[Platelet Metabolism in Clopidogrel Resistant and Sensitive Patients With Ischemic Heart Disease]

to investigate relationship between activity of platelet nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP) dependent dehydrogenases in patients with ischemic heart disease (IHD) after coronary artery bypass grafting (CABG) and their sensitivity to clopidogrel.

We studied 51 male patients with chronic IHD before and after CABG. Control group comprised 35 healthy men. In IHD patients spontaneous and induced platelet aggregation was measured by aggregometry before CABG (in 2 weeks after cessation of antiplatelet drugs), after CABG during therapy with clopidogrel (75 mg/day), and in 6 months after surgery. Patients were classified as clopidogrel sensitive or resistant using cutoff of 50% inhibition of initial ADP (5 M) induced platelet aggregation after 2 weeks of treatment with clopidogrel. Activity of platelet NAD and NADP dependent dehydrogenases was measured by bioluminescent method.

There were 41 clopidogrel sensitive and 10 clopidogrel resistant patients. Irrespective of sensitivity to clopidogrel platelet metabolism in IHD patients was characterized by reduced activity of anaerobic energetics, glutathione-dependent antioxidant system, reactions that transport products of lipid catabolism on glycolysis, and NADPH-dependent transfer of substrates from citric acid cycle to amino acid metabolism. Metabolic features of platelets characteristic of clopidogrel resistance were low activity of the key reaction of pentose phosphate cycle reflecting state of plastic metabolism, and substrate flow in the tricarbonic acid cycle - determinant of intensity of aerobic energy. Clopidogrel-sensitive patients had increased platelets NADP-malate dehydrogenase activity (the key reaction of lipid anabolism).