Inhibition of prostaglandin synthesis during polystyrene microsphere-induced pulmonary embolism in the rat

Alan E. Jones, John A. Watts, Jacob P. Debelak, Lisa R. Thornton, John G. Younger, Jeffrey A. Kline

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

Our objective was to test the effect of inhibition of thromboxane synthase versus inhibition of cyclooxygenase (COX)-1/2 on pulmonary gas exchange and heart function during simulated pulmonary embolism (PE) in the rat. PE was induced in rats via intrajugular injection of polystyrene microspheres (25 μm). Rats were randomized to one of three posttreatments: 1) placebo (saline), 2) thromboxane synthase inhibition (furegrelate sodium), or 3) COX-1/2 inhibition (ketorolac tromethamine). Control rats received no PE. Compared with controls, placebo rats had increased thromboxane B2 (TxB2) in bronchoalveolar lavage fluid and increased urinary dinor TxB2. Furegrelate and ketorolac treatments reduced TxB2 and dinor TxB2 to control levels or lower. Both treatments significantly decreased the alveolar dead space fraction, but neither treatment altered arterial oxygenation compared with placebo. Ketorolac increased in vivo mean arterial pressure and ex vivo left ventricular pressure (LVP) and right ventricular pressure (RVP). Furegrelate improved RVP but not LVP. Experimental PE increased lung and systemic production of TxB2. Inhibition at the COX-1/2 enzyme was equally as effective as inhibition of thromboxane synthase at reducing alveolar dead space and improving heart function after PE.

Original languageEnglish (US)
Pages (from-to)L1072-L1081
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume284
Issue number6 28-6
StatePublished - Jun 1 2003

Fingerprint

Thromboxane B2
Polystyrenes
Pulmonary Embolism
Microspheres
Prostaglandins
Ventricular Pressure
Cyclooxygenase 1
Thromboxanes
Cyclooxygenase 2
Ketorolac
Placebos
Ketorolac Tromethamine
Pulmonary Gas Exchange
Bronchoalveolar Lavage Fluid
Arterial Pressure
Therapeutics
Sodium
Lung
Injections
Enzymes

Keywords

  • Animal model
  • Cyclooxygenase
  • Heart failure
  • Ketorolac
  • Langendorff
  • Leukotriene
  • Thromboembolism/treatment
  • Thromboxane

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

Cite this

Inhibition of prostaglandin synthesis during polystyrene microsphere-induced pulmonary embolism in the rat. / Jones, Alan E.; Watts, John A.; Debelak, Jacob P.; Thornton, Lisa R.; Younger, John G.; Kline, Jeffrey A.

In: American Journal of Physiology - Lung Cellular and Molecular Physiology, Vol. 284, No. 6 28-6, 01.06.2003, p. L1072-L1081.

Research output: Contribution to journalArticle

Jones, Alan E. ; Watts, John A. ; Debelak, Jacob P. ; Thornton, Lisa R. ; Younger, John G. ; Kline, Jeffrey A. / Inhibition of prostaglandin synthesis during polystyrene microsphere-induced pulmonary embolism in the rat. In: American Journal of Physiology - Lung Cellular and Molecular Physiology. 2003 ; Vol. 284, No. 6 28-6. pp. L1072-L1081.
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