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Acta Cirúrgica Brasileira - Vol. 27 (2) 2012 - 109
3 – ORIGINAL ARTICLE
MODELS, BIOLOGICAL
Effects of controlled and pressure support mechanical ventilation on rat diaphragm
muscle¹
Efeitos da ventilação mecânica controlada e por pressão de suporte no músculo diafragma de
ratos
André de Sá Braga Oliveira
I
, Lívia Bandeira Costa
II
, Thiago de Oliveira Assis
III
, Diógenes Luís da Mota
IV
, Eduardo Ériko
Tenório de França
V
, José Cândido de Araújo Filho
VI
, Silvania Tavares Paz Rosas
VII
, Paloma Lys de Medeiros
VIII
I
Master, Assistant Professor of Anatomy, Integrated Colleges of Patos (ICP), Brazil. Conception and design, acquisition of data, analysis and
interpretation and histopathogical studies, manuscript writing.
II
Fellow PhD degree, Therapeutic Innovation, UFPE, Pernambuco, Brazil. Manuscript writing.
III
Master, Assistant Professor, Department of Morphology, Federal University of Paraiba (UFPB), Brazil. Conception, design and manuscript writing.
IV
Associate Professor, Department of Histology and Embriology, Federal University of Pernambuco, UFPE, Brazil. Manuscript writing, final approval.
V
Master, Assistant Professor, Catholic University of Pernambuco, Brazil. Conception and design.
VI
Expert of Public Health, Physiotherapist, Department of Physiotherapy, UFPE, Pernambuco, Brazil. Manuscript writing.
VII
Technician, Postgraduate Program in Pathology, UFPE, Pernambuco, Brazil. Acquisition of data.
VIII
MD, Associate Professor, Department of Histology and Embriology, UFPE, Pernambuco, Brazil. Analysis, interpretation, histopathogical studies
and critical revision.
ABSTRACT
PURPOSE: The objective of this study was to analyze the effects of Pressure Controlled Ventilation mode (PCV-C) and PSV mode in
diaphragm muscle of rats.
METHODS: Wistar rats (n=18) were randomly assigned to the control group or to receive 6 hours of PCV and PSV. After this
period, animals were euthanized and their diaphragms were excised, frozen in liquid nitrogen and stored in at -80º C for further
histomorphometric analysis.
RESULTS: Results showed a 15% decrease in cross-sectional area of muscle fibers on the PCV-C group when compared to the
control group (p<0.001) and by 10% when compared to the PSV group (p<0.05). Minor diameter was decreased in PCV-C group by
9% when compared with the control group (p<0.001) and by 6% when compared to the PSV group (p<0.05). When myonuclear area
was analyzed, a 16% decrease was observed in the PCV-C group when compared to the PSV group (p<0.05). No significant difference
between the groups was observed in myonuclear perimeter (p>0.05).
CONCLUSION: Short-term controlled mechanical ventilation seems to lead to muscular atrophy in diaphragm fibers. The PSV mode
may attenuate the effects of VIDD.
Key words: Anatomy & Histology. Diaphragm. Tracheostomy. Rats, Wistar.
RESUMO
OBJETIVO: Avaliar os efeitos do modo ventilatório controlado por pressão controlada (PCV-C) e do modo PSV sobre o músculo
diafragma de ratos.
MÉTODOS: Ratos (n = 18) da linhagem Wistar foram distribuídos no grupo controle (RE) ou para receber AVM por 6 horas no
modo PCV-C e no modo PSV. Após esse período, os animais foram eutanasiados, o diafragma retirado e encaminhado para a análise
histológica e morfométrica. RESULTADOS: Os resultados revelaram uma redução da área das fibras musculares de 15% no grupo
PCV-C em comparação ao controle (p<0,001) e de 10% quando comparado ao grupo PSV (p<0,05). Já com relação ao diâmetro menor
observou-se uma redução de 9% do grupo PCV-C em comparação ao controle (p<0,001) e de 6% em relação ao grupo PSV (p<0,05).
