A metabolic approach to the treatment of dilated cardiomyopathy in BIO T0-2 cardiomyopathic Syrian hamsters.
Mechanisms underlying dilated cardiomyopathy (DCM) are poorly understood and effective therapy is still unavailable. The aim of this study was to examine the heart ultrastructure and dynamic of BIO T0-2 cardiomyopathic hamsters, an animal model of DCM, and to study in these animals, the effects of a co-formulation (HS12607) of propionyl-L-carnitine, coenzyme Q(10) and omega-3 fatty acids on cardiac mechanical parameters. Sarcomere length, Frank-Starling mechanism and force-frequency relations were studied on isolated ventricular papillary muscle from age-matched BIO F1B normal Syrian hamsters, BIO T0-2 control and BIO T0-2 HS12607-treated cardiomyopathic Syrian hamsters. At the optimum length to maximum active force, electron microscopy of left ventricular papillary muscle revealed that seven out of ten muscles studied showed shorter sarcomeres (1.20 +/- 0.29 microm), and the remaining three showed longer sarcomeres (2.80 +/- 0.13 microm), compared to those of normal hamsters (2.05 +/- 0.06 microm, n = 10). Severe alterations of the Frank-Starling mechanism, force-frequency relations and derivative parameters of contractile waves were also observed in vitro in the BIO T0-2 control hamsters. Long-term (8 weeks) treatment with HS12607 prevented alterations in sarcomere length in the BIO T0-2 cardiomyopathic hamsters; the Frank-Starling mechanism and force-frequency relations were also significantly (P < 0.05) improved in these hamsters. Therefore results of the present study strongly suggest the need for clinical studies on metabolic therapeutic intervention in the effort to stop the progression of dilated cardiomyopathy.
Mancinelli
Rino
R
Dipartimento di Scienze Applicate ai Biosistemi, Sezione di Fisiologia e Nutrizione Umana, Università di Cagliari, Italy. mancinel@unica.it
Vargiu
Romina
R
Cappai
Antonello
A
Floris
Giuseppe
G
Fraschini
Matteo
M
Faa
Gavino
G
D000818:Animals; D002311:Cardiomyopathy, Dilated / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D002331:Carnitine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006224:Cricetinae; D004195:Disease Models, Animal; D004558:Electric Stimulation; D015525:Fatty Acids, Omega-3 / Q000627:therapeutic use*; D008297:Male; D008647:Mesocricetus; D009200:Myocardial Contraction / Q000187:drug effects; D010210:Papillary Muscles / Q000187:drug effects; D012518:Sarcomeres / Q000187:drug effects / Q000648:ultrastructure; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000627:therapeutic use
D015525:Fatty Acids, Omega-3; C513905:HS12607; D014451:Ubiquinone; D002331:Carnitine