Oral Presentation Room S UNDAY O CTOBER TH Pathophysiology of by puffdaddy


									Oral Presentation                                                                                                         Room 5.2c - 08:30-10:30

                                                   S UNDAY, O CTOBER 5 TH 2008

                                                                           40. Pathophysiology of acute lung injury

                                                                        The impact of bone marrow stem cells therapy in pulmonary and
                                                                        extrapulmonary acute lung injury
                                                                        Indianara Araujo 1 , Soraia Abreu 1 , Fernanda Cruz 1 , Livia Fujisaki 1 , Luiz
                                                                        Felipe Prota 1 , Debora Ornellas 1 , Cristiane Baez-Garcia 1 ,
                                                                        Hugo Castro-Faria-Neto 2 , Edwin Parra 3 , Walcy Teodoro 3 , Vera Capelozzi 3 ,
                                                                        Carlos Peres da Costa 4 , Paolo Pelosi 5 , Marcelo Morales 1 , Patricia Rocco 1 .
                                                                          Carlos Chagas Filho Biophysics Institute, Federal University of Rio de Janeiro,
                                                                        Rio de Janeiro, Brazil; 2 Laboratory of Immunopharmacology, FIOCRUZ, Rio de
                                                                        Janeiro, Brazil; 3 Department of Pathology, University of Sao Paulo, Sao Paulo,
                                                                        Brazil; 4 Laboratory of Cardiopulmonar Physiology, Federal University of
                                                                        Pernambuco, Recife, Brazil; 5 Department of Ambient, Health and Safety,
                                                                        University of Insubria, Varese, Italy

                                                                        This study test the hypothesis that bone marrow mononuclear cell (BMMC) therapy
                                                                        may have different effects in a model of pulmonary (p) and extrapulmonary (exp)

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Oral Presentation                                                                                                                                   Room 5.2c - 08:30-10:30

