Comparison of the haemodynamic effects of nitric oxide synthase inhibition and nitric oxide scavenging in endotoxaemic sheep.
OBJECTIVE
The present study compared the effects of nitric oxide (NO) synthase inhibition and NO scavenging with haemoglobin in endotoxaemic sheep.


METHODS
12 sheep were instrumented for chronic study. Six sheep received LG-nitro-arginine-methylester (L-NAME, 2.5 mg/kg bolus followed by a continuous infusion of 0.5 mg/kg per h), the other 6 sheep received pyridoxalated haemoglobin polyoxyethylene conjugate (PHP, 100 mg/kg bolus followed by a continuous infusion of 20 mg/kg per h).


RESULTS
Haemodynamic and oxygenation parameters were measured in healthy sheep, after infusion of Salmonella typhosa endotoxin (10 ng/kg per min) for 24 h and after infusion of L-NAME or PHP. The infusion of endotoxin resulted in a hypotensive, hyperdynamic circulation. Infusion of L-NAME increased mean arterial pressure (MAP) from 76.1 +/- 4.2 mmHg to normal values of 95.8 +/- 5.7 mmHg (p < 0.05). PHP increased MAP from 73.0 +/- 3.0 to 88.6 +/- 4.7 mmHg (p < 0.05). This increase in MAP was associated in the L-NAME group with a more prominent drop in cardiac index (from 10.2 +/- 0.4 to 7.0 +/- 0.51.min-1.m-2; p < 0.05) than in the PHP group (from 10.7 +/- 0.2 to 9.3 +/- 0.61.min-1.m-2). During the first 90 min of infusion, cardiac index remained lower in the L-NAME group than in the PHP group. The increase in pulmonary vascular resistance was also higher in the L-NAME group.


CONCLUSIONS
These results suggest, that at the doses used in the experiment, NO scavenging with PHP has smaller effects on cardiac index and pulmonary vascular resistance than NO synthase inhibition with L-NAME. Therefore, the concept of NO scavenging in hyperdynamic sepsis should be further evaluated.
Bone
H G
HG
Klinik und Poliklinik für Anästhesiologie und operative Intensivmedizin, Münster, Germany. bone@uni-muenster.de
Waurick
R
R
Van Aken
H
H
Booke
M
M
Prien
T
T
Meyer
J
J
D000818:Animals; D019446:Endotoxemia / Q000188:drug therapy* / Q000382:microbiology; D004791:Enzyme Inhibitors / Q000493:pharmacokinetics* / Q000627:therapeutic use; D006439:Hemodynamics; D006454:Hemoglobins / Q000378:metabolism* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019331:NG-Nitroarginine Methyl Ester / Q000493:pharmacokinetics* / Q000627:therapeutic use; D010101:Oxygen Consumption; D011092:Polyethylene Glycols / Q000493:pharmacokinetics* / Q000627:therapeutic use; D012485:Salmonella typhi / Q000187:drug effects; D012756:Sheep; D014435:Typhoid Fever / Q000188:drug therapy / Q000382:microbiology
D004791:Enzyme Inhibitors; D006454:Hemoglobins; C050907:pyridoxalated-hemoglobin-polyethylene glycol conjugate; D011092:Polyethylene Glycols; D019331:NG-Nitroarginine Methyl Ester