Abstract
Background: Pulmonary embolism (PE) increases pulmonary vascular resistance (PVR) and may cause right ventricular (RV) dysfunction, leading to poor clinical outcome. Our studies show BAY 41-8543 reduces PVR in experimental PE (Watts, J.A. et al., Crit Care Med 2011; 39:2700-2704), but effects upon RV function were previously unknown. Aims: The studies test if soluble guanylate cyclase stimulator (BAY 41-8543) treatment protects RV function in experimental PE. Methods: Experimental PE was induced in anesthetized, Sprague-Dawley rats by infusing 25µm polystyrene microspheres in the right jugular vein producing severe PE (2.6 million/100 gm body wt, 5 hrs) or moderate PE (2.0 million/100 gm, 18 hrs). PVR was estimated in-Vivo. Heart function was studied ex-Vivo using Langendorff technique. Results: Moderate PE produced a significant 3-fold increase in PVR, which was prevented by BAY 41-8543 (50 µg/kg, I.V.) treatment (Control 0.6 ± 0.04; PE 1.9 ± 0.2; PE + BAY 41-8543 0.7 ± 0.04 mmHg/ml/min). Moderate PE caused a significant decrease in RV peak systolic pressure (PSP, Control 39 ± 1 mmHg vs. 19 ± 3 PE), +dP/dt (1192 ± 93 mmHg/sec vs. 444 ± 64) and -dP/dt (-576 ± 60 mmHg/sec vs. 278 ± 40). BAY 41-8543 significantly improved all three indices of RV function (PSP 35 ± 3.5, +dP/dt 1128 ± 100, -dP/dt -568 ± 87). Severe PE caused significant RV dysfunction (PSP 26 ± 2, -dP/dt -369 ± 29) and BAY 41-8543 protected RV function (PSP 34 ± 2, -dP/dt -535 ± 41). Conclusions: Experimental PE increases PVR and produces RV dysfunction. Treatment of the animals with the soluble guanylate cyclase stimulator, BAY 41-8543, reduces PVR and improves RV function.
- © 2012 ERS
