Protective effects of trimetazidine in transient spinal cord ischemia

Abstract

The neuroprotective effect of trimetazidine (TMZ) was tested prospectively in a rabbit spinal cord ischemia model. Ischemia was induced by clamping the aorta just distal to the left renal artery and proximal aortic bifurcation for 20 min. Twenty-five male New Zealand white rabbits were randomized as follows: TMZ group (n = 10) receiving 3 mg/kg trimetazidine intravenously before the occlusion of the aorta; control group undergoing occlusion but receiving no pharmacologic intervention (n = 10); sham-operation group (n = 5) subjected to operative dissections without aortic occlusion. Physiological parameters and somatosensory evoked potentials (SEP) were monitored in animals before the ischemia, during the ischemia and in the 1st, 15th and 60th min of reperfusion. Neurologic status was assessed 24 and 48 h after the operation. The spinal cord, abdominal aorta, and its branches were processed for histopathologic examinations 48 h after the operation. At the end of the ischemic period, the average N1-P1 amplitude was reduced to 22% of the baseline in all ischemic animals. This was followed by a gradual return to 90 +/- 2% of the initial amplitude in the TMZ group and 81 +/- 2% in the control group (P < 0.05) after 60 min of reperfusion. The average motor function score was significantly higher in the TMZ group than the control group (3.7 +/- 0.5 vs 3.1 +/- 0.6 at 24 and 3.5 +/- 0.7 vs 2.9 +/- 0.6 at 48 h; P < 0.05). Histologic observations were clearly correlated with the neurologic findings. The results suggest that trimetazidine reduces spinal cord injury during thoracoabdominal aortic operations and may have therapeutic utility during high risk operations.