                                                                    S UNDAY, O CTOBER 5 TH 2008

acute lung injury (ALI) with similar mechanical compromise at the early phase of                173
the lesion. C57Bl/6 mice were divided into 8 groups (n=7/each). In Cp and Cexp                  Crackle sound analysis in a porcine ARDS model to create a non-invasive
groups, saline was intratracheally (it, 0.05 ml) or intraperitoneally (ip, 0.5 ml)              recruitment monitoring
given. In ALIp and ALIexp groups, mice received E. coli lipopolysaccharide (LPS,                Stephan J. Schließmann 1 , Knut Möller 2 , Yu Lu 2 , Giskard Wagner 1 ,
40 mg it or 400 mg ip, respectively). 6-hours after saline or LPS administration,               Josef Guttmann 1 . 1 Department for Anaesthesiology and Intensive Care Medicine,
we intravenously injected either BMMC (2x106 ) or an equal volume of saline. At                 Experimental Anaesthesiology, University Hospital Freiburg, Freiburg, Germany;
1 week, lung mechanics (static elastance, and resistive and viscoelastic pressures),              Biomedical Engineering, Furtwangen University, Villingen-Schwenningen,
collagen fibre content, and the rate of epithelial apoptosis were higher in ALIp than            Germany
ALIexp groups. Histological analysis (light, confocal and electronic microscopies)
showed extensive injury of alveolar epithelium and intact capillary endothelium in              Mechanical ventilation is often implemented in therapy of acute respiratory dis-
ALIp, whereas ALIexp group presented endothelial lesion and interstitial edema.                 tress syndrome (ARDS). To reduce both ventilator-associated lung injury and
BMMC attenuated lung mechanics, tissue cellularity, the amount of atelectasis,                  atelectasis, it is necessary to determine an ideal positive end-expiratory pressure
and lung epithelial apoptosis more in ALIexp than in ALIp, but reduced collagen                 (PEEP), which highly depends on the recruitment state of the lung. To monitor and
fibre content similarly in both groups. In conclusion, BMMC therapy may be                       to quantify intratidal recruitment processes we recorded intrapulmonary crackle
effective at inhibiting fibrogenesis independent of the aetiology of ALI, but its                sounds with a newly developed sound recording system.
beneficial effects on inflammatory response and lung mechanics vary according to                  Adult porcine lungs were isolated right after usual slaughter. A tube was closely
the cause of ALI. The higher permeability of the alveolar-capillary membrane in                 stitched off in left main bronchus. Lungs were wetly transported in steady at-
ALIexp may facilitate the engraftment of bone marrow stem cells contributing to                 electatic state and were recruited via low flow manoeuvre (LFM). Sounds were
the better functional and morphological effect.                                                 recorded by using a standard stethoscope with an integrated low noise microphone
Supported by: PRONEX-FAPERJ, FAPERJ, CNPq.                                                      laid down directly on the moisturized viceral pleura while first inflation. A second
                                                                                                recruiting manoeuvre was started after 3 ventilation-free hours.
                                                                                                Recruitment sounds could be identified and analysed in the recorded sound data.
171                                                                                             Power of the sound signal was determined in a specific frequency range for crackles
Effect of activated protein C on cell contraction of human alveolar epithelial                  (700-900 Hz). Trains of crackles were found during the LFMs. Crackles found at
cells subjected to thrombin                                                                     the beginning of the LFM increased in intensity with pressure. During the LFMs
Ferranda Puig 1,6 , Melanie Adda 1,6 , Octavi Marti-Sistac 2,6 , Daniel Navajas 3,4,6 ,         the sound energy shows a Gaussian shape which correlates well to the predictions
Ramon Farre 3,5,6 , Antoni Artigas 1,6 . 1 Critical Center, Sabadell Hospital,                  of the Hickling model. Recruitment of long-time atelectatic lungs induces higher
Sabadell, Spain; 2 IUFPT-UAB Institut Universitari, Fundació Parc Taulí-UAB,                    intensity then recruitment of short-time atelectatic lungs.
Sabadell, Spain; 3 Unitat de Biofísica i Bioingenyeria, Universitat de Barcelona,               This approach may be considered as a first step to online monitoring of recruitment
Barcelona, Spain; 4 Institut de Bioenginyeira de Catalunya, IBEC, Barcelona,                    processes in the pulmonary system.
Spain; 5 IDIBAPS, IDIBAPS, Barcelona, Spain; 6 CIBER de Enfermedades                            References:
Respiratorias, CIBERES, Bunyola, Spain                                                          1. Gattinoni L et al., N Engl J Med, 354(17), 2006
                                                                                                2. Peták F et al., Eur Respir J, 27(4), 2006.
Background: Contraction of alveolar epithelial cells can play an important role
to maintain the structural integrity of the alveolar epithelium which is regulated
by the balance between centripetal forces and cell-cell and cell-matrix tethering               174
forces. Proteins of the coagulation cascade such as Thrombin (THR), that con-                   Open lung positive end-expiratory pressure (PEEP) titration by respiratory
tracts alveolar epithelial cells (AEC), or Activated Protein C (APC), an endothelial            system input reactance (Xrs)
barrier-protective agent, could modulate this balance of forces.                                Raffaele Dellaca’ 1 , Marie Andersson-Olerud 2 , Emanuela Zannin 1 , Peter Kostic 2 ,
Aim: To study the effects of THR and APC on the contraction of alveolar epithelial              Pasquale Pompilio 1 , Marlen Romano’ 1 , Sonia Bernardinello 1 , Antonio Pedotti 1 ,
cells by means of traction microscopy (TM).                                                     Peter Frykholm 2 , Goran Hedenstierna 3 . 1 Biomedical Engineering Department,
Methods: Two days before TM measurements, AEC were platted on collagen-I                        Politecnico di Milano University, Milano, Italy; 2 Department of Surgical
coated polyacrylamide gels with embedded fluorescent microbeads (200 nm). On                     Sciences, Section of Anaesthesiology, Uppsala University, Uppsala, Sweden;
the day of experiments, cells were incubated for 3 h with APC (50 μg/ml) or                     3
                                                                                                  Department of Medical Sciences, Clinical Physiology, Uppsala Univesrity,
vehicle (control) (N=10). Fluorescence images of the surface of the gel were                    Uppsala, Sweden
taken to assess the distribution of beads both during baseline, and 5 and 10 min
after addition of thrombin (0.5 U/ml). At the end of the challenge, cells were                  The use of PEEP has been shown to be effective in reducing atelectasis and reduc-
detached with trypsin and a fluorescence image of the relaxed gel was acquired.                  ing morbidity and mortality in acute lung injury. However, a non-invasive tool to
The corresponding total force (F) exerted by the cell on the substrate was then                 identify the optimal open-lung PEEP (PEEPol) is still unavailable. We investigated
computed.                                                                                       the sensitivity of an index (Cx5=-1/Xrs) derived from Xrs at 5Hz in identify lung
Results: In controls, baseline F was 79.5±21.7 nN. THR induced a significant                     collapse during a decremental PEEP trial in 5 ventilated piglets (volume control,
increase in F at 5 min (160.6±31.9 nN) and at 10 min (170.0±31.4). The increase                 Vt=6 mL/kg) after repeated broncho-alveolar lavages. During the trial, PEEP was
in the traction forces exerted by the cells was mainly experienced at the cell                  reduced every 6 min by 2 cmH2O from 24 cmH2O. Before changing PEEP, PaO2,
periphery. APC significantly reduced the THR-induced increase in F at 5 min                      Cx5 and CT scans were measured. During the trial, Cx5 increased with decreasing
(79.0±15.3 nN) and at 10 min (78.6±15.0 nN).                                                    PEEP to a maximum (Cx5max) or a plateau, than suddenly decreased. Lung
Conclusions: These data may contribute to interpret the protective effect of APC                collapse was identified as the first step in which Cx5 decreased more than 10% of
in Acute Lung Injury.                                                                           Cx5max. PEEPol was consequently defined as the level of PEEP preceding the lung
                                                                                                collapse and compared with Pao2 and the percentage of non- and poorly-aerated
                                                                                                tissue computed from CT scans (see figure, representative animal).
Mechanical ventilation in healthy lungs and micromechanics: increase in
tissue elastance and resistance in the non dependant lung within 30 min
Christiane C. Calciolari 3 , Vivien S. Piccin 3 , Tatiana Lanças 3 , Kelly Yoshizaki 1 ,
Susimeire Gomes 1 , Denise Frediani-Barbeiro 1 , Marisa Dolhnikoff 3 , Elnara
M. Negri 1,2 . 1 LIMs 9, 20 and 51, University of Sao Paulo, Sao Paulo, Brazil;
  Nucleo Avançado de Torax, Sirio Libanês Hospital, Sao Paulo, Brazil;
  Pathology, University of Sao Paulo, Sao Paulo, Brazil

