Affiliations: Dipartimento di Scienze Applicate ai Biosistemi,
Sezione di Fisiologia e Nutrizione Umana, Università di Cagliari, Via
Porcell 4, I-09124 Cagliari, Italy | Dipartimento di Citomorfologia, Sezione di Anatomia
Patologica, Università di Cagliari, Via Ospedale 60, I-09124 Cagliari,
Italy | Dipartimento di Scienze Mediche Internistiche,
Università di Cagliari, S. S. 554 Policlinico Universitario, I-09044
Monserrato, Italy
Note: [] Address for correspondence: Professor Rino Mancinelli,
Dipartimento di Scienze Applicate ai Biosistemi, Sezione di Fisiologia e
Nutrizione Umana, Università di Cagliari, Via Porcell 4, I-09124
Cagliari, Italy. Tel.: +39 070 6758980; Fax: +39 070 6758917; E-mail:
mancinel@unica.it
Abstract: 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
± 0.29μm), and the remaining three showed longer sarcomeres (2.80
± 0.13μm), compared to those of normal hamsters (2.05±
0.06μm, 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.
