title: Positive inotropic effect of coenzyme Q10, omega-3 fatty acids and propionyl-L-carnitine on papillary muscle force-frequency responses of BIO TO-2 cardiomyopathic Syrian hamsters.
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 CoQ10, 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 Lmax, 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 CoQ10 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 CoQ10, 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 CoQ10, 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.
authors.affiliation: Dipartimento di Scienze Applicate ai Biosistemi, Sezione di Fisiologia e Nutrizione Umana, Università di Cagliari, Cagliari, Italy.
authors.forename: Romina
authors.initials: R
authors.lastname: Vargiu
authors.forename: Gian Paolo
authors.initials: GP
authors.lastname: Littarru
authors.forename: Gavino
authors.initials: G
authors.lastname: Faa
authors.forename: Rino
authors.initials: R
authors.lastname: Mancinelli
mesh_terms: D000818:Animals; D009202:Cardiomyopathies / Q000188:drug therapy / Q000503:physiopathology; D002311:Cardiomyopathy, Dilated / Q000188:drug therapy / Q000503:physiopathology; D002331:Carnitine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006224:Cricetinae; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology*; D008297:Male; D008647:Mesocricetus; D023421:Models, Animal; D009200:Myocardial Contraction / Q000187:drug effects* / Q000502:physiology; D010210:Papillary Muscles / Q000187:drug effects* / Q000502:physiology; D013268:Stimulation, Chemical; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D015525:Fatty Acids, Omega-3; D014451:Ubiquinone; C003223:propionylcarnitine; C024989:coenzyme Q10; D002331:Carnitine