Quando avaliada a área dos mionúcleos, notou-se uma redução de 16% desse parâmetro no grupo PCV-C, comparado ao PSV (p<0,05).
Não houve diferença significativa no perímetro dos mionúcleos entre os grupos estudados (p>0,05).
CONCLUSÃO: O grupo PCV-C apresentou atrofia muscular em um período curto de ventilação mecânica. O modo PSV parece atenuar
os efeitos da DDIV.
Descritores: Anatomia & Histologia. Diafragma. Traqueostomia. Ratos Wistar.
Oliveira ASB et al.
110 - Acta Cirúrgica Brasileira - Vol. 27 (2) 2012
Introduction
Ventilator-induced diaphragmatic dysfunction (VIDD)
is characterized by a reduction in diaphragm force generation
capacity due to controlled mechanical ventilation (CMV) and was
recently shown to occur in humans
1
, being well-recognized in
animal models as well, like rats
2,3
, rabbits
4
, piglets
5
, and baboons
6
.
In rats, VIDD develops rapidly, as early as 12 hours after the
institution of CMV
7
.
This dysfunction has been implicated in weaning
failure
8,9
.
Although weaning failure may be due to numerous
factors, VIDD probably plays an important role.
Currently, underlying mechanisms responsible for such
phenomenon have not been fully elucidated. Studies demonstrated
the following alterations in the diaphragm after controlled
mechanical ventilation: reduced muscle mass
2,10,11
; diminished
type I, IIa, and IIx/b fiber dimensions
3,12,13
; myofibrillar damage
4
;
enhanced proteolysis
12
; increased protein oxidation and lipid
peroxidation
14
; reduced expression of the insulin-like growth
factor (IGF-I)
3
; decreased sarcoplasmic/endoplasmic reticulum
Ca
2+
-ATPase (SERCA-1a) expression
15
; increased expression of
muscle atrophy factor (MAF-box)
16
; and a decrease in myonuclear
content
17
. All of these factors seem to contribute to the development
of VIDD, but the precise contribution of each factor and their
apparition kinetics has yet to be defined.
Muscle atrophy and myonuclear loss are important
factors in the development of VIDD. The decreased volume of the
cytoplasm (atrophy) was observed in the presence of decreased
number of myonuclei, although the myonuclear domain (the
concept that each myonucleus controls the gene products in a
finite volume of a muscle fiber
17
) remained constant. This decrease
in myonuclear content was mediated by caspase-3-dependent
increased apoptosis, which was evident as early as 6 hours after
the onset of CMV
7
. Both the apoptosis and the atrophy were
attenuated by the inhibition of caspase-3
7
.
Although CMV can be too harmful to diaphragm
muscle fibers, few studies have been developed aiming VIDD
prevention
16,18,19
. Maybe diaphragmatic dysfunction could be
decreased by spontaneous breathing. Pressure support ventilation
has already proved to be efficient in patients with chronic
obstructive pulmonary disease and acute respiratory failure
20-22
. We
hypothesized that CMV would reduce morphometric parameters of
muscle fibers and myonuclei, and PSV, which preserves respiratory
muscle activity, would induce less diaphragmatic atrophy.
Methods
This study was performed in accordance with the
recommendations of Brazilian College of Animal Experimentation
(COBEA) and Animal Care Committee of Federal University of
Pernambuco (Protocol number 23076.012736/2008-16).
