Cardiopulmonary effects of combined nitric oxide inhibition and inhaled nitric oxide in porcine endotoxic shock.
BACKGROUND
Nitric oxide synthase (NOS) inhibition has been shown to potentiate lipopolysaccharide (LPS) associated pulmonary hypertension, which may worsen right ventricular (RV) dysfunction and decrease cardiac output during sepsis. This study evaluates whether inhaled nitric oxide can ameliorate the adverse cardiopulmonary effects of NOS inhibition during endotoxemia.


METHODS
After an infusion of Escherichia coli LPS (200 micrograms/kg), animals were resuscitated with saline (1 mL/kg/min) and observed for 3 hours while mechanically ventilated (FIO2, 0.6; VT, 12 mL/kg; positive end-expiratory pressure, 5 cm H2O). The LPS group (n = 6) received no additional treatment. The N-nitro-L-arginine methyl ester (NAME) group (n = 5) received L-NAME, a NOS inhibitor, 50 micrograms/kg/min for the last 2 hours. The NO+NAME group (n = 6) received inhaled NO (40 ppm) and L-NAME for the last 2 hours. The control group (n = 5) received only saline without LPS. Hemodynamic data and blood gases were collected hourly for 3 hours.


RESULTS
L-NAME worsened LPS-associated pulmonary hypertension and RV dysfunction as reflected by decreased RV ejection fraction. Inhaled nitric oxide significantly decreased pulmonary hypertension and improved RV ejection fraction and stroke work index. There were no adverse systemic effects.


CONCLUSIONS
Inhaled nitric oxide reverses pulmonary hypertension seen with L-NAME treatment during endotoxemia and may be a useful adjunct to NOS inhibition in the treatment of septic shock.
Offner
P J
PJ
Department of Surgery, Brooke Army Medical Center, Fort Sam Houston, Texas, USA.
Ogura
H
H
Jordan
B S
BS
Pruitt
B A
BA
Cioffi
W G
WG
D000280:Administration, Inhalation; D000818:Animals; D019446:Endotoxemia / Q000201:enzymology / Q000503:physiopathology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006439:Hemodynamics / Q000187:drug effects; D006976:Hypertension, Pulmonary / Q000188:drug therapy / Q000503:physiopathology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000008:administration & dosage / Q000627:therapeutic use*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000502:physiology*; D012119:Respiration / Q000187:drug effects* / Q000502:physiology; D012772:Shock, Septic / Q000188:drug therapy / Q000503:physiopathology; D013552:Swine
D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester