Noradrenaline and nomega-monomethyl-L-arginine (L-NMMA): effects on haemodynamics and regional blood flow in healthy and septic sheep.
This prospective, non-randomized, controlled experimental study looks at the effects of N(omega)-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.
Booke
M
M
Klinik und Poliklinik für Anästhesiologie und operative Intensivmedizin, Westfälische Wilhelms-Universität Münster, 48129 Münster, Germany.
Hinder
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F
McGuire
R
R
Traber
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LD
Traber
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D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D005260:Female; D006439:Hemodynamics / Q000187:drug effects* / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology*; D010100:Oxygen / Q000378:metabolism; D011446:Prospective Studies; D011550:Pseudomonas aeruginosa; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology; D018805:Sepsis / Q000503:physiopathology*; D012756:Sheep; D014661:Vasoconstriction; D019323:omega-N-Methylarginine / Q000494:pharmacology*
D019323:omega-N-Methylarginine; D010100:Oxygen; D009638:Norepinephrine