Effect of a novel thromboxane A2 inhibitor on right ventricular-arterial coupling in endotoxic shock

Bernard Lambermont, Philippe Kolh, Alexandre Ghuysen, Patrick Segers, Jean-Michel Dogné, Vincent Tchana-Sato, Philippe Morimont, Patricia Benoit, Paul Gérard, Bernard Masereel, Vincent D'Orio

Research output: Contribution to journalArticlepeer-review

Abstract

We investigated the effects of a dual thromboxane (TX)A2 synthase inhibitor and TXA2 receptor antagonist (BM-573) on right ventricular-arterial coupling in a porcine model of endotoxic shock. Thirty minutes before the onset of 0.5 mg/kg endotoxin infusion, six pigs (Endo group) received an infusion with a placebo solution, and six other pigs (Anta group) with BM-573. Right ventricular pressure-volume loops were obtained by the conductance catheter technique. The slope (Ees) of the end-systolic pressure-volume relationship and its volume intercept at 25 mmHg were calculated as measures of right ventricular systolic function. RV afterload was quantified by pulmonary arterial elastance (Ea), and Ees/Ea ratio represented right ventricular-arterial coupling. Mechanical efficiency was defined as the ratio of stroke work and pressure-volume area. In this model of endotoxic shock, BM-573 blunted the early phase of pulmonary hypertension, improved arterial oxygenation, and prevented a decrease in right ventricular myocardial efficiency and right ventricular dilatation. However, the drug could not prevent the loss of homeometric regulation and alterations in right ventricular-arterial coupling. In conclusion, dual TXA2 synthase inhibitor and receptor antagonists such as BM-573 have potential therapeutic applications, improving right ventricular efficiency and arterial oxygenation in endotoxic shock.
Original languageEnglish
Pages (from-to)45-51
Number of pages7
JournalShock (Augusta, Ga.)
Volume21
Issue number1
DOIs
Publication statusPublished - Jan 2004

Keywords

  • Animals
  • Catheterization
  • Disease Models, Animal
  • Endotoxins
  • Female
  • Heart Ventricles
  • Male
  • Myocardium
  • Oxygen
  • Pancreatic Elastase
  • Placebos
  • Pressure
  • Pulmonary Circulation
  • Shock, Septic
  • Swine
  • Systole
  • Thromboxane A2
  • Time Factors

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