Brain death, autonomic storm and inflammatory response. An experimental study in rats.

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Brain death, autonomic Brain death, autonomic storm and inflammatory storm and inflammatory response. An response. An experimental study in experimental study in rats. rats. Authors: Authors: Silva, IA Silva, IA ; Simas, R; Correia, CJ; ; Simas, R; Correia, CJ; Cruz, JWMC; Zanoni, FL; Ferreira, SG; Cruz, JWMC; Zanoni, FL; Ferreira, SG; Menegat, L; Judas, GI; Sannomyia, P; Moreira, Menegat, L; Judas, GI; Sannomyia, P; Moreira, LFP. LFP. Heart Institute – University of Heart Institute – University of Sao Paulo Medical School Sao Paulo Medical School Sao Paulo - Brazil Sao Paulo - Brazil

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Brain death, autonomic storm and inflammatory response. An experimental study in rats. Authors: Silva, IA ; Simas, R; Correia, CJ; Cruz, JWMC; Zanoni, FL; Ferreira, SG; Menegat, L; Judas, GI; Sannomyia, P; Moreira, LFP. Heart Institute – University of Sao Paulo Medical School - PowerPoint PPT Presentation

Transcript of Brain death, autonomic storm and inflammatory response. An experimental study in rats.

Page 1: 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

Page 2: Brain death, autonomic storm and inflammatory response. An experimental study in rats.

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.

Page 3: Brain death, autonomic storm and inflammatory response. An experimental study in rats.

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.

Page 4: Brain death, autonomic storm and inflammatory response. An experimental study in rats.

Aim

Investigate the hypothesis that thoracic epidural anesthesia (TEA) could block the autonomic storm and then improve the condition of

graft.

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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

Page 6: Brain death, autonomic storm and inflammatory response. An experimental study in rats.

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

Page 7: Brain death, autonomic storm and inflammatory response. An experimental study in rats.

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

Page 8: Brain death, autonomic storm and inflammatory response. An experimental study in rats.

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

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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

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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

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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

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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

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Perspectives

Autonomic storm may not be responsible for myocardial

derrangements in BD scenario.

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Thank you!Thank you! [email protected]@yahoo.com