Eighteen Wistar rats (approximately 320g) were
individually housed and fed rat chow and water ad libitum and
were maintained on a 12-hour light-dark cycle for one week before
initiation of these experiments. Animals were assigned to 6 hours
of spontaneous breathing (SB) or mechanical ventilation on the
PCV-C or the PSV mode with 21% O
2
(Figure 1). All surgical
procedures were performed using aseptic techniques. After
reaching a surgical plane of anesthesia (sodium thiopental, 20
mg/kg of body weight, intraperitoneal) and sedation (diazepam,
5mg/kg body weight, intraperitoneal), animals were weighed
and tracheostomized. Body temperature was monitored (rectal
thermometer) and maintained at 37°C ±1°C with a recirculating
heating blanket. Continuing care during the experimental period
included expressing the bladder, eyes lubrification and passive
movements of the limbs. Airway pressure, tidal volume and flow
signals were monitored by the ventilator display. To prevent
atelectasis, lungs in the PCV-C and PSV groups were inflated in
a tidal volume of 15mL/kg for five consecutive breathings for 15
min during the 6 hours of experiment.
FIGURE 1 – Schematic illustration of the experimental design used. All
groups were assigned for 6 hours of SB or MV on PCV-C or PSV modes.
Protocol for controlled mechanical ventilation group
(PCV-C)
After surgical procedures, animals were mechanically
ventilated using a pressure-driven ventilator (Inter 5 Plus
Ventilator, Intermed, KESA, Pernambuco, Brazil) in PCV
(Pressure-Controlled Ventilation) mode for 6 hours. The tidal
Effects of controlled and pressure support mechanical ventilation on rat diaphragm muscle
Acta Cirúrgica Brasileira - Vol. 27 (2) 2012 - 111
volume was 10mL/kg body weight and the respiratory rate was
80 breaths per minute, with a fraction of inspired oxygen (FiO
2
)
of 21%, and positive end-expiratory pressure of 5 cmH
2
O. These
ventilator conditions resulted in complete diaphragmatic inactivity
and prevented noxious effects of hypercapnia on the muscular
contractile properties
4,10,12
. At the end of 6 hours, each animal was
weighed, and the right costal diaphragm was rapidly removed,
dissected and frozen in liquid nitrogen at -180º C. Samples were
stored at -80º C in a freezer until histological and morphometric
analysis.
Protocol for pressure support ventilation group (PSV)
After surgical procedures, animals were mechanically
ventilated using a pressure-driven ventilator (Inter 5 Plus
Ventilator, Intermed, KESA, Pernambuco, Brazil) in PSV mode for
6 hours. The level of pressure support applied, determined during
preliminary studies, allowed a minute volume of approximately
245 mL/minute (respiratory rate of approximately 70 breaths per
minute and FiO2 = 21%). The range of pressure support level used
was 5 – 8cmH
2
O. The ventilator had a flow trigger. The expiratory
trigger was 25% of peak inspiratory flow, and the maximum
inspiratory time was set at 1 second. The ventilator had a backup
ventilation, but it was not used during the experiments. If the
animal was not triggering, no pressure was released. Continuing
care during the experiment was also applied as above. At the end of
6 hours, each animal was weighed, and the right costal diaphragm
was rapidly removed, dissected and frozen in liquid nitrogen at
-180º C. Samples were stored at -80º C for further histological and
morphometric analysis.
Protocol for spontaneous breathing group (SB)
Control animals (SB) were free of mechanical ventilation
intervention. These animals were submitted to the drugs mentioned
above, tracheostomized, and were maintained with continuing
care as the other groups until the end of the experimental period
(6 hours). Then, their diaphragms were rapidly removed, dissected
and frozen in liquid nitrogen at -180º C. The samples were stored
at -80º C until subsequent assay.
Histological and histomorphometric analysis
After six hours of mechanical ventilation in the PCV-C
and the PSV group, and spontaneous breathing in the SB group,
all animals were sacrificed with large hemorrhage by abdominal
aortic and inferior vena cava section. Right costal diaphragm
was removed, dissected and weighed. Samples were fixed to
a cork holder with their fibers oriented perpendicularly to the
surface, rapidly frozen in liquid nitrogen and stored at -80º C.
Serial cross-sections parallel to the cork were done (10µm) with
cryostat (Leica, modelo CM 1100, Leica Microsystems Nussloch
GmbH, Germany) at -23º C and stained with hematoxylin and
eosin. Qualitative examination of these slides was performed by
an expert who was not aware of the experimental design of the
study. Quantitative examination was realized by computadorized
semiautomatic system and Image-lab 2000 software. The
parameters evaluated were area and minor diameter of the muscle
fibers and area and perimeter of the myonuclei.
