title: The hemodynamic effects of inhaled nitric oxide and endogenous nitric oxide synthesis blockade in newborn piglets during infusion of heat-killed group B streptococci.
abstract: OBJECTIVE
  To determine the effects of therapy with inhaled nitric oxide (NO) gas and partial or complete blockade of endogenous NO synthesis with N(omega)nitro-L-arginine (L-NA) on the hemodynamic responses to group B streptococci infusion in newborn piglets.
  
  
  METHODS
  Randomized, acute intervention study.
  
  
  METHODS
  Animal research laboratory.
  
  
  METHODS
  Twenty-five anesthetized piglets younger than 3 days of age divided into five groups.
  
  
  METHODS
  Heat-killed group B streptococci (GBS) were infused systemically until a 50% increase in pulmonary artery pressure (PAP) was obtained, and the infusion was continued for another 2 hrs. The five groups were designed as follows: group 1, sepsis control: continuous GBS infusion, with two brief trials (10 mins) of inhaled NO given after the initial development of 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-dose L-NA pretreatment: 10 mg/kg L-NA bolus followed by 1 mg/kg/min before, and 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 continuous inhaled NO at 40 ppm; and group 5, low-dose L-NA: 3 mg/kg bolus given after start of GBS infusion with continuous inhaled NO at 40 ppm.
  
  
  RESULTS
  The sepsis controls, group 1, had an increase 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 early 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 106 (44) ml/kg/min (p < .05). Continuous inhaled NO (group 2) ameliorated the deterioration in cardiac index, which at 2 hrs was 140 (30) mL/kg/min (significantly greater than in the sepsis controls) (p < .05). The L-NA-pretreated 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 decreased to 68 (20) mL/kg/min. Cardiac index subsequently rapidly deteriorated to 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 indistinguishable from group 2 animals.
  
  
  CONCLUSIONS
  Pulmonary hypertension and shock resulting from GBS infusion in newborn piglets are much worse if endogenous NO production is completely inhibited. Continuous inhaled NO with or without low-dose L-NA inhibits the decrease in cardiac output.
authors.affiliation: Perinatal Research Centre, University of Alberta, Canada.
authors.forename: K J
authors.initials: KJ
authors.lastname: Barrington
authors.forename: P C
authors.initials: PC
authors.lastname: Etches
authors.forename: R
authors.initials: R
authors.lastname: Schulz
authors.forename: J A
authors.initials: JA
authors.lastname: Talbot
authors.forename: A J
authors.initials: AJ
authors.lastname: Graham
authors.forename: R J
authors.initials: RJ
authors.lastname: Pearson
authors.forename: P Y
authors.initials: PY
authors.lastname: Cheung
mesh_terms: D000280:Administration, Inhalation; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy / Q000503:physiopathology; D007231:Infant, Newborn; D009569:Nitric Oxide / Q000037:antagonists & inhibitors* / Q000494:pharmacology / Q000627:therapeutic use*; D011897:Random Allocation; D012772:Shock, Septic / Q000188:drug therapy* / Q000382:microbiology; D013290:Streptococcal Infections / Q000188:drug therapy*; D013292:Streptococcus agalactiae; D013552:Swine; D013997:Time Factors
chemical_list: D009569:Nitric Oxide