Mechanical ventilation is a useful tool to sustain life in cases of respiratory failure
or in healthy subjects, during anesthesia. Nevetheless, it represents a source of in-
jury and a potent stimuli for fibrogenesis mediated by mechanotransduction. There
has been a crescent body of evidence supporting ventilation induced lung injury
(VILI) mediated by high pressure, high volume and/or absence of PEEP. It is known
that non dependent lung regions may suffer early damages during MV. The aim of
the present work was to verify if short term MV could induce regional differences
in peripheral lung tissue mechanics. New Zealand rabbits were ventilated for 30
min in suppine position with Vt 10 ml/kg, PEEP=5 cm H2O, Flow=2l/min, RR=
30 rpm, and FiO2= 40%. Subpleural strips were obtained from dependent (d) and
non dependent (nd) left lung for micromechanics analysis. Tissue elastance (E) and
resistance (R) showed significant differences: Ed= 38152,13±11947,51 and End=                    In average, PEEPol was 12±2SD cmH2O. At this PEEP, PaO2 decreased by
100923,6±18890,34 (p=0,028); Rd= 966,50±292,46 and Rnd= 2508,32±384,98                          only 3.2±3.7SD% from maximum, while it decreased by 23.4±16.3SD% on the
(p=0,018). The present work provides evidence of early disturbances of peripheral               following steps, confirming that Cx5 identified the beginning of lung collapse.
lung tissue structure submmited to mechanical ventilation even at conventional                  This was also in agreement with CT data. In conclusion, Cx5 could be useful for
parameters, frequently used during general anesthesia.                                          identifying the PEEP value that prevents end-expiratory collapse and minimises

