title: A soluble guanylate cyclase stimulator, BAY 41-8543, preserves right ventricular function in experimental pulmonary embolism.
abstract: Pulmonary embolism (PE) increases pulmonary vascular resistance, causing right ventricular (RV) dysfunction, and poor clinical outcome. Present studies test if the soluble guanylate cyclase stimulator BAY 41-8543 reduces pulmonary vascular resistance and protects RV function. Experimental PE was induced in anesthetized, male Sprague-Dawley rats by infusing 25 μm polystyrene microspheres (1.95 million/100 g body wt, right jugular vein) producing moderate PE. Pulmonary artery vascular resistance, estimated as RVPSP/CO, increased 3-fold after 5 h of PE. Treatment with BAY 41-8543 (50 μg/kg, I.V.; given at the time of PE induction) normalized this index by reducing RVPSP and markedly increasing CO, via preservation of heart rate and stroke volume. Ex vivo RV heart function showed minimal changes at 5 h of PE, but decreased significantly after 18 h of PE, including peak systolic pressure (PSP, Control 39 ± 1 mmHg vs. 19 ± 3 PE), +dP/dt (1192 ± 93 mmHg/s vs. 444 ± 64) and -dP/dt (-576 ± 60 mmHg/s vs. -278 ± 40). BAY 41-8543 significantly improved all three indices of RV heart function (PSP 35 ± 3.5, +dP/dt 1129 ± 100, -dP/dt -568 ± 87). Experimental PE produced increased PVR and RV dysfunction, which were ameliorated by treatment with BAY 41-8543. Thus, there is vasodilator reserve in this model of experimental PE that can be exploited to reduce the stress upon the heart and preserve RV contractile function.
authors.affiliation: Department of Emergency Medicine, Carolinas Medical Center, Charlotte, NC, USA. jwatts@carolinas.org
authors.forename: John A
authors.initials: JA
authors.lastname: Watts
authors.forename: Michael A
authors.initials: MA
authors.lastname: Gellar
authors.forename: Mary-Beth K
authors.initials: MB
authors.lastname: Fulkerson
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Kline
mesh_terms: D000818:Animals; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D009025:Morpholines / Q000627:therapeutic use*; D010996:Pleural Effusion / Q000188:drug therapy; D011655:Pulmonary Embolism / Q000188:drug therapy* / Q000503:physiopathology; D011743:Pyrimidines / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019210:Troponin I / Q000097:blood; D016278:Ventricular Function, Right / Q000187:drug effects*
chemical_list: C450679:BAY 41-8543; D009025:Morpholines; D011743:Pyrimidines; D019210:Troponin I