Ischemic tissues generate
nitric oxide (NO) by direct reduction of tissue
nitrite under the acidic conditions that occur during
ischemia. In view of the important implications of this
enzyme-independent mechanism of NO generation on the pathogenesis and treatment of tissue injury, the NO formation in mice subjected to
cardiopulmonary arrest was measured and imaged. Real-time measurement of NO generation was performed by detection of naturally generated NO-
heme complexes in tissues using L-band electron paramagnetic resonance (EPR) spectroscopy. To distinguish NO generated from
nitrite, animals were labeled with isotopically enriched (15)N-nitrite. Mice were infused with
nitrite (70 mg/kg, intravenous),
cardiopulmonary arrest induced by an overdose of
phenobarbital, and transferred to the EPR resonator. Measurements of NO generation were performed on the intact animal at the levels of the head, thorax, and abdomen. At the end of 3 hr, major organs were isolated and analyzed for their NO signal. The NO complexes were found to have maximum levels in lung, heart, and liver. Three-dimensional spatial mapping of the NO complex in the intact animal subjected to
cardiopulmonary arrest was performed using EPR imaging techniques. The images also confirmed the maximum formation in the lungs, heart, and liver. The present data reveal that mice subjected to
cardiopulmonary arrest generate large amounts of NO, which is
nitrite mediated. The observed signal was largely due to
heme-bound NO, which accounted for the high concentrations found in these organs. This increased NO formation during
cardiopulmonary arrest could contribute to the difficulty of
resuscitation after long periods of arrest. Magn Reson Med 45:700-707, 2001.