• Journal of Chest Surgery
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• v.35 no.4
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• pp.255-260
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• 2002

Paraplegia remains unresolved as the most dreaded operative complication with surgical treatment of descending thoracic and thoracoabdominal aortic diseases. In this study, the neuroprotective effect of trimetazidine that has been used clinically for ischemic heart disease was investigated in a rabbit spinal cord ischemia model. Material and Method: Thirty-three New Zealand white rabbits were randomized as follows: control group undergoing abdominal aortic occlusion but receiving no pharmacologic intervention(Group 1, n= 17); TMZ group(Group 2, n= 16) receiving 3 mg/kg trimetazidine intravenously before the occlusion of the aorta. Ischemia was induced by clamping the abdominal aorta just distal to the left renal artery for 30 minutes. Neurologic status was assessed at 2, 24, and 48 hours after the operation according to the modified Tarlov scale, then the lumbosacral spinal cord was processed for histopathologic examinations 48 hours after the final assessment. Result: The average motor function score was significantly higher in the TMZ group(3.20 $\pm$ 0.77 vs 1.13 $\pm$ 1.25 at 2 hours, 3.50 $\pm$ 0.76 vs 1.45 $\pm$ 1.57 at 24 hours, and 3.91 $\pm$ 0.30 vs 1.86 $\pm$ 1.86 at 48 hours after operation; p value$\leq$0.05). Histologic observations were correlated with the motor scores. Conclusion: The results suggested that trimetazidine reduced spinal cord injury during aortic clamping and that it may have clinical utility for the thoracoabdominal aortic surgery:

• Archives of Pharmacal Research
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• v.27 no.6
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• pp.646-652
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• 2004

The objective of this study was to determine the acute effect of trimetazidine (TMZ) on the pre-fatigue, fatigue and post-fatigue contractile characteristics and tension-frequency relationships of isolated rat diaphragm muscle. Muscle strips were taken from the ventral-costal aspects of the diaphragm muscle of rats killed by decapitation. The muscle strips were suspended in organ baths containing Krebs solution, with a gas mixture of 95% $O_2$ and 5% $CO_2$ at $37^{\circ}C$ and pH 7.35-7.45. After determining the thermoregulation and optimum muscle length the muscles were subjected to direct supramaximal stimulation with 0.05 Hz frequency square pulses for periods of 0.5 msec to obtain control values. After adding $5{\times}10^{-6}{\;}and{\;}5{\times}10^{-5}$ M trimetazidine solution to the respective bath media, the contractile parameters of the muscles were recorded. The contractile parameters were also recorded for both the trimetazidine and tri-metazidine-free media after application of the high frequency fatigue protocols. Later, the tension-frequency relationship was determined by applying stimulating pulses of 10, 20, 50 and 100 Hz to the muscle strips. Whilst the twitch tension obtained from the $5{\times}10^{-6}{\;}and{\;}5{\times}10^{-5}$ M trimetazidine media showed numerical increases compared to that of the controls, these were not statistically significant (p>0.05). The contraction time exhibited a dose dependent increase (p<0.001), whilst the contraction and relaxation rates did not differ significantly. The isometric contraction forces obtained with the different stimulating frequencies showed a significant increase in the tetanic contraction only at 100 Hz (p<0.05). A comparison of the pre- and post-fatigue twitch tensions in the trimetazidine media showed the post- fatigue twitch tensions to be significantly higher than those of the pre-fatigue contraction forces (p<0.05). In the $5{\times}10^{-6}{\;}and{\;}5{\times}10^{-5}$ M trimetazidine media the increases in the post-fatigue contraction force were 22 and 30%, respectively. These results demonstrated that in isolated rat diaphragm muscle, TMZ significantly limited the mechanical performance decrease during fatigue. It is our opinion that trimetazidine contributed to the observed fatigue tolerance by eliminating the factors of fatigue, due to preservation of intracellular calcium homeostasis, provision of the ATP energy levels needed by ATPase dependent pumps and especially by keeping the intracellular pH within cer-tain limits.