Abstract 75: Cardiac-Specific NOS3 Overexpression Rescues Myocardial and Neuronal Function after Cardiopulmonary Resuscitation in NOS3-Deficient Mice
Backgound: To elucidate the role of NOS3 in the recovery from cardiac arrest and CPR, we studied the impact of varying levels of cardiac NOS3 expression on neurological and myocardial function after cardiac arrest and CPR in wild-type C57BL/6 mice (WT, n=7), NOS3-deficient mice (NOS3−/−, n=8), and NOS3−/− mice with cardiomyocyte-restricted overexpression of NOS3 (NOS3−/−TG, n=7).
Methods: Mice were subjected to potassium-induced cardiac arrest for 9 min with mild hypothermia (~30°C) whereupon CPR was attempted with chest compression and mechanical ventilation. Cardiac function was examined with a pressure-volume catheter 18h after CPR in anesthetized mice and compared with mice of that were not subjected to cardiac arrest (n=4 for each genotype). Neurological function was assessed by a scoring system (walking, corneal reflex, reflex to painful stimuli, respiration, and general appearance).
Results: Pre-arrest myocardial function was similar between genotypes except that LV end-systolic pressure was higher in NOS3−/− and NOS3−/−TG than in WT. 18h after CPR, LV ejection fraction (EF) and maximal rate of LV pressure rise (dP/dtmax) decreased markedly in NOS3−/− but not in WT and NOS3−/−TG (Table⇓). Load-independent measures of LV contractile function including preload-recruitable stroke work (PRSW) and end-systolic elastance (Ees) were markedly impaired in NOS3−/− but not in WT and NOS3−/−TG. Neurological function score was lower in NOS3−/− compared to WT and NOS3−/−TG. While the rate of successful restoration of spontaneous circulation was similar between the genotypes, survival rate at 18h after CPR tended to be less in NOS3−/− compared to WT and NOS3−/−TG.
Conclusion: These results demonstrate that cardiomyocyte-specific NOS3 overexpression rescues myocardial and neuronal function after cardiopulmonary resuscitation in NOS3-deficient mice.