title: Effects of antiplatelet agents on pulmonary haemodynamic response to fMLP in endotoxin primed rats.
abstract: BACKGROUND
  The interaction between neutrophils and platelets may be important in the modulation of pulmonary haemodynamics under systemic inflammatory conditions. A study was undertaken to examine whether antiplatelet agents inhibit platelet-neutrophil adherence and ameliorate the pulmonary haemodynamic response to fMLP by inhibiting thromboxane release in endotoxin primed lungs. fMLP stimulates neutrophils but not platelets; however, thromboxane synthesis in neutrophils is very low.
  
  
  METHODS
  Rats were pretreated with either cilostazol (300 mg/kg) or aspirin (50 mg/kg) before endotoxin priming (5 mg/kg). Platelets in the lung were identified by fluorescent immunohistochemistry. Platelet-neutrophil adherence was analysed by flow cytometry of the lung vascular flush. The effect of fMLP (10(-6) M) on thromboxane release, lung weight (an indicator of pulmonary vasoconstriction), and lung filtration coefficient was determined in an isolated lung system perfused at a constant pressure difference.
  
  
  RESULTS
  Endotoxin induced platelet accumulation and platelet-neutrophil adherence in the lung capillary were completely inhibited by cilostazol and aspirin while neutrophil recruitment was not affected. The fMLP challenge caused a significant increase in thromboxane B2 levels in endotoxin primed lungs. The fMLP induced decrease in lung weight was enhanced by endotoxin priming (from -4.9 to -63.9 mg, 95% CI of mean difference -99.5 to -10.5 mg, p<0.05). The fMLP induced increase in the lung filtration coefficient was also enhanced by endotoxin priming (from 0.63 to 2.40 mg/min/cm H2O/g, 95% CI of mean difference 1.17 to 2.37 mg/min/cm H2O/g, p<0.05). Treatment with cilostazol and aspirin completely inhibited the enhanced pulmonary haemodynamic response to fMLP.
  
  
  CONCLUSIONS
  The neutrophil-platelet interaction is of critical importance in the modulation of pulmonary haemodynamics via thromboxane.
authors.affiliation: Department of Thoracic Surgery, Institute of Development, Aging and Cancer, Tohoku University, 4-1 Seiryo-machi, Aoba-ku, Sendai, Japan 980-8575.
authors.forename: C
authors.initials: C
authors.lastname: Song
authors.forename: S
authors.initials: S
authors.lastname: Suzuki
authors.forename: H
authors.initials: H
authors.lastname: Kubo
authors.forename: M
authors.initials: M
authors.lastname: Chida
authors.forename: Y
authors.initials: Y
authors.lastname: Hoshikawa
authors.forename: T
authors.initials: T
authors.lastname: Tabata
authors.forename: T
authors.initials: T
authors.lastname: Kondo
mesh_terms: D000818:Animals; D001241:Aspirin / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects; D002448:Cell Adhesion / Q000187:drug effects; D000077407:Cilostazol; D004731:Endotoxins / Q000494:pharmacology; D005434:Flow Cytometry; D006439:Hemodynamics / Q000187:drug effects; D008168:Lung / Q000502:physiology*; D008297:Male; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology*; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013777:Tetrazoles / Q000494:pharmacology*; D013928:Thromboxane A2 / Q000378:metabolism
chemical_list: D004731:Endotoxins; D010975:Platelet Aggregation Inhibitors; D013777:Tetrazoles; D013928:Thromboxane A2; D009240:N-Formylmethionine Leucyl-Phenylalanine; D000077407:Cilostazol; D001241:Aspirin