This application is concerned with mechanisms of defibrillation injury. Our overall aim is to demonstrate, using new real-time electron paramagnetic spin resonance techniques, that a major mechanism of defibrillation injury is oxygen free radicals which are generated by electric countershocks. We want to reduce defibrillation injury by pharmacologic interventions with free radical scavengers or inhibitors to reduce defibrillation injury. To accomplish these aims we propose a testable hypothesis: A major mechanism of defibrillation injury (which results in post shock ventricular dyskinesis) is generation of oxygen free radicals, due to a direct shock effect (passage of electrical current through physiologic solutions) rather than to the myocardial ischemia which accompanies ventricular fibrillation. Defibrillation injury can be reduced by pharmacologic interventions which reduce or scavenge free radicals. New defibrillation waveforms may reduce free radical generation. We will use a marker for the detection and quantification of free radical generation: ascorbyl free radicals. Ascorbate is the terminal small- molecule antioxidant; the ascorbyl radical is the end-product of higher radical generation and repair, and can be easily detected by our powerful and sophisticated new electron paramagnetic spin resonance technique. This real-time method is ideally suited to demonstrate the role of free radicals in defibrillation injury.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL053284-03
Application #
2430775
Study Section
Surgery and Bioengineering Study Section (SB)
Project Start
1995-07-01
Project End
1999-05-31
Budget Start
1997-06-01
Budget End
1998-05-31
Support Year
3
Fiscal Year
1997
Total Cost
Indirect Cost
Name
University of Iowa
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
041294109
City
Iowa City
State
IA
Country
United States
Zip Code
52242
Clark, Craig B; Zhang, Yi; Martin, Sean M et al. (2004) The nitric oxide synthase inhibitor N(G)-nitro-L-arginine decreases defibrillation-induced free radical generation. Resuscitation 60:351-7
Zhang, Yi; Davies, Loyd R; Martin, Sean M et al. (2003) The nitric oxide donor S-nitroso-N-acetylpenicillamine (SNAP) increases free radical generation and degrades left ventricular function after myocardial ischemia-reperfusion. Resuscitation 59:345-52
Zhang, Yi; Davies, Loyd R; Martin, Sean M et al. (2003) Magnesium reduces free radical concentration and preserves left ventricular function after direct current shocks. Resuscitation 56:199-206
Zhang, Yi; Davies, Loyd R; Coddington, William J et al. (2003) Open-chest epicardial ""surgical"" defibrillation: biphasic versus monophasic waveform shocks. Pacing Clin Electrophysiol 26:711-8
Zhang, Yi; Ramabadran, R S; Boddicker, Kimberly A et al. (2003) Triphasic waveforms are superior to biphasic waveforms for transthoracic defibrillation: experimental studies. J Am Coll Cardiol 42:568-75
Clark, Craig B; Zhang, Yi; Martin, Sean M et al. (2003) The nitric oxide synthase inhibitor N(G)-nitro-L-arginine decreases defibrillation-induced free radical generation. Resuscitation 57:101-8
Oltman, Christine L; Clark, Craig B; Kane, Neal L et al. (2003) Coronary vascular dysfunction associated with direct current shock injury. Basic Res Cardiol 98:406-15
Zhang, Yi; Clark, Craig B; Davies, L Ray et al. (2002) Body weight is a predictor of biphasic shock success for low energy transthoracic defibrillation. Resuscitation 54:281-7
Clark, Craig B; Zhang, Yi; Davies, L Ray et al. (2002) Transthoracic biphasic waveform defibrillation at very high and very low energies: a comparison with monophasic waveforms in an animal model of ventricular fibrillation. Resuscitation 54:183-6
Karlsson, G; Zhang, Y; Davies, L R et al. (2001) Does electrode polarity alter the energy requirements for transthoracic biphasic waveform defibrillation? Experimental studies. Resuscitation 51:77-81

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