Positive inotropic effect of coenzyme Q_{10},
omega-3 fatty acids and propionyl-L-carnitine on papillary muscle
force-frequency responses of BIO TO-2 cardiomyopathic Syrian hamsters
Issue title: The Fifth Conference of the International CoQ10
Association, Kobe 2007 – 50th anniversary of CoQ10 discovery
Affiliations: Dipartimento di Scienze Applicate ai Biosistemi,
Sezione di Fisiologia e Nutrizione Umana, Università di Cagliari, Cagliari,
Italy | Istituto di Biochimica, Università Politecnica
delle Marche, Ancona, Italy | Dipartimento di Citomorfologia, Sezione di Anatomia
Patologica, Università di Cagliari, Cagliari, 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.: + 39 070 675 8980; Fax: + 39 070 675 8917; E-mail:
mancinel@unica.it
Abstract: The inability of heart muscle to generate ventricular pressure to
adequately propel blood through the cardiovascular system is a primary defect
associated with congestive heart failure (CHF). Force-frequency relationship
(FFR) is one of the main cardiac defects associated with congestive heart
failure. Thus FFR is a convenient methodological tool for evaluating the
severity of muscle contractile dysfunction and the effectiveness of therapeutic
agents. Papillary muscle isolated from BIO TO-2 cardiomyopathic Syrian hamsters
(CMSHs), show a depressed FFR and represents an animal model of human
idiopathic dilated cardiomyopathy. In the present study we investigated the
effect of CoQ_{10}, omega-3 fatty acids,
propionyl-L-carnitine (PLC) and a combination of these 3 agents (formulation
HS12607) on FFR in 8 month old BIO TO-2 CMSHs. Papillary muscles isolated from
the anesthetized animals were placed in an incubation bath and attached to an
isometric force transducer. A digital computer with an analog/digital interface
allowed control of both muscle developed force and electrical stimulus
parameters. Force-frequency response was evaluated, at L_{max},
with increasing frequencies: 0.06, 0.12, 0.25, 0.5, 1, 2 and 4
Hz. HS12607-treatment produced a positive inotropic effect resulting in a
significant enhancement (p < 0.05) of the peak force at the
highest frequencies (1–4 Hz). In the range of frequency of 1–4 Hz also
CoQ_{10} and omega-3 significantly (p <
0.05) attenuated the fractional decline in developed force. The significant
improvement (p < 0.05) of the timing parameter peak rate of
tension rise (+ T') and peak rate of tension fall
(−T') indicating a faster rate of muscle contraction and
relaxation respectively, found in CoQ_{10}, omega-3 and
PLC-treated CMSHs, may be due to the positive effects of these substances on
sarcoplasmic reticulum functions. These findings suggest that naturally
occurring CoQ_{10}, omega-3 and PLC, particularly when
administered together in a coformulation, might be a valid adjuvant to
conventional therapy in dilated cardiomyopathy especially when considering that
they are natural substances, devoid of side effects.
