This prospective, non-randomized, controlled experimental study looks at the effects of NΩ-monomethyl-l-arginine (l-NMMA) on haemodynamics, oxygen transport and regional blood flow in healthy and septic sheep, and compares these effects with those of noradrenaline (NA; norepinephrine). All sheep were chronically instrumented. Six sheep received l-NMMA (7 mg·kg-1·h-1), six sheep received NA, and seven sheep received the carrier alone (0.9% NaCl). The NA dosage was continuously and individually adjusted to achieve the same increase in blood pressure as observed in matched sheep of the l-NMMA group (non-septic phase). Treatment was discontinued after 3 h. Sepsis was initiated and maintained by a continuous infusion of live Pseudomonas aeruginosa. After 24 h of sepsis, the sheep were again challenged over a treatment period of 3 h with their previously assigned drug (septic phase). During the non-septic phase of the experiment, NA and l-NMMA both caused an increase in mean arterial pressure (MAP) through vasoconstriction. Ater 24 h of sepsis, all sheep developed a hyperdynamic circulatory state. While l-NMMA caused an increase in MAP through intense vasoconstriction, NA caused MAP to increase through a further elevation of the cardiac index. The NA dosage needed was significantly higher in the septic phase compared with the non-septic phase, reflecting a reduced vascular responsiveness to catecholamines during sepsis. Renal blood flow remained unchanged during either treatment in both the non-septic and the septic phases. Nevertheless, urine output increased during NA treatment in both the non-septic and the septic phases, while l-NMMA caused urine output to increase only under septic conditions.
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January 11 2000
Noradrenaline and Nω-monomethyl-L-arginine (L-NMMA): effects on haemodynamics and regional blood flow in healthy and septic sheep
M. BOOKE;
M. BOOKE
*Klinik und Poliklinik für Anästhesiologie und operative Intensivmedizin, Westfälische Wilhelms-Universität Münster, 48129 Münster, Germany
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F. HINDER;
F. HINDER
*Klinik und Poliklinik für Anästhesiologie und operative Intensivmedizin, Westfälische Wilhelms-Universität Münster, 48129 Münster, Germany
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R. MCGUIRE;
R. MCGUIRE
†Department of Anesthesiology, The University of Texas Medical Branch, Galveston, TX 77555-0833, U.S.A.
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L. D. TRABER;
L. D. TRABER
†Department of Anesthesiology, The University of Texas Medical Branch, Galveston, TX 77555-0833, U.S.A.
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D. L. TRABER
†Department of Anesthesiology, The University of Texas Medical Branch, Galveston, TX 77555-0833, U.S.A.
Correspondence: Dr Daniel L. Traber (e-mail [email protected]).
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Publisher: Portland Press Ltd
Received:
April 20 1999
Revision Received:
September 02 1999
Accepted:
October 27 1999
Online ISSN: 1470-8736
Print ISSN: 0143-5221
The Biochemical Society and the Medical Research Society © 2000
2000
Clin Sci (Lond) (2000) 98 (2): 193–200.
Article history
Received:
April 20 1999
Revision Received:
September 02 1999
Accepted:
October 27 1999
Citation
M. BOOKE, F. HINDER, R. MCGUIRE, L. D. TRABER, D. L. TRABER; Noradrenaline and Nω-monomethyl-L-arginine (L-NMMA): effects on haemodynamics and regional blood flow in healthy and septic sheep. Clin Sci (Lond) 1 February 2000; 98 (2): 193–200. doi: https://doi.org/10.1042/cs0980193
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