Ricovero e Cura a Carattere Scientifico. Anesthetized, paralyzed, and mechanically ventilated male Sprague-Dawley rats. Two groups of seven rats each were randomized to receive tidal volumes of either 25% or 75% of inspiratory capacity (IC), calculated from a preliminary estimation of total lung capacity. Ventilation strategies for the two groups were as follows: a) 25% IC, 9.9+/-0.8 mL/kg; frequency, 59+/-4 beats/min; positive end-expiratory pressure, 3.6+/-0.8 cm H2O; and peak inspiratory airway pressure (Paw), 13.2+/-2 cm H20; and b) 75% IC, 29.8+/-2.9; frequency, 23+/-13; positive end-expiratory pressure, 0; peak inspiratory Paw, 29.0+/-3. Mean arterial pressure (invasively monitored) remained well above adequate perfusion pressure values throughout, and no significant difference was seen between the two groups. PaO2, pHa, and PaCO2 values were compared after 60 mins of ventilation and again, no significant difference was seen between the two groups (PaO2, 269+/-25 and 260+/-55 torr; pHa, 7.432+/-0.09 and 7.415+/-0.03; PaCO2, 35.4+/-8 and 32.5+/-2 torr, for the 25% IC and 75% IC groups, respectively). Mean Paws were not different (6.4+/-0.8 cm H2O in the 25% IC groups, and 6.1+/-1.2 in the 75% IC groups, respectively). At the end of the experiment, animals were killed and the liver and kidney isolated, fixed in 4% formalin, cut, and stained for optic microscopy. Kidneys from rats ventilated with 75% IC showed increased Bowman's space with collapse of the glomerular capillaries. This occurred in a greater percentage of rats ventilated with 75% IC (0.67+/-0.2 vs. 0.29+/-0.2, 75% IC vs. 25% IC, respectively; p < .05). Perivascular edema was also present in rats ventilated with 75% IC (p < .05). Morphometric determinations of the empty zones (index of edema) demonstrated a trend toward differences between 75% IC livers and 25% IC (0.14+/-0.05 vs. 0.11+/-0.02, respectively). We conclude that it is possible to study the effects of mechanical ventilatory support on organs distal to the lung by means of an in vivo rat model.
    Critical Care Medicine 12/2000; 28(11):3697-704. DOI:10.1097/00003246-200011000-00027 · 6.15 Impact Factor
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    ABSTRACT: Morbidly obese patients, during anesthesia and paralysis, experience more severe impairment of respiratory mechanics and gas exchange than normal subjects. The authors hypothesized that positive end-expiratory pressure (PEEP) induces different responses in normal subjects (n = 9; body mass index < 25 kg/m2) versus obese patients (n = 9; body mass index > 40 kg/m2). The authors measured lung volumes (helium technique), the elastances of the respiratory system, lung, and chest wall, the pressure-volume curves (occlusion technique and esophageal balloon), and the intraabdominal pressure (intrabladder catheter) at PEEP 0 and 10 cm H2O in paralyzed, anesthetized postoperative patients in the intensive care unit or operating room after abdominal surgery. At PEEP 0 cm H2O, obese patients had lower lung volume (0.59 +/- 0.17 vs. 2.15 +/- 0.58 l [mean +/- SD], P < 0.01); higher elastances of the respiratory system (26.8 +/- 4.2 vs. 16.4 +/- 3.6 cm H2O/l, P < 0.01), lung (17.4 +/- 4.5 vs. 10.3 +/- 3.2 cm H2O/l, P < 0.01), and chest wall (9.4 +/- 3.0 vs. 6.1 +/- 1.4 cm H2O/l, P < 0.01); and higher intraabdominal pressure (18.8 +/-7.8 vs. 9.0 +/- 2.4 cm H2O, P < 0.01) than normal subjects. The arterial oxygen tension was significantly lower (110 +/- 30 vs. 218 +/- 47 mmHg, P < 0.01; inspired oxygen fraction = 50%), and the arterial carbon dioxide tension significantly higher (37.8 +/- 6.8 vs. 28.4 +/- 3.1, P < 0.01) in obese patients compared with normal subjects. Increasing PEEP to 10 cm H2O significantly reduced elastances of the respiratory system, lung, and chest wall in obese patients but not in normal subjects. The pressure-volume curves were shifted upward and to the left in obese patients but were unchanged in normal subjects. The oxygenation increased with PEEP in obese patients (from 110 +/-30 to 130 +/- 28 mmHg, P < 0.01) but was unchanged in normal subjects. The oxygenation changes were significantly correlated with alveolar recruitment (r = 0.81, P < 0.01). During anesthesia and paralysis, PEEP improves respiratory function in morbidly obese patients but not in normal subjects.
    Anesthesiology 11/1999; 91(5):1221-31. · 6.17 Impact Factor

Publication Stats

630 Citations
61.32 Total Impact Points

Institutions

  • 2004–2009
    • University of Michigan
      • • Department of Surgery
      • • Department of Biomedical Engineering
      Ann Arbor, Michigan, United States
    • Tokyo Denki University
      Edo, Tōkyō, Japan
  • 2002
    • Istituto Nazionale Tumori "Fondazione Pascale"
      Napoli, Campania, Italy
  • 1997–2000
    • University of Milan
      • Institute of Human Physiology II
      Milano, Lombardy, Italy