Statistical analysis
Quantitative variables were expressed in mean ± standard
deviation. Kolmogorov-Smirnov test was applied to verify
normality. Differences between the PCV-C, PSV and SB groups
were tested by one-way analysis of variance (if normal), with post
hoc application (Tukey) of the least significant difference test. If
not normal, Mann-Whitney test was used. Statistical significance
was defined a priori as a P value of less than 0.05.
Results
General ndings
No significant difference between initial body weight
and final body weight in the studied groups was observed
(Table 1), indicating adequate hydration and nutrition during
experimental period. The doses of anesthetics and sedatives were
similar between groups. Only one death occurred in this study, in
the PCV-C group.
TABLE 1 - Body weight of PCV – C, PSV and SB
groups.
Values expressed in mean ± standard deviation
Definition of abbreviations: PCV – C = Pressure controlled ventilation
(controlled mechanical ventilation); PSV = Pressure Support Ventilation;
SB = Spontaneous Breathing
Histological analysis
Qualitative examination of the diaphragm sections stained
with hematoxylin and eosin did not reveal any abnormalities in
diaphragm histology (Figures 2 and 3). Some muscle fibers did
not show myonuclei. It happened because of section plane used.
PCV PSV SB
Initial body weight, g
312.33 ± 10.5 336.83 ± 8.4 335.33 ± 9.1
Final body weight, g
310.11 ± 11.8 335.45 ± 6.5 334.33 ± 7.7
Oliveira ASB et al.
112 - Acta Cirúrgica Brasileira - Vol. 27 (2) 2012
FIGURE 2 – Photomicrography of right diaphragm muscle of a rat in
PSV mode. We observe muscle fascicles. HE staining. 100X.
FIGURE 3 – Photomicrography of right diaphragm muscle of a rat in
PSV mode. We observe multinucleated cells with peripheral localization
(black arrows). The endomysium connective tissue is observed among
muscle fibers (open circle). HE staining. 400X.
Area and minor diameter of muscle bers
We found a significant decrease (p<0.001) of muscle
fibers area in the PCV-C group (407.70 µm
2
± 198.59 µm
2
) when
compared with the SB group (480.75 µm
2
± 246.54 µm
2
) and the
PSV group (453.43µm
2
± 215.97 µm
2
), with p=0.003 (Figure 4).
FIGURE 4 – Effects of controlled mechanical ventilation (PCV-C) and
Pressure Support Ventilation (PSV) on rat diaphragm muscle fibers area.
We observe muscle atrophy in the PCV-C group when compared to the
control group (SB) and to the PSV group. Values are represented as mean
± standard deviation. a (p<0.001) indicates difference between the PCV-C
and the SB groups; b (p<0.05) indicates difference between the PCV-C
and the PSV groups (Mann-Whitney test).
When we analyzed minor diameter of muscle fibers, we
found similar results: the PCV-C group (18.70µm ± 5.13µm) had a
significant reduction (p<0.001) in minor diameter when compared
to the SB group (20.43µm ± 5.49µm), and to the PSV group
(19.89µm ± 5.32µm), with p=0.002 (Figure 5).
FIGURE 5 - Effects of controlled mechanical ventilation (PCV-C) and
Pressure Support Ventilation (PSV) in rat diaphragm muscle fibers minor
diameter. We observe muscle atrophy in the PCV-C group when compared
to the control group (SB) and to the PSV group. Values are represented
as mean ± standard deviation. a (p<0.001) indicates difference between
PCV-C and SB groups; b (p<0.05) indicates difference between PCV-C
and PSV groups (Mann-Whitney test).
