Brain death, autonomic storm and inflammatory response. An experimental study in rats. Authors: Silva, IA; Simas, R; Correia, CJ; Cruz, JWMC; Zanoni, FL;

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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 Sao Paulo - Brazil

Introduction Cardiac transplantation: gold standard 1 treatment for end-stage heart failure Cardiac transplantation: gold standard 1 treatment for end-stage heart failure ISHLT: 85,000 2 cardiac transplantations until 2009 ISHLT: 85,000 2 cardiac transplantations until 2009 Limitation: scarcity of donors 3 Limitation: scarcity of donors ;22(4): J Card Surg. 2007;22(4): J Card Surg. 2.J Heart Lung Transplant. 2009;28(10): J Heart Lung Transplant.J Heart Lung Transplant. 3.Acta Anaesthesiol Scand. 2009;53(4): Acta Anaesthesiol Scand.Acta Anaesthesiol Scand.

BD and cardiac dysfunction Myocardial dysfunction is comon after BD In 20 to 25% it precludes the use of these hearts 1,2 The mechanisms remain unclear There are many questions about the autonomic storm 3 in BD cardiac dyfunction 1.Transplantation. 2000;70(10): Transplantation. 2.Circulation. 2001;104(12 Suppl 1):I192-6.Circulation. 3.J Card Surg. 2010;25(1): J Card Surg.

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

Methods Male Wistar rats g Male Wistar rats g BD by rapid intracranial hypertension BD by rapid intracranial hypertension Thoracic epidural anesthesia (bupivacaine 0.5%) Thoracic epidural anesthesia (bupivacaine 0.5%) Durantion of observation: 6h after BD Durantion of observation: 6h after BD

Experimental Design Group 1 / Group 2 20  L saline or bupivacaine Brain Death Surgical procedure and 10 min stabilization Group 3 20  L bupivacaine Group 4 20  L bupivacaine continuous monitoring of mean arterial pressure Blood gases, leucometry, hematocrit Euthanasia and tissue collecting min

Results Mean Arterial Pressure Mean Arterial Pressure Control Pre-bupi Bupi-20 Bupi-60 MAP (mmHg) Time (min) Brain Death

Results Leukocytes Leukocytes White Blood Cell Counts Control Pre – bupi Bupi – 20 Bupi – 60 p = 0,875 Pre3 h6 h

Results Cytokine levels Cytokine levels Control PreBup Bup20 Bup60 Control Pre-Bup Bup20 Bup60 Control Prebup Bup20Bup60 TNF-  IL-1  TNF-  IL-1  p= 0.39p= 0.94 p= 0.58 p= 0.55 Serum Tissue

Results Expression of Adhesion Molecules Expression of Adhesion Molecules VCAMICAM-1 Control Bup-Pre Bup20 Bup60 Mean Intensity of Fluorescence

Results Immunohistochemistry Immunohistochemistry Caspase-3Bcl-2  -Actin Control BupPre Bup20 Bup60

Conclusions TEA effectively blocked the hemodynamic storm TEA effectively blocked the hemodynamic storm Animals evolved with Leukopenia Animals evolved with Leukopenia TEA did not change inflammatory response TEA did not change inflammatory response 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!