Noradrenaline and Nω-monomethyl-L-arginine (L-NMMA): effects on haemodynamics and regional blood flow in healthy and septic sheep

Abstract

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.