Area and perimeter of myonucleus
The PCV-C group (2.30µm
2
± 0.80µm
2
) showed a
reduction in myonuclei area when compared with the SB group
(2.44µm
2
± 1.05µm
2
), but the difference was not significant
(p=0,618). The PSV group revealed an increase in myonuclei
area (2.73µm
2
± 0.989µm
2
) when compared to the control group
(SB), but this difference was not significant (p=0.056). Significant
Effects of controlled and pressure support mechanical ventilation on rat diaphragm muscle
Acta Cirúrgica Brasileira - Vol. 27 (2) 2012 - 113
reduction (p=0.002) was observed in myonuclei area of the PCV-C
group when compared with the PSV group (Figure 6).
FIGURE 6 - Effects of controlled mechanical ventilation (PCV-C) and
Pressure Support Ventilation (PSV) in myonuclei area of rat diaphragm
muscle fibers. We observe muscle atrophy in PCV-C group compared
to PSV group. Values are represented as mean ± standard deviation. a
(p<0.05) (ANOVA, followed by Tukey test).
When myonuclei perimeter was analyzed, significant
differences between the groups were not observed: PCV-C (7.31m
± 1.47µm), PSV (7.49µm ± 1.46µm) and RE (7.31µm ± 1.68µm),
with p value of 0.065 (Figure 7).
FIGURE 7 - Effects of controlled mechanical ventilation (PCV-C)
and Pressure Support Ventilation (PSV) in myonuclei perimeter of rat
diaphragm muscle fibers. No differences were observed between groups
(p>0.05). Values are represented as mean ± standard deviation. (ANOVA,
followed by Tukey test).
Discussion
The major finding of this study, which is the second
to compare the PSV mode with the CMV mode, is that, unlike
the CMV, the PSV mode seems to attenuate diaphragmatic
muscle disuse atrophy due to ventilatory support. This ventilator-
induced diaphragmatic dysfunction (VIDD), analyzed in many
studies, may be due to: muscle disuse atrophy, reduced protein
synthesis, increased proteolytic activity, oxidative stress, intrinsic
abnormalities (ultrastructural level) of muscle fibers, problems
with the excitation-contraction coupling and myonuclear
loss
2,7,8,12,16,23,24
.
Analysis of experimental design
Animal model was chosen to investigate the effects of
mechanical ventilation (MV) because of the invasive nature of
obtaining diaphragmatic biopsy in humans. Our considerations to
choosing animal models involve pragmatic factors (animal size
and cost) and the extrapolation of animal models to humans. In
relation to pragmatic factors, rat is a relatively cheap model to study
the effects of MV, and does not impose any technical difficulties
during tracheostomy. Regarding the applicability in humans, rat is
an excellent model to investigate diaphragm muscle, because both
human and rat diaphragms are similar in anatomy, muscle fiber
types and function
25,26
.
To investigate the effects of MV on diaphragm, controlled
mechanical ventilation (CMV) was chosen for two reasons. First,
this mode has the advantage of producing rapid muscle atrophy
12
.
Second, although many patients receive assisted MV, i.e., with
diaphragmatic participation, CMV has clinical relevance because
this mode is used in adult patients on many circumstances (for
ex: drugs overdose, spinal cord injuries, surgeries, etc). It is also
well-recognized in some pediatric situations
27
. Pressure support
ventilation (PSV) was chosen because literature has only one study
investigating the attenuation of protein catabolic effects by using
this ventilation mode
28
. This study analyzes diaphragmatic muscle
atrophy and the PSV mode seems to preserve diaphragmatic
muscle activity when compared with the CMV mode.
In this investigation, all groups received similar doses
of anesthetics and sedatives during the experimental period.
Animals did not receive anesthetic doses in a continuous form or
neuromuscular blockers, like in other studies
6,10
. Barbiturates and
neuromuscular blockers have deleterious effects in skeletal muscle
function
29
. When applied on an intermittent manner, nevertheless,
they do not contribute to VIDD
28
.
