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

Resuscitation. 2003 Apr;57(1):101-8. doi: 10.1016/s0300-9572(02)00413-6.

Abstract

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(-).

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Disease Models, Animal
  • Dogs
  • Electric Countershock / adverse effects*
  • Electric Countershock / methods
  • Electron Spin Resonance Spectroscopy
  • Enzyme Inhibitors / pharmacology*
  • Free Radicals / metabolism*
  • Hemodynamics / physiology
  • Immunohistochemistry
  • Myocardium / pathology*
  • Nitric Oxide Synthase / drug effects*
  • Nitric Oxide Synthase / metabolism
  • Nitroarginine / pharmacology*
  • Probability
  • Reference Values
  • Risk Factors
  • Sensitivity and Specificity
  • Time Factors

Substances

  • Enzyme Inhibitors
  • Free Radicals
  • Nitroarginine
  • Nitric Oxide Synthase