title: Preservation of diastolic function in monocrotaline-induced right ventricular hypertrophy in rats.
abstract: During ischemic heart diseases and when heart failure progresses depletion of myocardial energy stores occurs. D-Ribose (R) has been shown to improve cardiac function and energy status after ischemia. Folic acid (FA) is an essential cofactor in the formation of adenine nucleotides. Therefore, we assessed whether chronic R-FA administration during the development of hypertrophy resulted in an improved cardiac function and energy status. In Wistar rats (n = 40) compensatory right ventricular (RV) hypertrophy was induced by monocrotaline (30 mg/kg; MCT), whereas saline served as control. Both groups received a daily oral dose of either 150 mg.kg(-1).day(-1) dextrose (placebo) or R-FA (150 and 40 mg.kg(-1).day(-1), respectively). In Langendorff-perfused hearts, RV and left ventricular (LV) pressure development and collagen content as well as total RV adenine nucleotides (TAN), creatine content, and RV and LV collagen content were determined. In the control group R-FA had no effect. In the MCT-placebo group, TAN and creatine content were reduced, RV and LV diastolic pressure-volume relations were steeper, RV systolic pressures were elevated, RV and LV collagen content was increased, and RV-LV diastolic interaction was altered compared with controls. In the MCT-R-FA group, TAN, RV and LV diastolic stiffness, RV and LV collagen content, and RV-LV diastolic interaction were normalized to the values in the control group while creatine content remained depressed and RV systolic function remained elevated. In conclusion, the depression of energy status in compensated hypertrophic myocardium observed was partly prevented by chronic R-FA administration and accompanied by a preservation of diastolic function and collagen deposition.
authors.affiliation: Department of Anesthesiology, Institute for Cardiovascular Research-Vrije University (ICaR-VU), Vrije University Medical Center (VUMC), Amsterdam, The Netherlands. r.lamberts@vumc.nl
authors.forename: Regis R
authors.initials: RR
authors.lastname: Lamberts
authors.forename: Eric
authors.initials: E
authors.lastname: Caldenhoven
authors.forename: Mirian
authors.initials: M
authors.lastname: Lansink
authors.forename: Gerrit
authors.initials: G
authors.lastname: Witte
authors.forename: Rob J
authors.initials: RJ
authors.lastname: Vaessen
authors.forename: John A
authors.initials: JA
authors.lastname: St Cyr
authors.forename: Ger J M
authors.initials: GJ
authors.lastname: Stienen
mesh_terms: D000227:Adenine Nucleotides / Q000378:metabolism; D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D003094:Collagen / Q000378:metabolism; D003401:Creatine / Q000378:metabolism; D019587:Dietary Supplements; D005492:Folic Acid / Q000494:pharmacology / Q000627:therapeutic use*; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism; D006710:Homocysteine / Q000097:blood; D017380:Hypertrophy, Right Ventricular / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology*; D008297:Male; D016686:Monocrotaline; D009200:Myocardial Contraction / Q000187:drug effects; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D016277:Ventricular Function, Left / Q000187:drug effects / Q000502:physiology; D016278:Ventricular Function, Right / Q000187:drug effects / Q000502:physiology*
chemical_list: D000227:Adenine Nucleotides; D006710:Homocysteine; D016686:Monocrotaline; D003094:Collagen; D005492:Folic Acid; D003401:Creatine