During the experimental period of the PCV-C
group, diaphragmatic electromyography was not used in our
investigation, as seen in other studies about VIDD
4
. The objective
of passive ventilation maybe could not be achieved, and it is
possible that animal-ventilator asynchrony could have caused
eccentric contractions, resulting in muscle lesion. The animals in
our study, however, were monitored by flow and airway pressure
waves. Alterations in airway pressure and flow waves suggest
Oliveira ASB et al.
114 - Acta Cirúrgica Brasileira - Vol. 27 (2) 2012
inspiratory efforts during MV, and have been show to coincide
with electromyographic analysis
30
. Uniform airway pressure and
flow waves analyzed by the ventilator display, together with the
consistence of the respiratory frequency set by the investigator,
indicate that passive ventilation was in fact achieved. Occasionally,
moments of diaphragmatic activity were observed, but were
suppressed by adjusts in peak pressure, to increase tidal volume
and consequently depress the respiratory center.
In the present study sodium bicarbonate was not
administered to prevent metabolic acidosis. Metabolic acidosis
can potentially influence diaphragmatic contractility
31,32
. However,
a study demonstrated no decrease in diaphragm strength when
pH>6,8
33
. In this study, before each animal sacrifice, their arterial
blood gas was analyzed, and all animals showed pH>7.1.
Muscle atrophy
During MV, the diaphragm is intermittently and
repetitively shortened by cyclical lung inflation
34
. Therefore,
changes in the respiratory rate and tidal volume applied during
mechanical ventilation will necessarily alter the speed and extent
of diaphragmatic shortening. The use of PEEP, on the other
hand, will lead to baseline diaphragm shortening at functional
residual capacity. It has long been known that the adverse effects
of disuse on limb muscle structure are exacerbated by muscle
shortening
35
. In addition, maintaining skeletal muscles (including
the diaphragm) in a shortened position causes a loss of sarcomeres
in series
36,37
. Interestingly, two studies that employed PEEP found
that CMV for 48 hours or more resulted in significantly decreased
diaphragm muscle optimal length, a finding that strongly suggests
the occurrence of such sarcomere loss
10,11
. We applied a PEEP of
5cmH2O in our study because, in pilot study, rats experimented
ventilator asynchrony and suffered acute lung edema when values
below that were used. Differences in myosin isoform expression
patterns and the degree of atrophy observed among certain studies
(in our study as well) may also be at least partly related to the levels
of diaphragmatic shortening imposed by the specific ventilator
settings applied in these investigations, especially by PEEP.
Controlled mechanical ventilation induces diaphragm
muscle atrophy
10-13
. VIDD develops rapidly, as early as 12 h after
the institution of CMV
17
, and is more pronounced in the diaphragm,
which atrophies earlier than the peripheral skeletal muscles that
are also inactive during CMV
10-12
. CMV, in our study, resulted
in diaphragm muscle atrophy in only 6 hours of MV, which is a
period shorter than seen on other studies.
Although reductions in force-generating capacity
found after CMV cannot be attributed only to muscle atrophy,
diaphragmatic loss alters maximum force generation in vivo.
In addition, the susceptibility of diaphragmatic fatigue in vivo
is inversely proportional to maximum force
38
, indicating that
diaphragmatic atrophy will increase the risk of diaphragmatic
fatigue once spontaneous breathing is assumed again (for instance,
with two mechanical ventilation weaning trials
39
). Reduction in
diaphragm muscle mass and/or atrophy of muscle fibers after
CMV were observed in our study. In general, disuse atrophy can be
a result of decreased protein synthesis
40
, increased proteolysis
41
, or
both. Only in 6 hours of CMV, rats underwent an in vivo reduction
in the protein synthesis rate of all muscle proteins by 30% and in
the myosin heavy chain protein rate by 65%, both persisting during
18 hours of CMV
42
. In addition, 24 hours of CMV suppressed the
levels of IGF-1 (insulin-growth factor) mRNA, which stimulates
protein synthesis
3
. CMV, therefore, decreases protein synthesis in
diaphragm muscle.