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Oral Presentation                                                                                                                              Room 5.2c - 08:30-10:30

                                                                S UNDAY, O CTOBER 5 TH 2008

175                                                                                         tilation. This is a physiologic study aimed at comparing the effects of different
Serum inflammatory response during weaning from mechanical ventilation                       levels of assistance with PSV and NAVA on arterial blood gases (ABGs), breathing
Jacobo Sellares 1,4 , Miquel Ferrer 1,4 , Hugo Loureiro 1,4 , Xavier Filella 2 ,            pattern (BP), and asynchrony index (AI).
Cristina Esquinas 1,4 , Raquel Piner 1,4 , Ramon Farre 3,4 , Antoni Torres 1,4 .            Methods: We studied 14 sedated, intubated and mechanically ventilated patients.
  Respiratory Intensive Care Unit, Hospital Clínic, Barcelona, Spain; 2 Servei de           PSV and NAVA baseline levels (PSV100 and NAVA100) were matched, then
Bioquimica Clinica, Hospital Clínic, Barcelona, Spain; 3 Unitat de Biofisica i               decreased (PSV50 and NAVA50) and increased (PSV150 and NAVA150) by 50%
Bioenginyeria, Facultat de Medicina. Universitat de Barcelona-IDIBAPS,                      to set 6 levels of assistance. ABGs, Tidal Volume/kg (VT/kg), respiratory rate
Barcelona, Spain; 4 CIBER, Enfermedades respiratorias, Mallorca, Spain                      (RR), and AI were assessed.
                                                                                            Results: The difference in ABGs was not statistically significant either between the
Rationale: Among the pathophysiological mechanisms related to weaning out-                  2 modes and between the 3 levels of assistance. VT/kg showed no difference with
come, the role of systemic inflammatory response is unknown.                                 the 2 modes at 2 lower levels of assistance; on the contrary, VT/kg was significantly
Objectives: To assess the course of different systemic inflammatory mediators                higher with PSV150 (9.1±2.2 ml/kg), as opposed to NAVA150 (7.1±2 ml/kg)
during withdrawal of mechanical ventilation in a mixed population.                          (p<0.001). Accordingly, RR was significantly lower with PSV150, compared to
Methods: A prospective clinical study was conducted in mechanically-ventilated              NAVA150. With NAVA, no asynchrony event was observed in any patient, while
patients. 30-min spontaneous breathing trials (n=29) were performed in 26 patients.         with PSV an AI > 10% was found in 36% of the patients.
Blood samples were drawn before and at the end of the trial. An additional sample           Conclusion: NAVA improved patient-ventilator interaction, while reducing the
was also drawn 24 hours later in a subset of patients.                                      risk of over-assistance.
Measurements and Main Results: Serum levels of interleukin-6 increased
from mechanical ventilation to spontaneous breathing in the overall population
(p=0.003), but did not discriminate between weaning failure and success. In the
subgroup of chronic obstructive pulmonary disease patients, serum interleukin-6
increased from mechanical ventilation to spontaneous breathing in those who
failed the weaning attempt (p=0.03), while these levels remained unchanged in
those who tolerated spontaneous breathing. Moreover, in 3 extubated patients
who subsequently developed respiratory failure after extubation, serum levels of
interleukin-6 tended to increase 24 hours after extubation (p=0.11).
Conclusions: Increased systemic inflammatory response is associated to sponta-
neous breathing failure in ventilated patients with chronic obstructive pulmonary
disease. The potential utility of interleukin-6 to predict respiratory failure after
extubation warrants further studies in larger populations.
Supported by Ministerio de Sanidad y Consumo (FIS-PI040929 and CibeRes-
CB06/06/0028) and Ministerio de Ciencia y Tecnología (SAF2005-0110).

