A soluble guanylate cyclase stimulator, BAY 41-8543, preserves right ventricular function in experimental pulmonary embolism

John A. Watts, Michael A. Gellar, Mary Beth K. Fulkerson, Jeffrey A. Kline

Research output: Contribution to journalArticle

6 Scopus citations

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), +d. P/d. t (1192 ± 93 mmHg/s vs. 444 ± 64) and -d. P/d. t (-576 ± 60 mmHg/s vs. -278 ± 40). BAY 41-8543 significantly improved all three indices of RV heart function (PSP 35 ± 3.5, +d. P/d. t 1129 ± 100, -d. P/d. t -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.

Original languageEnglish (US)
Pages (from-to)205-211
Number of pages7
JournalPulmonary Pharmacology and Therapeutics
Volume26
Issue number2
DOIs
StatePublished - Apr 1 2013

Keywords

  • BAY 41-8543
  • Pulmonary embolism
  • Pulmonary heart disease
  • Pulmonary vascular resistance
  • Right ventricle
  • Soluble guanylate cyclase stimulator

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Pharmacology (medical)
  • Biochemistry, medical

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