Abstract

The applicants have shown that Electron Spin Resonance (ESR) spectroscopy can directly detect free radical generation in isolated perfused rat and rabbit hearts. However, it is unknown whether free radicals are generated during cardiac operations. They hypothesize that free radicals are manifest intraoperatively in myocardial tissue during the cycle of ischemia and reperfusion. They plan to investigate clinically relevant aspects of the free radical hypotheses relating to the myocardial injury in isolated, perfused rat and rabbit hearts subjected to conditions of surgical ischemia and reperfusion. They will attempt to directly detect and rigorously characterize free radicals produced in the cardiac surgical model by the combined use of ESR trapping and Mass Spectrometry. They will also explore and advance the possibility of in vivo ESR measurements of free radicals in intact, isolated hearts subjected to normothermic and hypothermic ischemia. They will determine (Specific Aim 1) whether surgical ischemia and reperfusion results in the generation of toxic radical species. They will then determine (Specific Aim 2) possible mechanisms of radical generation during surgical ischemia and reperfusion, and then assess (Specific Aim 3) the extent to which free radical generating processes are operative during clinically relevant conditions of hypothermic ischemia in comparison to normothermic ischemia. Finally, they will assess (Specific Aims 4 and 5) the feasibility of directly measuring free radicals and the concentration of molecular oxygen in intact hearts subjected to normothermic and hypothermic ischemia.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL045048-03
Application #
3363929
Study Section
Surgery, Anesthesiology and Trauma Study Section (SAT)
Project Start
1990-07-01
Project End
1993-11-30
Budget Start
1992-07-01
Budget End
1993-11-30
Support Year
3
Fiscal Year
1992
Total Cost
Indirect Cost

  Institution

Name
Medical College of Wisconsin
Department
Type
Schools of Medicine
DUNS #
073134603
City
Milwaukee
State
WI
Country
United States
Zip Code
53226

  Publications

Eells, J T; Henry, M M; Gross, G J et al. (2000) Increased mitochondrial K(ATP) channel activity during chronic myocardial hypoxia: is cardioprotection mediated by improved bioenergetics? Circ Res 87:915-21
Baker, J E; Holman, P; Kalyanaraman, B et al. (1998) Adaptation of hearts to chronic hypoxia increases tolerance to subsequent ischemia by increased nitric oxide production. Adv Exp Med Biol 454:203-17
Ferguson, E; Parthasarathy, S; Joseph, J et al. (1998) Generation and initial characterization of a novel polyclonal antibody directed against homocysteine thiolactone-modified low density lipoprotein. J Lipid Res 39:925-33
Baker, J E; Froncisz, W; Joseph, J et al. (1997) Spin label oximetry to assess extracellular oxygen during myocardial ischemia. Free Radic Biol Med 22:109-15
Ferguson, E; Singh, R J; Hogg, N et al. (1997) The mechanism of apolipoprotein B-100 thiol depletion during oxidative modification of low-density lipoprotein. Arch Biochem Biophys 341:287-94
Baker, J E; Curry, B D; Olinger, G N et al. (1997) Increased tolerance of the chronically hypoxic immature heart to ischemia. Contribution of the KATP channel. Circulation 95:1278-85
Baker, J E; Contney, S J; Gross, G J et al. (1997) KATP channel activation in a rabbit model of chronic myocardial hypoxia. J Mol Cell Cardiol 29:845-8
Hogg, N; Singh, R J; Kalyanaraman, B (1996) The role of glutathione in the transport and catabolism of nitric oxide. FEBS Lett 382:223-8
Kalyanaraman, B (1996) Detection of nitric oxide by electron spin resonance in chemical, photochemical, cellular, physiological, and pathophysiological systems. Methods Enzymol 268:168-87
Konorev, E A; Joseph, J; Kalyanaraman, B (1996) S-nitrosoglutathione induces formation of nitrosylmyoglobin in isolated hearts during cardioplegic ischemia--an electron spin resonance study. FEBS Lett 378:111-4

Showing the most recent 10 out of 21 publications