Intensive care medicine · 1998
Comparison of the haemodynamic effects of nitric oxide synthase inhibition and nitric oxide scavenging in endotoxaemic sheep.
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Bone H G, Waurick R, Van Aken H, Booke M, Prien T, Meyer J
Аннотация
OBJECTIVE: The present study compared the effects of nitric oxide (NO) synthase inhibition and NO scavenging with haemoglobin in endotoxaemic sheep.
DESIGN: 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).
MEASUREMENTS AND 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.
CONCLUSION: 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.
DESIGN: 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).
MEASUREMENTS AND 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.
CONCLUSION: 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.