title: Riociguat reduces infarct size and post-infarct heart failure in mouse hearts: insights from MRI/PET imaging.
abstract: OBJECTIVE
  Stimulation of the nitric oxide (NO)--soluble guanylate (sGC)--protein kinase G (PKG) pathway confers protection against acute ischaemia/reperfusion injury, but more chronic effects in reducing post-myocardial infarction (MI) heart failure are less defined. The aim of this study was to not only determine whether the sGC stimulator riociguat reduces infarct size but also whether it protects against the development of post-MI heart failure.
  
  
  RESULTS
  Mice were subjected to 30 min ischaemia via ligation of the left main coronary artery to induce MI and either placebo or riociguat (1.2 µmol/l) were given as a bolus 5 min before and 5 min after onset of reperfusion. After 24 hours, both, late gadolinium-enhanced magnetic resonance imaging (LGE-MRI) and (18)F-FDG-positron emission tomography (PET) were performed to determine infarct size. In the riociguat-treated mice, the resulting infarct size was smaller (8.5 ± 2.5% of total LV mass vs. 21.8% ± 1.7%. in controls, p = 0.005) and LV systolic function analysed by MRI was better preserved (60.1% ± 3.4% of preischaemic vs. 44.2% ± 3.1% in controls, p = 0.005). After 28 days, LV systolic function by echocardiography treated group was still better preserved (63.5% ± 3.2% vs. 48.2% ± 2.2% in control, p = 0.004).
  
  
  CONCLUSIONS
  Taken together, mice treated acutely at the onset of reperfusion with the sGC stimulator riociguat have smaller infarct size and better long-term preservation of LV systolic function. These findings suggest that sGC stimulation during reperfusion therapy may be a powerful therapeutic treatment strategy for preventing post-MI heart failure.
authors.affiliation: Department of Medicine, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Carmen
authors.initials: C
authors.lastname: Methner
authors.affiliation: Wolfson Brain Imaging Centre, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Guido
authors.initials: G
authors.lastname: Buonincontri
authors.affiliation: Department of Medicine, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Chou-Hui
authors.initials: CH
authors.lastname: Hu
authors.affiliation: Department of Medicine, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Ana
authors.initials: A
authors.lastname: Vujic
authors.affiliation: Bayer HealthCare, Wuppertal, Germany.
authors.forename: Axel
authors.initials: A
authors.lastname: Kretschmer
authors.affiliation: Wolfson Brain Imaging Centre, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Stephen
authors.initials: S
authors.lastname: Sawiak
authors.affiliation: Wolfson Brain Imaging Centre, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Adrian
authors.initials: A
authors.lastname: Carpenter
authors.affiliation: Bayer HealthCare, Wuppertal, Germany.
authors.forename: Johannes-Peter
authors.initials: JP
authors.lastname: Stasch
authors.affiliation: Department of Medicine, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Thomas
authors.initials: T
authors.lastname: Krieg
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000032:analysis; D004452:Echocardiography; D006162:Guanylate Cyclase / Q000378:metabolism*; D006333:Heart Failure / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D006439:Hemodynamics / Q000187:drug effects; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D049268:Positron-Emission Tomography; D011720:Pyrazoles / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use*; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D000071756:Soluble Guanylyl Cyclase
chemical_list: D015415:Biomarkers; D011720:Pyrazoles; D011743:Pyrimidines; D018160:Receptors, Cytoplasmic and Nuclear; D006162:Guanylate Cyclase; D000071756:Soluble Guanylyl Cyclase; C542595:riociguat