Brain death, autonomic storm and inflammatory response. An experimental study in rats.
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Transcript of Brain death, autonomic storm and inflammatory response. An experimental study in rats.
Brain death, autonomic Brain death, autonomic storm and storm and
inflammatory response. inflammatory response. An experimental study An experimental study
in rats. in rats.
Authors: Authors: Silva, IASilva, IA; Simas, R; Correia, CJ; Cruz, JWMC; ; Simas, R; Correia, CJ; Cruz, JWMC; Zanoni, FL; Ferreira, SG; Menegat, L; Judas, GI; Zanoni, FL; Ferreira, SG; Menegat, L; Judas, GI;
Sannomyia, P; Moreira, LFP.Sannomyia, P; Moreira, LFP.
Heart Institute – University of Sao Paulo Heart Institute – University of Sao Paulo Medical SchoolMedical School
Sao Paulo - BrazilSao Paulo - Brazil
IntroductionIntroduction
Cardiac transplantation: gold Cardiac transplantation: gold standardstandard11 treatment for end-stage treatment for end-stage heart failureheart failure
ISHLT: 85,000ISHLT: 85,00022 cardiac cardiac transplantations until 2009transplantations until 2009
Limitation: scarcity of donorsLimitation: scarcity of donors33
1.1.J Card J Card SurgSurg.. 2007;22(4):287-94. 2007;22(4):287-94.
2.2.J Heart Lung Transplant. 2009;28(10):1007-22. 2009;28(10):1007-22.
3.3.Acta Anaesthesiol Scand. 2009;53(4):425-35. 2009;53(4):425-35.
BD and cardiac dysfunction
Myocardial dysfunction is comon after BD
In 20 to 25% it precludes the use of these hearts1,2
The mechanisms remain unclear There are many questions about
the autonomic storm3 in BD cardiac dyfunction
1.Transplantation. 2000;70(10):1498-506.2.Circulation. 2001;104(12 Suppl 1):I192-6.
3.J Card Surg. 2010;25(1):98-106.
Aim
Investigate the hypothesis that thoracic epidural anesthesia (TEA) could block the autonomic storm and then improve the condition of
graft.
MethodsMethods
Male Wistar rats 250-350gMale Wistar rats 250-350g BD by rapid intracranial BD by rapid intracranial
hypertensionhypertension Thoracic epidural anesthesia Thoracic epidural anesthesia
(bupivacaine 0.5%)(bupivacaine 0.5%) Durantion of observation: 6h after Durantion of observation: 6h after
BDBD
Experimental DesignExperimental Design
Group 1 / Group 220 L saline or
bupivacaine
Brain Death
Surgical procedure and
10 min stabilization
Group 320 L
bupivacaine
Group 4 20 L
bupivacaine
continuous monitoring of mean arterial pressure
Blood gases, leucometry, hematocrit
Euthanasia and tissue collecting
-2 0 20 60 180 360 min
ResultsResults
Mean Arterial PressureMean Arterial Pressure
0
20
40
60
80
100
120
140
160
180
200
Tempo (min)
PAM
(mm
Hg)
Controle
Bupi - pré morte
Bupi - 20 min.
Bupi - 60 min.
Control
Pre-bupi
Bupi-20
Bupi-60
Time (min)Bra
in
Death
ResultsResults
LeukocytesLeukocytesLeucócitos Séricos
Pré 3 Horas 6 Horas0
5000
10000
15000ControleBupi - PréBupi - 20Bupi - 60
Grupo - p = 0,875Interação - p= 0,507
White Blood Cell Counts
ControlPre – bupiBupi – 20Bupi – 60
p = 0,875
Pre 3 h 6 h
ResultsResults
Cytokine levelsCytokine levelsTNF
pg
/mL
0
200
400
600
p = 0,55
Interleucina 1 Beta
pg
/mL
0
200
400
600
p = 0,58
TNF
pg
/g
0
50
100
150p = 0,94
Interleucina 1 Beta
0
2000
4000
6000
8000
10000
p = 0,385p
g/g
Control PreBup Bup20 Bup60
Control PreBup Bup20 Bup60
Control Pre-Bup Bup20 Bup60
Control Prebup Bup20Bup60
TNF- IL-1
TNF- IL-1p= 0.39p= 0.94
p= 0.58p= 0.55
ResultsResults
Expression of Adhesion MoleculesExpression of Adhesion MoleculesExpressão de VCAM
Inte
nsi
dad
e m
édia
de
fluo
resc
ênci
a
0
50
100
150
200
p = 0,863
Expressão de ICAM-1
Inte
nsi
dad
e m
édia
de
fluo
resc
ênci
a
0
5000
10000
15000
20000
25000
p = 0,83
VCAM ICAM-1
Control Bup-Pre Bup20 Bup60
Control Bup-Pre Bup20 Bup60
ResultsResults
ImmunohistochemistryImmunohistochemistry
Caspase-3
0.00
0.05
0.10
0.15
0.20
0.25p=0,427
Bcl-2
0.00
0.02
0.04
0.06p=0,864
Alfa-Actina
0
20
40
60
80
100p=0,657
Caspase-3 Bcl-2 -Actin
Control BupPre Bup20 Bup60
Control BupPre Bup20 Bup60
Control BupPre Bup20 Bup60
ConclusionsConclusions
TEA effectively blocked the TEA effectively blocked the hemodynamic storm hemodynamic storm
Animals evolved with LeukopeniaAnimals evolved with Leukopenia TEA did not change inflammatory TEA did not change inflammatory
responseresponse TEA did not change apoptosis TEA did not change apoptosis
Perspectives
Autonomic storm may not be responsible for myocardial
derrangements in BD scenario.
Thank you!Thank you! [email protected]@yahoo.com