The hemodynamic effects of inhaled nitric oxide and endogenous nitric oxide synthesis blockade in newborn piglets during infusion of heat-killed group B streptococci

Objective: To determine the effects of therapy with inhaled nitric oxide (N O) gas and partial or complete blockade of endogenous NO synthesis with N-o mega-nitro-L-arginine (L-NA) on the hemodynamic responses to group B strept ococci infusion in newborn piglets. Design: Randomized, acute intervention study. Setting: Animal research laboratory. Subjects: Twenty-five anesthetized piglets younger than 3 days of age divid ed into five groups. Interventions: Heat-killed group B streptococci (GBS) were infused systemic ally until a 50% increase in pulmonary artery pressure (PAP) was obtained, and the infusion was continued for another 2 hrs. The five groups were desi gned as follows: group 1, sepsis control: continuous GBS infusion, with two brief trials (10 mins) of inhaled NO given after the initial development o f pulmonary hypertension and again 2 hrs later; group 2, continuous inhaled NO: NO was given at 40 ppm for 2 hrs during GBS infusion; group 3, high-do se L-NA pretreatment: 10 mg/kg L-NA bolus followed by 1 mg/kg/min before, a nd continuing throughout, GBS infusion; group 4, high-dose L-NA: same dose as in group 3, but given after the start of the GBS infusion with continuou s inhaled NO at 40 ppm; and group 5, low-dose L-NA: 3 mg/kg bolus given aft er start of GBS infusion with continuous inhaled NO at 40 ppm. Measurements and Main Results: The sepsis controls, group 1, had an increas e in PAP, which took 15-45 mins to develop, from a mean of 3.4 (SD 0.7) to 5.9 (1.9) kPa (p < .05), at which time the cardiac index had decreased from 169 (28) to 146 (46) mL/kg/min (p < .05). Brief inhaled NO during the earl y phase decreased PAP to normal. Two hours later, PAP had increased to 6.1 (0.2) kPa and cardiac index had decreased to 88 (31) mL/kg/min. Inhaled NO after 2 hrs decreased PAP to 3.2 (0.5) kPa and increased cardiac index to 1 06 (44) mL/kg/min (p < .05). Continuous inhaled NO (group 2) ameliorated th e deterioration in cardiac index, which at 2 hrs was 140 (30) mL/kg/min (si gnificantly greater than in the sepsis controls) (p < .05). The L-NA-pretre ated animals (group 3) had a greater increase in PAP and pulmonary vascular resistance index when GBS infusion was started. PAP increased from 3.0 (0. 7) to 7.3 (1.5) kPa within 15 mins, and cardiac index simultaneously decrea sed to 68 (20) mL/kg/min. Cardiac index subsequently rapidly deteriorated t o 48 (21) mL/kg/min, and only one of five animals survived for 2 hrs. Group 4 animals also developed a rapid deterioration in cardiac output, and only two of five survived for 2 hrs. Group 5 animals had results indistinguisha ble from group 2 animals. Conclusion: Pulmonary hypertension and shack resulting from GBS infusion in newborn piglets are much worse if endogenous NO production is completely i nhibited. Continuous inhaled NO with or without low-dose L-NA inhibits the decrease in cardiac output.