L-arginine pathway in the sepsis syndrome

Abstract

OBJECTIVE: To investigate the role of nitric oxide in the regulation of vascular tone in patients with the sepsis syndrome. DESIGN: Prospective, intervention study. SETTING: Tertiary care hospital. PATIENTS: Fifteen patients admitted to our medical intensive care unit with the diagnosis of sepsis syndrome by defined criteria. INTERVENTIONS: Eight patients received N omega-nitro-L-arginine (20 mg/kg, iv bolus) followed by L-arginine (200 mg/kg, iv bolus). Seven patients received L-arginine alone (200 mg/kg). MEASUREMENTS AND MAIN RESULTS: In the first group, hemodynamic and oxygen transport variables were recorded at baseline, during 45 mins after the injection of N omega-nitro-L-arginine, and during 45 mins after the administration of L-arginine. In the second group, hemodynamic parameters were recorded at baseline and during 15 mins after the administration of L-arginine. Data are mean +/- SEM. The administration of N omega-nitro-L-arginine was followed by hypertension (mean blood pressure increased from 89 +/- 8 to a maximum of 140 +/- 12 mm Hg) accompanied by a decrease in cardiac index (from 3.51 +/- 0.39 to a minimum of 2.65 +/- 0.21 L/min/m2) and an increase in right atrial and pulmonary artery occlusion pressure. Systemic vascular resistance index increased from 1871.1 +/- 302.3 to 3825.6 +/- 244.4 dyne.sec/cm5.m2, and pulmonary vascular resistance increased from 533.2 +/- 125.8 to 816.0 +/- 117.3 dyne.sec/cm5.m2. These changes induced by N omega-nitro-L-arginine were reversed by the administration of L-arginine. The administration of L-arginine to another group of patients caused transient hypotension (from 103 +/- 6 to 81 +/- 10 mm Hg) and an increase in cardiac index (from 3.57 +/- 0.15 to 4.74 +/- 0.54 L/min/m2). Both systemic and pulmonary vascular resistance indices decreased (from 1987.6 +/- 163.9 to 1251.4 +/- 231.5 dyne.sec/cm5.m2, and from 486.1 +/- 65.2 to 380.5 +/- 70.3 dyne.sec/cm5.m2). Parallel to the increase in oxygen transport due to the increase in cardiac output, oxygen consumption index increased significantly 1 min after L-arginine (from 127.0 +/- 19.0 to 182.5 +/- 37.3 mL/min/m2). All mentioned changes were statistically significant (p < .05). CONCLUSIONS: A continuous basal release of nitric oxide plays a role in the regulation of systemic and pulmonary vascular tone in patients with sepsis syndrome. L-arginine has systemic and pulmonary vasodilatory actions.