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.


METHODS
Prospective, randomized laboratory investigation using an established porcine model with instrumentation for hemodynamic variables, blood gases, and defibrillation attempt.


METHODS
University medical center experimental laboratory.


METHODS
Ten domestic pigs.


METHODS
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.


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.
Krismer
A C
AC
Department of Anesthesiology and Critical Care Medicine, Leopold Franzens University, Innsbruck, Austria.
Lindner
K H
KH
Wenzel
V
V
Rainer
B
B
Mueller
G
G
Lingnau
W
W
D000818:Animals; D001784:Blood Gas Analysis; D001794:Blood Pressure / Q000187:drug effects*; D016887:Cardiopulmonary Resuscitation / Q000379:methods*; D003326:Coronary Circulation / Q000187:drug effects*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D004554:Electric Countershock; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology / Q000627:therapeutic use*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors*; D011446:Prospective Studies; D011897:Random Allocation; D016019:Survival Analysis; D013552:Swine; D013997:Time Factors; D014693:Ventricular Fibrillation / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000503:physiopathology*
D009569:Nitric Oxide; D019331:NG-Nitroarginine Methyl Ester