title: Myocardial Response to Milrinone in Single Right Ventricle Heart Disease.
abstract: Empiric treatment with milrinone, a phosphodiesterase (PDE) 3 inhibitor, has become increasingly common in patients with single ventricle heart disease of right ventricular (RV) morphology (SRV); our objective was to characterize the myocardial response to PDE3 inhibition (PDE3i) in the pediatric population with SRV.
  
  
  
  Cyclic adenosine monophosphate levels, PDE activity, and phosphorylated phospholamban (PLN) were determined in explanted human ventricular myocardium from nonfailing pediatric donors (n = 10) and pediatric patients transplanted secondary to SRV. Subjects with SRV were further classified by PDE3i treatment (n = 13 with PDE3i and n = 12 without PDE3i).
  
  
  
  In comparison with nonfailing RV myocardium (n = 8), cyclic adenosine monophosphate levels are lower in patients with SRV treated with PDE3i (n = 12, P = .021). Chronic PDE3i does not alter total PDE or PDE3 activity in SRV myocardium. Compared with nonfailing RV myocardium, SRV myocardium (both with and without PDE3i) demonstrates equivalent phosphorylated PLN at the protein kinase A phosphorylation site.
  
  
  
  As evidenced by preserved phosphorylated PLN, the molecular adaptation associated with SRV differs significantly from that demonstrated in pediatric heart failure because of dilated cardiomyopathy. These alterations support a pathophysiologically distinct mechanism of heart failure in pediatric patients with SRV, which has direct implications regarding the presumed response to PDE3i treatment in this population.
authors.affiliation: Division of Cardiology, Department of Pediatrics, University of Colorado School of Medicine, Children's Hospital Colorado, Aurora, CO.
authors.forename: Stephanie J
authors.initials: SJ
authors.lastname: Nakano
authors.affiliation: Division of Cardiology, Department of Medicine, University of Colorado Denver, Aurora, CO.
authors.forename: Penny
authors.initials: P
authors.lastname: Nelson
authors.affiliation: Division of Cardiology, Department of Medicine, University of Colorado Denver, Aurora, CO.
authors.forename: Carmen C
authors.initials: CC
authors.lastname: Sucharov
authors.affiliation: Division of Cardiology, Department of Pediatrics, University of Colorado School of Medicine, Children's Hospital Colorado, Aurora, CO. Electronic address: shelley.miyamoto@childrenscolorado.org.
authors.forename: Shelley D
authors.initials: SD
authors.lastname: Miyamoto
mesh_terms: D000249:Adenosine Monophosphate / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002311:Cardiomyopathy, Dilated / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D005260:Female; D016027:Heart Transplantation; D006352:Heart Ventricles / Q000002:abnormalities*; D006801:Humans; D007223:Infant; D008297:Male; D020105:Milrinone / Q000627:therapeutic use*; D009206:Myocardium / Q000378:metabolism*; D058987:Phosphodiesterase 3 Inhibitors / Q000627:therapeutic use*; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D000099211:Phospholamban
chemical_list: D000249:Adenosine Monophosphate; D002135:Calcium-Binding Proteins; D020105:Milrinone; D058987:Phosphodiesterase 3 Inhibitors; D010727:Phosphoric Diester Hydrolases; D000099211:Phospholamban
keywords: cyclic adenosine monophosphate; pediatric heart failure; phosphodiesterase; phospholamban