An increase in proteolysis in animals diaphragm
submitted to 18 hours of CMV has already been studied
12
. All
mammalian cells proteases systems (lysossomal proteases,
calpains, caspases and proteasome system
43
) are activated after the
onset of CMV
7,12,44
, which is one more cause of the muscle fibers
atrophy in PCV-C group observed in our study.
The decrease in area and minor diameter of muscle
fibers observed in this study in the PCV-C group were not
accompanied by reduction in area and perimeter of myonuclei
when compared with the control group (SB). Skeletal muscle
cells are multinucleated and, theoretically, a single myonucleus
can supply the necessary gene expression for a determined area of
cytoplasm, a relationship called myonuclear domain
17
. Literature
demonstrates a decreased volume of the cytoplasm (atrophy),
which is accompanied by a decreased number of myonuclei,
not analyzed in our study, but resulting in constant myonuclear
domain
7
.That decrease in myonuclear content is mediated by an
increase in caspase-3-dependent apoptosis, which was evident
after only 6 hours of CMV
7
. Both apoptosis and atrophy were
attenuated with caspase-3 inhibition. It is yet uncertain if assisted
modes of mechanical ventilation, like the PSV mode, used in
our study, could attenuate these deleterious effects of ventilatory
support (muscle fiber atrophy and decreased myonuclei number).
Our study demonstrated that the PSV mode attenuated
muscle fiber atrophy of diaphragm in rats. Moreover, in contrast
with the PCV-C group, the PSV mode did not show a decrease in
area and perimeter of myonuclei when compared to control (SB).
Interestingly, the PSV group demonstrated an increase in area and
perimeter of myonuclei when compared to the SB group, although
this difference was not significant. Also, significant difference was
Effects of controlled and pressure support mechanical ventilation on rat diaphragm muscle
Acta Cirúrgica Brasileira - Vol. 27 (2) 2012 - 115
observed in myonuclear area in the PCV-C group when compared
with the PSV group. These differences in muscle fiber atrophy can
be due to differences in the type of muscle lesion caused by the
CMV and the PSV modes. In fact, like peripheral skeletal muscle
models, during PSV, diaphragm undergoes a type of exercise in
which there is an increase in respiratory activity (in comparison
to the CMV)
45-47
. This exercise could protect diaphragm from
modifications related to muscular inactivity caused by CMV.
During CMV, there is a complete absence of neural activation and
diaphragm mechanical activity
2,4
, and a passive shortening of this
muscle during lungs inflation
34,36
. This trauma has been implicated
in the origin of VIDD
12,42
, particularly during sarcomere injury
36,37
and during decreased force-generating capacity of diaphragm
8,11
.
Conclusions
The pressure support ventilation, in a few hours (six),
seems to be capable of attenuating the deleterious effects observed
when controlled mechanical ventilation is used, related to muscle
fiber atrophy. We collected left diaphragm for further biochemical
studies to correlate with the findings of this study and maybe
suggest, with better scientific support, that the PSV mode can be
an alternative way of limiting muscle atrophy and diaphragmatic
dysfunction.
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Aknowledgements
The authors thank Antonio Roberto, chief of Experimental
Surgery Department of Federal University of Pernambuco (UFPE)
and his employees, for their assistance and Edeones França, for
his technical and scientific support. This work was supported by
CNPq and PROPESQ/UFPE
Correspondence:
André de Sá Braga Oliveira
Programa de Pós-Graduação em Patologia (UFPE)
Cidade Universitária, s/n
50670-901 Recife – PE Brasil
Tel.: (55 81)2126-8515
Fax: (55 81)2126-8529
andre.sboliveira@gmail.com
Received: September 21, 2011
Review: November 23, 2011
Accepted: December 20, 2011
Conflict of interest: none
Financial sources: CNPq and PROPESQ/UFPE
¹Research performed at Laboratory of Experimental Surgery,
Federal University of Pernambuco (UFPE), Brazil.
