title: Impact of cardiac support device combined with slow-release prostacyclin agonist in a canine ischemic cardiomyopathy model.
abstract: BACKGROUND
  The cardiac support device supports the heart and mechanically reduces left ventricular (LV) diastolic wall stress. Although it has been shown to halt LV remodeling in dilated cardiomyopathy, its therapeutic efficacy is limited by its lack of biological effects. In contrast, the slow-release synthetic prostacyclin agonist ONO-1301 enhances reversal of LV remodeling through biological mechanisms such as angiogenesis and attenuation of fibrosis. We therefore hypothesized that ONO-1301 plus a cardiac support device might be beneficial for the treatment of ischemic cardiomyopathy.
  
  
  METHODS
  Twenty-four dogs with induced anterior wall infarction were assigned randomly to 1 of 4 groups at 1 week postinfarction as follows: cardiac support device alone, cardiac support device plus ONO-1301 (hybrid therapy), ONO-1301 alone, or sham control.
  
  
  RESULTS
  At 8 weeks post-infarction, LV wall stress was reduced significantly in the hybrid therapy group compared with the other groups. Myocardial blood flow, measured by positron emission tomography, and vascular density were significantly higher in the hybrid therapy group compared with the cardiac support device alone and sham groups. The hybrid therapy group also showed the least interstitial fibrosis, the greatest recovery of LV systolic and diastolic functions, assessed by multidetector computed tomography and cardiac catheterization, and the lowest plasma N-terminal pro-B-type natriuretic peptide levels (P < .05).
  
  
  CONCLUSIONS
  The combination of a cardiac support device and the prostacyclin agonist ONO-1301 elicited a greater reversal of LV remodeling than either treatment alone, suggesting the potential of this hybrid therapy for the clinical treatment of ischemia-induced heart failure.
authors.affiliation: Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Kubota
authors.affiliation: Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Miyagawa
authors.affiliation: Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Satsuki
authors.initials: S
authors.lastname: Fukushima
authors.affiliation: Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Atsuhiro
authors.initials: A
authors.lastname: Saito
authors.affiliation: Department of Molecular Imaging in Medicine, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Watabe
authors.affiliation: Department of Biostatistics, Hyogo College of Medicine, Hyogo, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Daimon
authors.affiliation: Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Sakai
authors.affiliation: Department of Cardiovascular Surgery, Kanazawa Medical University, Ishikawa, Japan.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Akita
authors.affiliation: Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Osaka, Japan. Electronic address: sawa-p@surg1.med.osaka-u.ac.jp.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Sawa
mesh_terms: D000818:Animals; D056988:Anterior Wall Myocardial Infarction / Q000150:complications*; D015415:Biomarkers / Q000097:blood; D009202:Cardiomyopathies / Q000097:blood / Q000175:diagnosis / Q000209:etiology / Q000503:physiopathology / Q000628:therapy*; D002317:Cardiovascular Agents / Q000494:pharmacology*; D002626:Chemistry, Pharmaceutical; D003131:Combined Modality Therapy; D003326:Coronary Circulation / Q000187:drug effects; D003692:Delayed-Action Preparations; D004195:Disease Models, Animal; D004285:Dogs; D005355:Fibrosis; D006352:Heart Ventricles / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D006353:Heart-Assist Devices; D020097:Natriuretic Peptide, Brain / Q000097:blood; D010446:Peptide Fragments / Q000097:blood; D044062:Prostaglandins I / Q000819:agonists* / Q000378:metabolism; D011474:Prosthesis Design; D011725:Pyridines / Q000494:pharmacology*; D020127:Recovery of Function; D013997:Time Factors; D016277:Ventricular Function, Left / Q000187:drug effects; D020257:Ventricular Remodeling / Q000187:drug effects
chemical_list: D015415:Biomarkers; D002317:Cardiovascular Agents; D003692:Delayed-Action Preparations; D010446:Peptide Fragments; D044062:Prostaglandins I; D011725:Pyridines; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain; C105488:ONO 1301