Mitochondrial changes induced by trimetazidine in the myocardium

The aim was to assess the effect of trimetazidine (TMZ) on mitochondrial alterations induced in a canine model of brief, repeated episodes of ischemia.

Twelve crossbred dogs were analyzed, after double-blind randomization, to a 7-day treatment with either TMZ or placebo. Twenty brief, complete occlusions of the left anterior descending coronary artery were performed. Mitochondrial analysis entailed a qualitative (percentage of mitochondrial damage, merging, pairing, vacuoles, and lipofucsin granules) and a quantitative size analysis (major and minor axes, perimeter, and area) of the mitochondria in the ischemic and control zones.

Comparative study of the control zones revealed an increase in lipofucsin granules in the TMZ series and a greater percentage of damaged mitochondria and vacuoles. The control-zone mitochondria treated with TMZ presented a significant increase in the perimeter and major axis and a decrease in the minor axis (p<0.005). No significant differences were found between the series in the qualitative analysis of mitochondrial damage in the ischemic zone. The mitochondria in the TMZ series presented a greater major axis and perimeter than those in the placebo series (p<0.05), which presented a smaller minor axis.

TMZ made the mitochondria adopt an elongated, "rod-like" morphology in both the control and ischemic zones. This is interpreted as an increase in the membrane surface. In the non-ischemic zone, TMZ produced an increase in mitochondrial turnover. There were no differences in the myocardium subjected to ischemia in both series in terms of observable mitochondrial damage.