Abstract 15842: Inhaled Nitric Oxide Improves Outcomes After Cardiac Arrest and Cardiopulmonary Resuscitation Above and Beyond Therapeutic Hypothermia in Mice
Background: We previously reported that inhaled nitric oxide (NO) improves outcomes after cardiac arrest (CA) and CPR in mice. Therapeutic hypothermia (TH) improves neurological outcomes after CA. In this study, we examined whether or not NO inhalation combined with TH improves outcomes after CA/CPR compared with TH alone. We also examined role of endogenous NO on the beneficial effects of TH on the outcomes after CA/CPR.
Methods: Wild-type (WT) mice and mice deficient for NOS3 (NOS3-/-) were subjected to CA at 37°C and CPR was performed with chest compression. Body temperature was maintained at 37°C (Normothermia) or reduced to 33°C (TH) for 24h. TH-treated mice breathed air or air mixed with NO at 10, 20, 40, 60, or 80 ppm. Effects of inhaled NO on cerebral blood flow (CBF) were assessed by arterial spin labeling with MRI. Expression of phosphorylated NOS3 was examined in brain cortex 3h after CA/CPR in WT mice treated with or without TH.
Results: Inhalation of NO at 40 or 60 ppm, concurrently administered with TH, markedly improved the survival rate in WT mice compared to TH alone. Inhaled NO initiated at 30 min and 2h, but not 6h, after CA/CPR combined with TH further improved survival rate of WT mice compared with TH alone. NO breathing combined with TH prevented brain injury without affecting CBF after CA/CPR. TH increased phospho-NOS3Ser1177 and decreased phospho-NOS3Thr495 in the brain cortex of WT mice after CA/CPR. Hypothermia failed to improve the survival rate in NOS3-/- mice subjected to CA/CPR. Breathing NO during hypothermia rescued NOS3-/- mice after CA/CPR.
Conclusions: Inhaled NO during TH remains beneficial and further improves outcomes after CA/CPR compared to TH alone. NOS3-derived NO importantly contributes to the beneficial effects of TH after CA/CPR. NO breathing restores the ability of TH to improve outcomes after CA/CPR when endogenous NO production is impaired.
- © 2013 by American Heart Association, Inc.