Effects of antiplatelet agents on pulmonary haemodynamic response to fMLP in endotoxin primed rats

C. Song, S. Suzuki, H. Kubo, M. Chida, Yasushi Hoshikawa, T. Tabata, T. Kondo

Research output: Contribution to journalArticle

10 Citations (Scopus)

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 82 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. Conclusion: The neutrophil-platefet interaction is of critical importance in the modulation of pulmonary haemodynamics via thromboxane.

Original languageEnglish
Pages (from-to)39-44
Number of pages6
JournalThorax
Volume59
Issue number1
DOIs
Publication statusPublished - 01-01-2004

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Platelet Aggregation Inhibitors
Endotoxins
Hemodynamics
Lung
Thromboxanes
Neutrophils
Blood Platelets
Aspirin
Weights and Measures
Neutrophil Infiltration
Vasoconstriction
Blood Vessels

All Science Journal Classification (ASJC) codes

  • Pulmonary and Respiratory Medicine

Cite this

Song, C. ; Suzuki, S. ; Kubo, H. ; Chida, M. ; Hoshikawa, Yasushi ; Tabata, T. ; Kondo, T. / Effects of antiplatelet agents on pulmonary haemodynamic response to fMLP in endotoxin primed rats. In: Thorax. 2004 ; Vol. 59, No. 1. pp. 39-44.
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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 82 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. Conclusion: The neutrophil-platefet interaction is of critical importance in the modulation of pulmonary haemodynamics via thromboxane.",
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Effects of antiplatelet agents on pulmonary haemodynamic response to fMLP in endotoxin primed rats. / Song, C.; Suzuki, S.; Kubo, H.; Chida, M.; Hoshikawa, Yasushi; Tabata, T.; Kondo, T.

In: Thorax, Vol. 59, No. 1, 01.01.2004, p. 39-44.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Effects of antiplatelet agents on pulmonary haemodynamic response to fMLP in endotoxin primed rats

AU - Song, C.

AU - Suzuki, S.

AU - Kubo, H.

AU - Chida, M.

AU - Hoshikawa, Yasushi

AU - Tabata, T.

AU - Kondo, T.

PY - 2004/1/1

Y1 - 2004/1/1

N2 - 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 82 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. Conclusion: The neutrophil-platefet interaction is of critical importance in the modulation of pulmonary haemodynamics via thromboxane.

AB - 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 82 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. Conclusion: The neutrophil-platefet interaction is of critical importance in the modulation of pulmonary haemodynamics via thromboxane.

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