Effect of a novel thromboxane A2 inhibitor on right ventricular-arterial coupling in endotoxic shock.
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.
Lambermont
Bernard
B
Hemodynamics Research Laboratory (HemoLiege), Liege University, Belgium. b.lambermont@chu.ulg.ac.be
Kolh
Philippe
P
Ghuysen
Alexandre
A
Segers
Patrick
P
Dogné
Jean-Michel
JM
Tchana-Sato
Vincent
V
Morimont
Philippe
P
Benoit
Patricia
P
Gérard
Paul
P
Masereel
Bernard
B
D'Orio
Vincent
V
D000818:Animals; D002404:Catheterization; D004195:Disease Models, Animal; D004731:Endotoxins / Q000494:pharmacology; D005260:Female; D006352:Heart Ventricles / Q000378:metabolism*; D008297:Male; D009206:Myocardium / Q000473:pathology; D010100:Oxygen / Q000378:metabolism; D010196:Pancreatic Elastase / Q000378:metabolism; D010919:Placebos; D011312:Pressure; D011652:Pulmonary Circulation / Q000187:drug effects; D012772:Shock, Septic / Q000188:drug therapy* / Q000473:pathology*; D013552:Swine; D013599:Systole; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013997:Time Factors
D004731:Endotoxins; D010919:Placebos; D013928:Thromboxane A2; D010196:Pancreatic Elastase; D010100:Oxygen