Group Title: Critical Care
Title: N-acetylcysteine attenuates ventilator-induced diaphragm dysfunction in rats
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 Material Information
Title: N-acetylcysteine attenuates ventilator-induced diaphragm dysfunction in rats
Series Title: Critical Care
Physical Description: Archival
Creator: Agten,A.
Powers,S. K.
Publication Date: 2010
General Note: Start pageP203
General Note: M3: 10.1186/cc8435
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Bibliographic ID: UF00099882
Volume ID: VID00001
Source Institution: University of Florida
Holding Location: University of Florida
Rights Management: Open Access:
Resource Identifier: issn - 1364-8535


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Critical Care 2010, Volume 14 Suppl 1

decreased in the CMV and the low MP group (-18%, P <0.05 vs C) but its
level was preserved to control levels in the high MP group. Analysis of the
caspase-3 mediated cleavage of a -spectrin revealed that CMV induced
a i 11,I ... rise in caspase-3 activity when compared with C (+194%,
P <0.001). Caspase-3 activity was similarly increased in the MP-5 and the
MP- q ii (+96% and +78% respectively, P <0.05 vs C) but this increase
was i ...i 11i less compared with that of CMV. i ii11 ... negative
correlations were found between calpain activity and diaphragm force
(-0.50 -0.57, P <0.02). i i ii ... positive correlations were observed between
calpastatin and diaphragm force (0.43 and CSA of the type IIx/b fibers (r 0.57, P <0.02).
ConclusionsThe ability ofcorticosteroids to protect against CMV-induced
diaphragmatic contractile dysfunction and atrophy are dose dependent
with only high doses of corticosteroids providing protection.
Acknowledgements Supported by Astra Zeneca Pharmaceuticals and
1, Makes etal.:AmJ Respi Crit Care Med 2008,178:1219-1226,

Alveolar recruitment with non-invasive mechanical ventilation
(C-PAP) in patients with nonobstructive respiratory failure
VTomicic, R Moreno', VF i ,. ', J Keymer, A Fuentealbal,
G Hormazaball, R Perez', J Molina, J 1 1
'Clinica Alemana de Santiago, Chile; University ofSao Paulo, Brazil
Critical Care 2010, 14(Suppl 1):P202 (doi: 10.1186/cc8434)

Introduction Non-invasive mechanical ventilation (NIMV) is able to reduce
reintubation especially in patients with exacerbation of COPD. Results have
not been reached in critically ill patients with nonobstructive respiratory
failure (NORF). However, the NIMV in most of these studies has been applied
without making an effort to open the lung and adjusting the C-PAP after
opening up the lung using a clinical approach. Our aim was to evaluate the
effects of applying recruitment manoeuvres (RM) with C-PAP and titrate it
according to clinical decremental C-PAP trial in patients with NORF
Methods NORF patients for whom NIMV was indicated between January
2008 and July 2009 were included and submitted to the NIMV-RM protocol
when a trained team was available. Bi-PAP and a full face mask were used.
The inclusion criteria were at least two of the following: respiratory rate
(RR) >30, accessory muscle activity, saturation <90% with FiO >50% and
consolidation areas on thorax X-ray. Gradual increasing of C-PAP (2 cmH 0)
was used from 10 to 20 cmH20. Each level of C-PAP was sustained for 5
minutes according to tolerance. The C-PAP after RM was adjusted when
the maximal tidal volume (VT) was reached, pulse oximetry (PO) did not
show any substantial change and when the patient was comfortable.
Demographic data, APACHE II score and lung injury score (LIS) were
measured. Cardiac rate (CR), RR, arterial pressure (AP), PO, minute ventilation
(VE) and percentage of mask leak (PML) were recorded through the RM.
Arterial blood gases were measured pre-RM, 1, 12 and 24 hours after RM.
Variables are expressed as median (range). ANOVA by repeated measures or
Kruskal- Wallis was used, P <0.05 was considered i i,, ...i
Results Fourteen patients were included. Age, APACHE II and LIS were: 56
(17 to 80); 14 (4 to 21) and 2 (1.3 to 2.7). The PaO /FiO2 ratio increased from
169.1 +69.7 (basal) to 261 + 106 after I hour ofRM (P 0.02).Improvement
was preserved at 12 and 24 hours, 280 + 69 and 295 + 73, respectively. The
C-PAP level 1 hour after RM was 14.9 + 2.4, and 14.1 + 1.9 at 24 hours post
RM.The hemodynamic stability, RR, AP, PML and VE did not change during
and after the RM.
Conclusions RM with gradual increments of C-PAP is safe. RM in patients
with NORF could be an alternative to rescue patients with poor outcome
with NIMV alone.

