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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
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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 standard1 treatment for end-stage heart failure • ISHLT: 85,0002 cardiac transplantations until 2009 • Limitation: scarcity of donors3 1.J Card Surg. 2007;22(4):287-94. 2.J Heart Lung Transplant. 2009;28(10):1007-22. 3.Acta Anaesthesiol Scand. 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.
Methods Male Wistar rats 250-350g BD by rapid intracranial hypertension Thoracic epidural anesthesia (bupivacaine 0.5%) Durantion of observation: 6h after BD
Experimental Design Group 1 / Group 2 20 L saline or bupivacaine Group 3 20 L bupivacaine Group 4 20 L bupivacaine -2 0 20 60 180 360 min Surgical procedure and 10 min stabilization Blood gases, leucometry, hematocrit Brain Death continuous monitoring of mean arterial pressure Euthanasia and tissue collecting
Results • Mean Arterial Pressure Control Pre-bupi Bupi-20 Bupi-60 MAP (mmHg) Brain Death Time (min)
Results • Leukocytes White Blood Cell Counts Control Pre – bupi Bupi – 20 Bupi – 60 p = 0,875 Pre 3 h 6 h
Results • Cytokine levels TNF- IL-1 p= 0.58 p= 0.55 Serum Control PreBup Bup20 Bup60 Control PreBup Bup20 Bup60 TNF- IL-1 p= 0.94 p= 0.39 Tissue Control Prebup Bup20Bup60 Control Pre-Bup Bup20 Bup60
Results • Expression of Adhesion Molecules VCAM ICAM-1 Mean Intensity of Fluorescence Mean Intensity of Fluorescence Control Bup-Pre Bup20 Bup60 Control Bup-Pre Bup20 Bup60
Results • Immunohistochemistry Caspase-3 Bcl-2 -Actin Control BupPre Bup20 Bup60 Control BupPre Bup20 Bup60 Control BupPre Bup20 Bup60
Conclusions • TEA effectively blocked the hemodynamic storm • Animals evolved with Leukopenia • TEA did not change inflammatory response • TEA did not change apoptosis
Perspectives Autonomic storm may not be responsible for myocardial derrangements in BD scenario.
Thank you! isaacazevedo@yahoo.com