Effects of trimethazidine on brain metabolism in acute ischemia combined with hypoxia

Abstract

Trimethazidine in a dose of 25 mg/kg prevents disturbances of energy metabolism and activation of lipid peroxidation in rat brain after acute ischemia and hypoxia. Our objective was to study the protective effects of TM under conditions of acute brain ischemia complicated with hypoxia. This combination occurs when acute disorders of cerebral circulation are accompanied by respiratory deficiency of central origin.[11]: of both common carotid arteries under ether anesthesia. The animals were then elevated to an altitude of 8000 m in a pressure chamber tot 90 rain. The brain was fixed by immersing the head in liquid nitrogen. The metabolic state of cerebral hemispheres was assessed by measuring the content of glycogen, glucose, pyruvate, lactate [7], creatine phosphate [1], ATP, ADP, AMP, and inorganic phosphate, and by determining the energy potential of the adenine nucleotide system [4]. The intensity of lipid peroxidation (LPO) was assessed by the content of lipid peroxides and malonic dialdehyde. The functioning of the antioxidant system was assessed by the content of reduced glutathione and catalase and superoxide dismutase (SOD) activities as described previously [8]. The data were analyzed statistically using Student's t test. RESULTS MATERIALS AND METHODSExperiments were carried out on adult male rats weighing 180-200 g. Three groups were formed (8 rats in each): 1) sham-operated (control); 2) exposed to acute ischemia and hypoxia; 3) treated with intraperitoneal TM (Vastarel, Biopharm, 25 mg/kg) 30 min prior to ischemia-hypoxia. Ischemia was caused by occlusion Department of Pharmacology, Military Medical Academy, St, Petersburg Occlusion of the carotid arteries in combination with hypoxia caused dramatic changes in brain metabolism (Table 1). Cerebral content of glycogen decreased by 53% with glucose increasing by 44%. Considerable rise in lactate content occurred simultaneously with the decrease in pyruvate content. As a result, the lactate/pyruvate ratio increased more than six-fold, which was indicative of intensified anaerobic glycolysis. It is known that occlusion of the carotid arteries in rats considerably reduced cerebral circulation, and dis-0007-4888/99/0003-0269522.00 9Kluwer Academic/Plenum Publishers