This proposal is for ongoing study of ways to improve cerebral protection during operations on the heart and great vessels which require arrest of antegrade circulation. Clinical and experimental data suggest that subtle cerebral injury occurs if the duration of hypothermic circulatory arrest (HCA) is more than 30 minutes even under optimal circumstances, and some complex procedures cannot reliably be completed in so short a time. In our porcine experimental model, the effect of strategies such as retrograde cerebral perfusion (RCP) can be studied to see whether they can be used to extend the safe duration of HCA to 60 minutes. In this clinically relevant model, the effect of changes in the implementation of HCA and RCP on cerebral blood flow, cerebral metabolism, intracranial pressure, electrophysiological recovery, behavioral outcome (including preservation of ability to learn conditioned reflexes) and cerebral histopathology can be used to see whether new approaches, such as use of lower temperatures, postoperative ultrafiltration, cold reperfusion, and treatment with various pharmacological agents are likely to improve neurological outcome after operations requiring HCA. The hypothesis that some of the cerebral injury following HCA/RCP is occurring as a consequence of apoptosis, or programmed cell death, opens up the possibility of arresting this suicidal cascade using specific inhibitors of the proteases and endonucleases which participate in this process as well as inhibitors of protein synthesis, all of which have had dramatic success in reducing injury in rodent models of cerebral ischemia. The results of this study will make a significant contribution toward improving long-term outcome of complex surgery on the heart and great vessels in both infants and adults.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL045636-10
Application #
6389155
Study Section
Surgery and Bioengineering Study Section (SB)
Program Officer
Ershow, Abby
Project Start
1991-09-01
Project End
2004-07-31
Budget Start
2001-08-01
Budget End
2002-07-31
Support Year
10
Fiscal Year
2001
Total Cost
$540,485
Indirect Cost
Name
Mount Sinai School of Medicine
Department
Surgery
Type
Schools of Medicine
DUNS #
114400633
City
New York
State
NY
Country
United States
Zip Code
10029
Geisbüsch, Sarah; Stefanovic, Angelina; Koruth, Jacob S et al. (2014) Endovascular coil embolization of segmental arteries prevents paraplegia after subsequent thoracoabdominal aneurysm repair: an experimental model. J Thorac Cardiovasc Surg 147:220-6
Scheumann, Johannes; Heilmann, Claudia; Beyersdorf, Friedhelm et al. (2012) Early histological changes in the porcine aortic media after thoracic stent-graft implantation. J Endovasc Ther 19:363-9
Geisbüsch, Sarah; Schray, Deborah; Bischoff, Moritz S et al. (2012) Imaging of vascular remodeling after simulated thoracoabdominal aneurysm repair. J Thorac Cardiovasc Surg 144:1471-8
Bischoff, Moritz S; Scheumann, Johannes; Brenner, Robert M et al. (2011) Staged approach prevents spinal cord injury in hybrid surgical-endovascular thoracoabdominal aortic aneurysm repair: an experimental model. Ann Thorac Surg 92:138-46; discussion 146
Etz, Christian D; Kari, Fabian A; Mueller, Christoph S et al. (2011) The collateral network concept: a reassessment of the anatomy of spinal cord perfusion. J Thorac Cardiovasc Surg 141:1020-8
Bischoff, Moritz S; Di Luozzo, Gabriele; Griepp, Eva B et al. (2011) Spinal cord preservation in thoracoabdominal aneurysm repair. Perspect Vasc Surg Endovasc Ther 23:214-22
Etz, Christian D; Kari, Fabian A; Mueller, Christoph S et al. (2011) The collateral network concept: remodeling of the arterial collateral network after experimental segmental artery sacrifice. J Thorac Cardiovasc Surg 141:1029-36
Etz, Christian D; Zoli, Stefano; Bischoff, Moritz S et al. (2010) Measuring the collateral network pressure to minimize paraplegia risk in thoracoabdominal aneurysm resection. J Thorac Cardiovasc Surg 140:S125-30; discussion S142-S146
Etz, Christian D; Luehr, Maximilian; Kari, Fabian A et al. (2008) Paraplegia after extensive thoracic and thoracoabdominal aortic aneurysm repair: does critical spinal cord ischemia occur postoperatively? J Thorac Cardiovasc Surg 135:324-30
Etz, Christian D; Homann, Tobias M; Luehr, Maximilian et al. (2008) Spinal cord blood flow and ischemic injury after experimental sacrifice of thoracic and abdominal segmental arteries. Eur J Cardiothorac Surg 33:1030-8

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