Comparison of the haemodynamic effects of nitric oxide synthase inhibition and nitric oxide scavenging in endotoxaemic sheep

Abstract

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 l ^G-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 ± 0.5 l · min^–1· m^–2; p < 0.05) than in the PHP group (from 10.7 ± 0.2 to 9.3 ± 0.6 l · 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.