Objective: The role of nitric oxide during neonatal sepsis is complex. The present study tests the hypothesis that nonselective inhibition of nitric oxide synthase (NOS) with N-nitro-L-arginine methyl ester (LNAME) is detrimental during the early phase of experimental E. coli sepsis in newborn piglet.

Methods: A total of 35 ventilated piglets (<3days-old) were divided into four groups: Gr. 1 (control, n=6) given normal saline 1 ml iv; Gr. 2 (NAME control, n=6) given 10 mg/kg of LNAME iv; Gr. 3 (E. coli, n=12) had 1 ml E. coli strain 69 (109 cfu) iv; and Gr. 4 (E. coli + NAME, n=11) given LNAME 10 mg/kg iv 1 hour prior to E. coli injection. Hemodynamic changes were monitored for 4 hours. CBC, PT, aPTT, serum lactate and TNF levels (0 hour, 2 hour, at the end), and plasma levels of factor 1, 8, thrombin-antithrombin complexes (TAT), antithrombin III activity (AT III), tissue plasminogen activator (tPA), plasminogen activator inhibitor (PAI) and von Willebrand factor (vWF) (0 hour, at the end) were measured.

Results: Survival of piglets at the 4th hour was 27.3% in Gr. 4(3/11) and 100% in others (p<0.01). BP decreased after E. coli injection(Grs. 3 & 4) and more profoundly decreased in Gr. 4. In Gr. 4, PaO2/FiO2 ratio decreased, blood lactate levels increased progressively and both were significantly different at the end of the study compared to other Groups. Peak serum TNF levels were not different between Gr. 3 and 4. Final levels of factor 1, 8, ATIII, tPA, PAI, and vWF were not different among all four Groups.

Conclusion: Results of our study suggest that nonselective inhibition of NOS is detrimental by induction of intravascular coagulation during the early phase of E. Coli sepsis in newborn piglet. We speculate that nonselective inhibition of NOS during neonatal sepsis aggravates multi-organ system dysfunction due to enhanced disseminated intravascular coagulation. Table

Table 1 No caption available.
Full size table