Inhibition of nitric oxide improves coronary perfusion pressure and return of spontaneous circulation in a porcine cardiopulmonary resuscitation model

Objective: During spontaneous circulation, nonspecific inhibition of nitric oxide synthase by N-G-nitro-L-arginine methyl ester (L-NAME) increases systemic vascular resistance and, therefore, mean arterial pressure. If this effect can be extrapolated to cardiopulmonary resuscitation (CPR), administering L-NAME during CPR may be beneficial by maintaining or even improving coronary perfusion pressure, and hence successful defibrillation. Design: Prospective, randomized laboratory investigation using an established porcine model with instrumentation for hemodynamic variables, blood gases, and defibrillation attempt. Setting: University medical center experimental laboratory. Subjects: Ten domestic pigs. Interventions: After 4 mins of ventricular fibrillation, ten animals were randomly assigned to receive L-NAME (25 mg/kg; n = 5) or saline placebo (n = 5) (given in two doses) after 3 and 13 mins of CPR, respectively. Defibrillation was provided 5 mins after the second dose of active drug or placebo. Measurements and Main Results: Mean a SEM coronary perfusion pressure was significantly (p < .05) higher 90 sees (27 +/- 3 vs. 17 +/- 3 mm Hg), 10 mins (28 +/- 3 vs. 14 +/- 2 mm Hg), and 15 mins (21 +/- 5 vs. 7 +/- 3 mm Hg) after the first L-NAME administration compared with saline placebo. Mean a SEM coronary perfusion pressure remained significantly higher 90 sees and 5 mins after the second L-NAME vs. saline placebo administration (19 +/- 4 vs. 6 +/- 4 mm Hg, and 17 +/- 3 vs. 4 +/- 4 mm Hg). After 22 mins of cardiac arrest, including 18 mins of CPR, four of five pigs in the L-NAME group were successfully defibrillated, and survived the 60-min postresuscitation phase, In the placebo group, none of five pigs could be defibrillated successfully (p < .05). Conclusions: Nonspecific blockade of nitric oxide synthase with L-NAME during GPR was associated with an increase in coronary perfusion pressure and resulted in significantly better initial resuscitation when compared with saline placebo.