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Enhancement of shortening velocity, power, and acto-myosin crossbridge (CB) kinetics following long-term treatment with propionyl-L-carnitine, coenzyme Q10, and omega-3 fatty acids in BIO TO-2 cardiomyopathic Syrian hamsters papillary muscle.

Impaired functions of myocardial muscle cells in human and animals, is a primary defect associated with idiopathic dilated cardiomyopathy (DCM). The pathophysiological mechanisms implicated in the DCM are yet to be clarified and an effective therapy is still not available. The BIO TO‐2 cardiomyopathic Syrian Hamsters (CMSHs) represent an animal model of idiopathic DCM. The aim of this study was to investigate the effect of long‐term treatment (2 months) with propionyl‐L‐carnitine (PLC), coenzyme Q10, omega‐3 fatty acids and a combination of these three agents (formulation HS12607) on mechanical properties and acto‐myosin crossbridges (CBs) kinetics of left ventricular (LV) papillary muscle from control and treated 10 month old BIO TO‐2 CMSHs. Isometric and isotonic contractile properties of isolated papillary muscle from control and treated CMSHs were investigated, and acto‐myosin CB number, force and kinetics were calculated using Huxleys equations. Mechanical parameter values were higher in treated than in control hamsters, particularly when substances were administered together in a coformulation (HS12607). Compared to control, HS12607‐treated papillary muscles showed a significant increase of maximum peak isometric tension (Po) (30.06 ± 4.91 vs. 19.74 ± 5.00 mN/mm2), maximum extent of muscle shortening (0.13 ± 0.03 vs. 0.07 ± 0.02 L/Lmax), maximum unloaded shortening velocity (1.18 ± 0.24 vs. 0.53 ± 0.13 L/Lmax s−1) and maximum peak of power output (5.52 ± 1.61 vs. 1.58 ± 0.83). The curvature of the hyperbolic force‐velocity relationships did not differ between control and treated hamsters. When compared to controls, acto‐myosin CB number increased in treated hamsters [(6.67 ± 1.91) 1010/mm2 vs. (3.55 ± 2.08) 1010/mm2], whereas the unitary force of single CB was similar in control and treated animals. The peak value of the rate constant for CB attachment (f1) and detachment (g2) was higher in treated animals when compared to control. (93.87 ± 25.82 vs.47.28 ± 10.88 s−1 and 214.40 ± 44.64 vs. 95.56 ± 23.49 s−1, respectively). In conclusion, the present study illustrates that supplementation with PLC, CoQ10 and omega‐3 fatty acids improved motor parameters, energetic, and CB kinetics of BIO TO‐2 CMSH papillary muscle indicating that these naturally occurring substances may be a valid adjuvant to conventional therapy in DCM.

Origin of motion in the human ureter: mechanics, energetics and kinetics of the myosin molecular motors

Background Ureteral peristalsis is the result of coordinated mechanical motor performance of longitudinal and circular smooth muscle layer of the ureter wall. The main aim of this study was to characterize in smooth muscle of proximal segments of human ureter, the mechanical properties at level of muscle tissue and at level of myosin molecular motors. Methods Ureteral samples were collected from 15 patients, who underwent nephrectomy for renal cancer. Smooth muscle strips longitudinally and circularly oriented from proximal segments of human ureter were used for the in vitro experiments. Mechanical indices including the maximum unloaded shortening velocity (Vmax), and the maximum isometric tension (P0) normalized per cross-sectional area, were determined in vitro determined in electrically evoked contractions of longitudinal and circular smooth muscle strips. Myosin cross-bridge (CB) number per mm2 (Ψ) the elementary force per single CB (Ψ) and kinetic parameters were calculated in muscle strips, using Huxleys equations adapted to nonsarcomeric muscles. Results Longitudinal smooth muscle strips exhibited a significantly (p<0.05) faster Vmax (63%) and a higher P0 (40%), if compared to circular strips. Moreover, longitudinal muscle strips showed a significantly higher unitary force (Ψ) per CB. However, no significant differences were observed in CB number, the attachment (f1) and the detachment (g2) rate constants between longitudinal and circular muscle strips. Conclusions The main result obtained in the present work documents that the mechanical, energetic and unitary forces per CB of longitudinal layer of proximal ureter are better compared to the circular one; these preliminary findings suggested, unlike intestinal smooth muscle, a major role of longitudinal smooth muscle layer in the ureter peristalsis.