Thromboxane and pulmonary morphometry in the development of the pulmonary hypertensive response to group B streptococcus

Academic Article

Abstract

  • Objective: To clarify the mechanism of the development of a severe pulmonary hypertensive response to group B streptococcus. Design: Prospective, randomized controlled trial. Subjects: Twelve chronically instrumented and six age-matched uninstrumented newborn piglets. Interventions: Six animals received eight injections of group B streptococcus over an 11-day period (control group). Six additional animals (pretreatment group) were given 3 mg/kg of dazmegrel, a thromboxane synthase blocking agent, before each dose of group B streptococcus to prevent the pulmonary hypertensive response and to control for any secondary arterial remodeling. Measurements and Main Results: Hemodynamic measurements, pulmonary arterial morphometry, and thromboxane concentrations were examined in the instrumented animals. Lungs from the uninstrumented piglets were examined to determine morphometric norms for this population. The animals given only group B streptococcus developed a significant pulmonary hypertensive response after five daily doses (+6.8 ± 2.0 [SEM] mm Hg, p < .05) which became pronounced after eight doses (+13.2 ± 1.0 mm Hg). Pulmonary hypertension was not observed in the pretreatment group when dazmegrel was given; however, on the final day in this group, dazmegrel was withheld before group B streptococcus dosing and a significant pulmonary hypertensive response was observed (+20 ± 1.6 mm Hg). The medial thickness of pulmonary arteries was not different between the two groups nor when compared with that of six normal, uninstrumented animals. Plasma thromboxane B2 concentrations were determined from blood samples taken before and after group B streptococcus infusion at the first, seventh and eighth (final) dosing. Thromboxane concentrations increased significantly on days 7 and 8 in the control group (578 ± 312 to 752 ± 372 pg/mL, 638 ± 201 to 1462 ± 295 pg/mL, respectively) and on day 8 in the pretreatment group (545 ± 160 to 705 ± 187 pg/mL). Conclusions: We conclude that the development of potentiated pulmonary hypertension is not due to pulmonary arterial remodeling, but is associated with increased thromboxane production.
  • Digital Object Identifier (doi)

    Author List

  • Barefield ES; Hicks TP; Philips JB
  • Start Page

  • 506
  • End Page

  • 514
  • Volume

  • 22
  • Issue

  • 3