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.

Effects of n-3 Polyunsaturated Fatty Acids on Left Ventricular Function and Functional Capacity in Patients With Dilated Cardiomyopathy

“…In intact rats, chronic n-3 PUFA supplementation after aortic banding attenuated the increase in LV end-diastolic and end-systolic volumes, the decline of the velocity of circumferential shortening, and the reduction of LVEF, also preventing the switch in myosin heavy chain isoform from alpha to beta (6). Furthermore, in cardiomyopathic hamsters, n-3 PUFA administration led to a significant improvement in the peak rate of tension rise and peak rate of tension fall, which indicated a faster rate of muscle contraction and relaxation, respectively (15). These effects are likely related to the prevention of Ca 2ϩ overload and to the decrease of sarcoplasmatic reticulum Ca 2ϩ content (16).…”

Pharmacological effects and clinical applications of propionyl-L-carnitine

“…showed that the same concentrations of PLC did not exert any effect when PLC was delivered directly into the perfusate, but chronic intraperitoneal administration of PLC led to positive inotropy. Chronic administration of PLC also produced positive inotropy in the hearts of diabetic rats with experimentally induced cardiomyopathy, 42 in an in vivo animal model of anesthetized dogs, 43 and in a model of hereditary dilated cardiomyopathy 44,45 …”

Omega-3 fatty acids and heart failure

“…In older adults enrolled in the Cardiovascular Health Study, fi sh intake was associated with better cardiac function shown by incremental stroke volume through an improvement of early, and possibly late, diastolic fi lling [44•], confi rming in humans the fi ndings previously observed in nonhuman primates [45]. There is experimental evidence for a positive inotropic effect of n-3 PUFA due to a faster rate of cardiac muscle contraction and relaxation [46]. EPA and DHA have also been reported to prevent switching of the myosin heavy chain isoform from α to β, which is a marker of HF and left ventricular hypertrophy [43].…”