1. Comparison of the haemodynamic effects of nitric oxide synthase inhibition and nitric oxide scavenging in endotoxaemic sheep
- Author
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Bone, H. G., Waurick, R., Van Aken, H., Booke, M., Prien, T., and Meyer, J.
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Hemodynamics -- Observations ,Nitric oxide -- Health aspects ,Septic shock -- Research ,Health care industry - Abstract
Byline: H. G. Bone (1), R. Waurick (1), H. Van Aken (1), M. Booke (1), T. Prien (1), J. Meyer (1) Keywords: Key words Endotoxaemia; Sepsis; Nitric oxide; Haemoglobin 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 .sup.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.sup.--1* m.sup.--2 p < 0.05) than in the PHP group (from 10.7 +- 0.2 to 9.3 +- 0.6 l * min.sup.--1* m.sup.--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. Author Affiliation: (1) Klinik und Poliklinik fur Anasthesiologie und operative Intensivmedizin, Albert-Schweitzer-Strasse 33, D-48129 Munster, Germany Fax: + 49 (251) 8 87 04 E-mail: bone@uni-muenster.de, DE Article note: Received: 29 January 1997 Accepted: 23 October 1997
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- 1998