Modulation of systemic hemodynamics by exogenous L-arginine in normal and bacteremic sheep
作者:
José,
Lorente Miguel,
Delgado Carmen,
Tejedor Enrique,
Mon Mónica,
Hervás Tomás,
Pascual Pilar,
Fernández-Segoviano Gloria,
Rieppi Alberto,
Soler Diego,
Ayuso Andrés,
期刊:
Critical Care Medicine
(OVID Available online 1999)
卷期:
Volume 27,
issue 11
页码: 2474-2479
ISSN:0090-3493
年代: 1999
出版商: OVID
关键词: sepsis;vascular reactivity;hemodynamic;L-arginine;sheep
数据来源: OVID
摘要:
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 ofEscherichia coli(1.5 × 108colony-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 ofE. coliand 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.
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