Exhaled nitric oxide in brain-injured, mechanically ventilated patients with
no acute lung injury or sepsis
Ioanna Korovesi 1 , Evangellos Papadomichelakis 2 , Anastasia Kotanidou 3 ,
Christina Sotiropoulou 1 , Antonia Koutsoukou 3 , Ioanna Dimopoulou 2 ,
Apostolos Armaganidis 2 , Charis Roussos 3 , Nandor Marczin 4 ,
Stylianos Orfanos 2 . 1 M.Simou Lab., University of Athens, Athens, Greece; 2 2nd
Critical Care Dept., Attikon Hospital, Haidari, Athens, Greece; 3 1st Critical Care
Dept., Evangelismos Hospital, Athens, Greece; 4 Dept. of Anaesthetics, Imperial
College London, London, United Kingdom

Severely brain injured patients on mechanical ventilation (MV) exhibit: (i) abnor-
mal lung mechanics and pulmonary endothelial alterations that get attenuated by
PEEP, and (ii) exhaled breath condensate-identified lung inflammation, even in the
absence of acute lung injury or sepsis (1). To test the hypothesis that such lung
inflammatory process can be detected and quantified by an established non-invasive
index of airway inflammation, namely exhaled nitric oxide (eNO) (2), we have
extended our studies to assess the eNO profile of these patients.
27 patients were ventilated with 8 ml/kg tidal volume and were placed either
on PEEP= 0 (ZEEP group, n=12) or 8 cm H2 O (PEEP group, n=15). eNO was
measured by chemiluminescense (LR1800 analyzer, Logan Research, Rochester,
Kent, UK) on MV days 1, 3 and 5; peak eNO concentration and the area under
the NO concentration-time curve (AUC) were recorded. NO was detected in the
exhaled air of all patients. In both groups, eNO peak significantly increased on
days 3 and 5 as compared to day 1, while the AUC was significantly higher on
day 3 compared to day 1 (p<0.05, by two way ANOVARM for both indices).
Throughout the measured period eNO values under PEEP were slightly higher
than values under ZEEP, however there were no significant differences between
the groups.
In conclusion, the duration of mechanical ventilation in our patients is associated
with increases in eNO evolution implying an on-going inflammatory process; these
increases tended to be higher under PEEP, probably suggesting the contribution of
a stretch-related airway mechanism.
1. I Korovesi et al. Eur Respir J 30(supp.51):444s, 2007
2. Kharitonov SA et al. Chest 130:1541, 2006.

Physiologic comparison of pressure support ventilation and neurally adjusted
ventilatory assist at different levels of assistance
Davide Colombo, Gianmaria Cammarota, Valentina Bergamaschi, Marta De
Lucia, Francesco Della Corte, Paolo Navalesi. Intensive Care Unit, Maggiore
Hospital–Piemonte Orientale University, Novara, Italy

Introduction: Neurally Adjusted Ventilatory Assist (NAVA) is a new mode of
ventilation wherein pressure is applied in proportion to electrical activity of the
diaphragm (EAdi). Because ventilator functioning is under control of the patient’s
respiratory drive, compared to Pressure Support Ventilation (PSV), NAVA should
improve patient-ventilator interaction and minimize the risk of over-assistance
(>8ml/kg). Because of sedatives, however, NAVA might induce alveolar hypoven-

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