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The nitric oxide synthase inhibitor N(G)-nitro-L-arginine decreases defibrillation-induced free radical generation.

Publication ,  Journal Article
Clark, CB; Zhang, Y; Martin, SM; Ray Davies, L; Xu, L; Kregel, KC; Miller, FJ; Buettner, GR; Kerber, RE
Published in: Resuscitation
April 2003

OBJECTIVES: To demonstrate that nitric oxide (NO) contributes to free radical generation after epicardial shocks and to determine the effect of a nitric oxide synthase (NOS) inhibitor, N(G)-nitro-L-arginine (L-NNA), on free radical generation. BACKGROUND: Free radicals are generated by direct current shocks for defibrillation. NO reacts with the superoxide (O(2).(-)) radical to form peroxynitrite (O=NOO(-)), which is toxic and initiates additional free radical generation. The contribution of NO to free radical generation after defibrillation is not fully defined. METHODS AND RESULTS: Fourteen open chest dogs were studied. In the initial eight dogs, 40 J damped sinusoidal monophasic epicardial shocks was administered. Using electron paramagnetic resonance, we monitored the coronary sinus concentration of ascorbate free radical (Ascz.(-)), a measure of free radical generation (total oxidative flux). Epicardial shocks were repeated after L-NNA, 5 mg/kg IV. In six additional dogs, immunohistochemical staining was done to identify nitrotyrosine, a marker of reactive nitrogen species-mediated injury, in post-shock myocardial tissue. Three of these dogs received L-NNA pre-shock. After the initial 40 J shock, Ascz.(-) rose 39+/-2.5% from baseline. After L-NNA infusion, a similar 40 J shock caused Ascz.(-) to increase only 2+/-3% from baseline (P<0.05, post-L-NNA shock versus initial shock). Nitrotyrosine staining was more prominent in control animals than dogs receiving L-NNA, suggesting prevention of O=NOO(-) formation. CONCLUSIONS: NO contributes to free radical generation and nitrosative injury after epicardial shocks; NOS inhibitors decrease radical generation by inhibiting the production of O=NOO(-).

Duke Scholars

Published In

Resuscitation

DOI

ISSN

0300-9572

Publication Date

April 2003

Volume

57

Issue

1

Start / End Page

101 / 108

Location

Ireland

Related Subject Headings

  • Time Factors
  • Sensitivity and Specificity
  • Risk Factors
  • Reference Values
  • Probability
  • Nitroarginine
  • Nitric Oxide Synthase
  • Myocardium
  • Immunohistochemistry
  • Hemodynamics
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Clark, C. B., Zhang, Y., Martin, S. M., Ray Davies, L., Xu, L., Kregel, K. C., … Kerber, R. E. (2003). The nitric oxide synthase inhibitor N(G)-nitro-L-arginine decreases defibrillation-induced free radical generation. Resuscitation, 57(1), 101–108. https://doi.org/10.1016/s0300-9572(02)00413-6
Clark, Craig B., Yi Zhang, Sean M. Martin, L. Ray Davies, Linjing Xu, Kevin C. Kregel, Francis J. Miller, Garry R. Buettner, and Richard E. Kerber. “The nitric oxide synthase inhibitor N(G)-nitro-L-arginine decreases defibrillation-induced free radical generation.Resuscitation 57, no. 1 (April 2003): 101–8. https://doi.org/10.1016/s0300-9572(02)00413-6.
Clark CB, Zhang Y, Martin SM, Ray Davies L, Xu L, Kregel KC, et al. The nitric oxide synthase inhibitor N(G)-nitro-L-arginine decreases defibrillation-induced free radical generation. Resuscitation. 2003 Apr;57(1):101–8.
Clark, Craig B., et al. “The nitric oxide synthase inhibitor N(G)-nitro-L-arginine decreases defibrillation-induced free radical generation.Resuscitation, vol. 57, no. 1, Apr. 2003, pp. 101–08. Pubmed, doi:10.1016/s0300-9572(02)00413-6.
Clark CB, Zhang Y, Martin SM, Ray Davies L, Xu L, Kregel KC, Miller FJ, Buettner GR, Kerber RE. The nitric oxide synthase inhibitor N(G)-nitro-L-arginine decreases defibrillation-induced free radical generation. Resuscitation. 2003 Apr;57(1):101–108.
Journal cover image

Published In

Resuscitation

DOI

ISSN

0300-9572

Publication Date

April 2003

Volume

57

Issue

1

Start / End Page

101 / 108

Location

Ireland

Related Subject Headings

  • Time Factors
  • Sensitivity and Specificity
  • Risk Factors
  • Reference Values
  • Probability
  • Nitroarginine
  • Nitric Oxide Synthase
  • Myocardium
  • Immunohistochemistry
  • Hemodynamics