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 +/- sem coronary perfusion pressure was significantly (p < .05) higher 90 secs (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 +/- sem coronary perfusion pressure remained significantly higher 90 secs 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 CPR was associated with an increase in coronary perfusion pressure and resulted in significantly better initial resuscitation when compared with saline placebo.
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 +/- sem coronary perfusion pressure was significantly (p < .05) higher 90 secs (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 +/- sem coronary perfusion pressure remained significantly higher 90 secs 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 CPR was associated with an increase in coronary perfusion pressure and resulted in significantly better initial resuscitation when compared with saline placebo.
Authors: David G Beiser; Gerasim A Orbelyan; Brendan T Inouye; James G Costakis; Kimm J Hamann; Elizabeth M McNally; Terry L Vanden Hoek Journal: Resuscitation Date: 2010-10-16 Impact factor: 5.262