Abstract | BACKGROUND: METHODS AND RESULTS: cAMP levels, PDE activity, and phospholamban phosphorylation (pPLB) were determined in explanted human left ventricular myocardium (pediatric n=41; adult n=88). Adults and children with IDC (not treated with PDE3i) had lower cAMP and pPLB compared with nonfailing controls. In contrast to their adult counterparts, pediatric IDC patients chronically treated with PDE3i had elevated cAMP (P=0.0403) and pPLB (P=0.0119). In addition, total PDE- and PDE3-specific activities were not altered in pediatric IDC patients on PDE3i, whereas adult IDC patients on PDE3i demonstrated higher total PDE-specific (74.6±13.8 pmol/mg per minute) and PDE3-specific (48.2±15.9 pmol/mg per minute) activities in comparison with those of nonfailing controls (59.5±14.4 and 35.5±12.8 pmol/mg per minute, respectively). CONCLUSIONS: Elevated cAMP and higher pPLB may contribute to sustained hemodynamic benefits in pediatric IDC patients treated with PDE3i. In contrast, higher total PDE and PDE3 activities in adult IDC patients treated with PDE3i may perpetuate lower myocardial cAMP and pPLB levels, limiting the potential benefits of PDE3i therapy.
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Authors | Stephanie J Nakano, Shelley D Miyamoto, Matthew Movsesian, Penny Nelson, Brian L Stauffer, Carmen C Sucharov |
Journal | Circulation. Heart failure
(Circ Heart Fail)
Vol. 8
Issue 1
Pg. 57-63
(Jan 2015)
ISSN: 1941-3297 [Electronic] United States |
PMID | 25278000
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
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Copyright | © 2014 American Heart Association, Inc. |
Chemical References |
- Phosphodiesterase 3 Inhibitors
- Phosphoric Diester Hydrolases
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Topics |
- Adolescent
- Adult
- Aged
- Blotting, Western
- Cardiomyopathy, Dilated
(drug therapy, enzymology, physiopathology)
- Child
- Child, Preschool
- Enzyme-Linked Immunosorbent Assay
- Female
- Humans
- Male
- Middle Aged
- Myocardial Contraction
(physiology)
- Phosphodiesterase 3 Inhibitors
(therapeutic use)
- Phosphoric Diester Hydrolases
(blood, drug effects)
- Prognosis
- Young Adult
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