N-acetylcysteine attenuates ventilator-induced diaphragm
dysfunction in rats
A Agten', K Maes', A Smuder2, SK Powers2, M Decramer',
G Gayan-Ramirez'
'KU Leuven, Belgium; 2University of Florida, Gainesville, FL, USA
Critical Care 2010, 14(Suppl 1):P203 (doi: 10.1186/cc8435)

Introduction Controlled mechanical ventilation (CMV) results in
diaphragmatic dysfunction. Oxidative stress is an important contributor
to ventilator-induced diaphragm dysfunction, since 18 hours of CMV
lead to increased protein oxidation and increased lipid peroxidation. We
hypothesized that administration of an antioxidant, N-acetylcysteine
(NAC), would restore the redox balance in the diaphragm and prevent the
deleterious effects of CMV
Methods Anesthetized rats were submitted for 24 hours to either spon-
taneous breathing while receiving 150 mg/kg NAC (SBNAC) or saline
(SBSAL) or to CMV while receiving 150 mg/kg NAC (MVNAC) or saline
Results After 24 hours, diaphragm forces were i i,,, ....i1 lower in
MVSAL compared with all groups. Administration of NAC completely
abolished this decrease such that forces produced in the MVNAC group
were comparable with those of both SB groups. Protein oxidation was
i ii11 ...ii increased in MVSAL (+53%, P <0.01) and was restored in
MVNAC. '*1 1i i1, i caspase-3 activity was iii ...ii increased in
MVSAL compared with SBSAL (+279%, P <0.001). Caspase-3 activity
was also increased in the MVNAC group (+158.5%, P <0.01) but to a
i iii ... lesser extent compared with that of MVSAL. Calpain activity
was ii-1, ...ii increased after CMV (+137%, P <0.001 vs SBSAL), while
it was similar to SB groups in the MVNAC group. i iii -... negative
correlation was found between calpain activity and diaphragm tetanic
force (r- -0.48, P= 0.02).
Conclusions These data show that the administration of NAC was able to
preserve the ii i ii , i from the deleterious effects of CMV NAC inhibits
the increase in oxidative stress and proteolysis and reduces the decrease
in force generating capacity of the diaphragm.

In vitro muscle contraction force measurements on isolated and
entire rat diaphragms
C Armbruster, C Dassow, KGamerdinger, J Guttmann, M Schneider,
S Schumann
University Medical Center Freiburg, Germany
Critical Care 2010, 14(Suppl 1):P204 (doi: 10.1186/cc8436)

Introduction Inactivity of the diaphragmatic muscles during mechanical
ventilation leads to atrophy and contractile dysfunction. Up to now, in
vitro force measurements were performed only on single diaphragmatic
muscle strips. Our intention was to find out how mechanical and electrical
stimulation influences the condition of the diaphragm as a whole organ.
To determine the status of the diaphragm, muscle contraction forces were
measured on entire rat diaphragms.
Methods We used an earlier described bioreactor [1] as the cultivation
and measurement device for the whole rat ii i,, i... The bioreactor
consists of a pressure chamber and a supply chamber that are separated
by a very flexible and soft membrane [2]. On this membrane the sample
diaphragm is placed. By application of certain gas volumes (0 to 1.5 ml)
in the pressure chamber, diaphragms are deflected to various levels of
pretension. ', i| i i 1... were electrically stimulated at each deflection
level 10 times (750 ms duty cycle, 100 ms stimulation time, 5 ms pulse
width, 200 Hz frequency). Pressure changes caused by muscle contraction
were recorded inside the pressure chamber and muscle contraction
forces were calculated. After initial force measurements, diaphragms were
exposed for 6 hours to one of four different treatments: nonstimulated
storage (control), cyclic mechanical deflection, electrical stimulation every
20 minutes, combination of cyclic deflection and electrical stimulation.
After 6 hours another force measurement was performed. Supernatants
were collected after 6 hours and investigated for IL 6 activity.
Results I 11i, i on the level of deflection of the i I ii' 1 muscle
contraction force increased from 0.1 N (volume 0.6 ml) to 0.7 N (volume
1.5 ml). A larger pretension of the diaphragm resulted in larger muscle
contraction force. After treatment, muscle contraction force decreased in
all groups. Muscle contraction force was smallest in the passive control
group (0.05 N), larger and similar in the electrically stimulated (0.1 N) and
combination (0.09 N) groups and largest in the mechanically deflected
group (0.15 N). IL 6 activity increased after 6 hours of treatment.
Conclusions We conclude that it is possible to perform force
measurements on whole rat diaphragms in our in vitro model. Additionally,
the diaphragms can kept alive for >6 hours to apply different stimulation

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