Modulation of systemic hemodynamics by exogenous L-arginine in normal and bacteremic sheep.
OBJECTIVE: To investigate whether exogenous L-arginine, the substrate for nitric oxide synthase, modulates systemic hemodynamics in sepsis. DESIGN: Prospective, controlled study in a sheep model of sepsis. SETTING: Animal research facility in a university hospital. SUBJECTS: Adult sheep weighing between 35 and 55 kg. INTERVENTIONS: Adult sheep sedated and mechanically ventilated, were monitored with a pulmonary arterial catheter and an ileal tonometer. Four groups of sheep were studied: nonseptic, septic, nonseptic treated with L-arginine, and septic treated with L-arginine. Sepsis was induced by the intravenous administration of Escherichia coli (1.5x10(8) colony-forming units/kg for 30 mins). L-arginine was administered as an intravenous bolus (200 mg/kg for 10 mins) before the septic challenge followed by 200 mg/kg/hr for 300 mins. MEASUREMENTS AND MAIN RESULTS: Sepsis induced a state of acidosis, hyperlactatemia, hypoxemia, and gastric intramucosal acidosis. During the first 30 mins after the septic challenge, there was a decrease in cardiac index and blood pressure, and an increase in systemic vascular resistance. Thereafter, blood pressure returned to baseline values, and systemic vascular resistance fell. Treatment with L-arginine in nonseptic sheep did not induce any biochemical or hemodynamic effect. In septic sheep, treatment with L-arginine was associated with a greater increase in systemic vascular resistance during the first 30 mins, and a more marked decrease in blood pressure and systemic vascular resistance after 180 mins. CONCLUSIONS: Exogenous administration of L-arginine does not induce hemodynamic effects in normal animals, exacerbates the acute vasoconstriction associated with the intravenous infusion of E. coli and potentiates the sepsis-induced vasodilation. Our results suggest that a) nitric oxide production is not constitutively modulated by exogenous L-arginine, b) L-arginine probably enhances the sepsis-induced sympathetic discharge, and c) L-arginine becomes rate-limiting for the formation of nitric oxide at approximately 3 hrs after the initiation of the septic challenge.[1]References
- Modulation of systemic hemodynamics by exogenous L-arginine in normal and bacteremic sheep. Lorente, J.A., Delgado, M.A., Tejedor, C., Mon, E., Hervás, M., Pascual, T., Fernández-Segoviano, P., Rieppi, G., Soler, A., Ayuso, D., Esteban, A. Crit. Care Med. (1999) [Pubmed]
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