Abstract 15606: Inhaled Nitric Oxide Improves Long-term Outcome After Successful Cardiopulmonary Resuscitation in Mice
Introduction: Deficiency of nitric oxide synthase 3 (NOS3) or soluble guanylate cyclase α1 (sGCα1, a primary target of NO) worsens outcomes after CA/CPR in mice. While these results suggest protective effects of NO-sGC-cGMP dependent mechanisms on the outcomes of CA/CPR, systemic administration of NO-donor compounds may induce systemic vasodilation and hypotension. We hypothesized that inhaled NO improves long-term outcome of CA/CPR.
Methods: Adult male mice were subjected to potassium-induced CA for 7.5 min at 37°C whereupon CPR was performed with chest compression and mechanical ventilation. One hour after CPR, mice were extubated and breathed 40 ppm NO mixed in air (iNO, n=13) or air alone (Control, n=13) for 23h. Survival was observed up to 10 days. Neurological and LV function and brain caspase-3 activation were examined 4 days after CPR. Serum NOx levels were measured at 24h and phosphorylation of vasodilator-stimulated phosphoprotein (VASP, a target of cGMP-dependent protein kinase) was assessed 2h after CPR in the lung. To define the role of sGC on effects of inhaled NO on the outcome of CA/CPR, sGCα1 deficient mice were subjected to CA/CPR with or without NO inhalation.
Results: Mice that were subjected to CA/CPR and breathed air exhibited poor long-term survival rate (4/13), depressed neurological and LV function, and increased caspase-3 activation in the brain cortex. Inhaled NO starting 1h after CPR markedly improved survival rate 10 days after CPR (11/13, P<0.01 vs Control). Inhaled NO attenuated neurological and LV dysfunction and prevented caspase-3 activation in the brain cortex. The protective effects of inhaled NO on the outcome of CA/CPR were associated with increased serum NOx levels and VASP phosphorylation in the lung. Deficiency of sGCα1 abrogated the ability of inhaled NO to improve outcome of CA/CPR.
Conclusion: These results suggest that NO inhalation after successful CPR improves long-term outcome after CA via sGC-dependent mechanisms.
- © 2010 by American Heart Association, Inc.