Effects of trimetazidine and selenium on high-frequency fatigue in isolated rat diaphragm muscle

Trimetazidine (TMZ), which has been used in numerous experimental studies, is applied nowadays with the aim of reducing myocardial ischemia. The aim of this study was to determine the prefatigue and postfatigue contractile characteristics associated with the relationship between the force and frequency of contraction in muscle. The study was conducted using diaphragm muscle isolated from 40 male Wistar rats weighing 230 to 270 g. The rats were divided into 4 groups of 10 animals each: controls and TMZ-, selenium (Se)-, and TMZ+Se-treated groups. The rats in the control group were treated with 2 mL of physiologic serum (SF), those in the second group with Se 30 microg/kg in 2mL of SF, those in the third group with TMZ 5 mg/kg in 2 mL of SF, and those in the fourth group with a combination of TMZ 5 mg/kg + Se 30 microg/kg in 2 mL of SF. All rats were treated twice daily for 15 days by means of gastric lavage. The rats were then killed by cervical dislocation. The diaphragm muscle bands were removed and placed in an organ bath. After a 2-hour thermoregulatory period, muscles were fatigued with 5-ms pulses at a frequency of 40 Hz. Force-frequency relationships were studied after the application of 10, 50, and 100 Hz and the development of contraction curves. Contraction forces for the groups treated with TMZ, Se, and TMZ+Se (16.1 +/- 1.2, 13.2 +/- 1.3, and 14.9 +/- 1.0 g, respectively) were significantly lower than for the control group (17.0 +/- 1.4 g) during the prefatigue period (P<.001). Similarly, postfatigue contraction forces for the treated groups (15.7 +/- 1.3, 8.8 +/- 1.0, and 12.0 +/- 1.4 g, respectively) were significantly lower than for the control group (12.4 +/- 1.2 g, P<.001, P<.001, and P<.05, respectively). A significant decrease was noted in postfatigue contraction forces and contraction and relaxation rates in the Se- and TMZ+Se-treated groups compared with prefatigue values (P<.001), but the difference was not significant. Force-frequency relationships were evaluated at 10, 50, and 100 Hz. The tetanic contraction forces for the control, Se-, TMZ-, and TMZ+Se-treated groups at 100 Hz were 81.3 +/- 5.7, 91.6 +/- 6.8, 65.3 +/- 5.0, and 84.9 +/- 7.5 g, respectively. In the TMZ-treated group, a significant increase was observed in tetanic contraction forces at 100 Hz compared with controls (P<.001); no significant changes were seen in the force-frequency relationships at 10 and 50 Hz. The decrease in the contraction force in the postfatigue period was prevented to a larger extent in the TMZ-treated group than in the TMZ+Se- and Se-treated groups.