Haemodynamic and metabolic effects of low daily dose sulphonylureas in diabetic dog hearts

The effects of glibenclamide (GB, CAS 10238-21-8) and those of the latest low daily dose sulphonylurea compound, glimepiride (GM, CAS 93479-97-1) on myocardial haemodynamics and pyruvatelactate metabolism of healthy and alloxan-diabetic dogs (n = 6 in six groups) were compared. Mean arterial blood pressure, heart rate, blood flow of the left anterior descending coronary artery, myocardial contractile force, the rate of change of myocardial contraction and relaxation were measured and arterial (a. carotis communis) and venous (sinus coronarius) pyruvate and lactate concentrations were determined during i.v. administration of the drugs (0, 0.4, 2, 5, and 8 µmol/kg). Coronary conductivity, pressure-rate product and pyruvate-lactate extraction rates were calculated. Glimepiride reduced the heart rate in diabetic animals. Both compounds decreased myocardial contractile force, coronary blood flow and conductivity and the rate of change of myocardial contraction. However, alterations in blood pressure, pressure-rate product, the rate of change of myocardial relaxation and arterio-venous lactate difference elicited by glibenclamide proved to be more expressed than those by glimepiride. According to the results, glibenclamide and especially glimepiride do not enhance the disturbances of the cardiovascular system in diabetes. By this reason, considering its very low daily dose and favourable haemodynamic effects, glimepiride could preferably be recommended for the treatment of type 2 diabetics with coronary heart disease.