In the United States, about 500,000 sudden cardiac deaths are registered each year. Global brain ischemia is the major pathophysiological event that limits the time available for patient rescue to 5-10 min. This study investigates the effects of antioxidative therapy on metabolic and functional changes in the brain during and after cardiac arrest. A model of asphyxial cardiac arrest in rats developed by the applicant and his sponsor will be used. Modern NMR methods will be applied for noninvasive in vivo evaluation of parameters of energy metabolism, cerebral blood flow, and ion/water disbalance. Interleaved 31P/1H NMR spectroscopy will be used to estimate ATP, phosphocreatine, inorganic phosphate, lactate, N-acetyl-L-aspartate content, and intracellular pH in the brain. Swelling pattern and distribution and intensity of cerebral blood flow will be measured by precise ADC and perfusion mapping of the brain based on contemporal newly-developed imaging techniques. Animals' survival, histological and neurological outcomes will also be evaluated. The optimal combination of inhibitors of lipid peroxidation with various mechanisms of action for effective treatment of global ischemia during cardiac arrest will be determined as a result of proposed study.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32HL009784-01A2
Application #
2771212
Study Section
Special Emphasis Panel (ZRG7-SSS-8 (48))
Project Start
1999-07-14
Project End
Budget Start
1999-02-01
Budget End
2000-01-31
Support Year
1
Fiscal Year
1999
Total Cost
Indirect Cost
Name
University of Pittsburgh
Department
Anesthesiology
Type
Schools of Medicine
DUNS #
053785812
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Liachenko, Serguei; Tang, Pei; Xu, Yan (2003) Deferoxamine improves early postresuscitation reperfusion after prolonged cardiac arrest in rats. J Cereb Blood Flow Metab 23:574-81
Xu, Yan; Liachenko, Serguei; Tang, Pei (2002) Dependence of early cerebral reperfusion and long-term outcome on resuscitation efficiency after cardiac arrest in rats. Stroke 33:837-43
Liachenko, S; Tang, P; Hamilton, R L et al. (2001) Regional dependence of cerebral reperfusion after circulatory arrest in rats. J Cereb Blood Flow Metab 21:1320-9