L-ARGININE PATHWAY IN THE SEPSIS SYNDROME

Objective: To investigate the role of nitric oxide in the regulation o f vascular tone in patients with the sepsis syndrome. Design: Prospect ive, intervention study. Setting. Tertiary care hospital. Patients. Fi fteen patients admitted to our medical intensive care unit with the di agnosis of sepsis syndrome by defined criteria. Interventions: Eight p atients received N(omega)-nitro-L-arginine (20 mg/kg, iv bolus) follow ed by L-arginine (200 mg/kg, iv bolus). Seven patients received L-argi nine alone (200 mg/kg). Measurements and Main Results: In the first gr oup, hemodynamic and oxygen transport variables were recorded at basel ine, during 45 mins after the injection of N(omega)-nitro-L-arginine, and during 45 mins after the administration of L-arginine. In the seco nd 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 hyper tension (mean blood pressure increased from 89 +/- 8 to a maximum of 1 40 +/- 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 r ight 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 patient s 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/m in/m2). Both systemic and pulmonary vascular resistance indices decrea sed (from 1987.6 +/- 163.9 to 1251.4 +/- 231.5 dyne-sec/cm5.m2, and fr om 486.1 +/- 65.2 to 380.5 +/- 70.3 dyne . sec/cm5.m2). Parallel to th e increase in oxygen transport due to the increase in cardiac output, oxygen consumption index increased significantly 1 min after L-arginin e (from 127.0 +/- 19.0 to 182.5 +/- 37.3 mL/min/m2). All mentioned cha nges were statistically significant (p <.05). Conclusions: A continuou s basal release of nitric oxide plays a role in the regulation of syst emic and pulmonary vascular tone in patients with sepsis syndrome. L-a rginine has systemic and pulmonary vasodilatory actions.