Potential beneficial effects of potassium channel blockade by tedisamil in isolated perfused working rat heart with coronary artery ligation

Abstract

Tedisamil, a potassium channel blocker, is known to produce bradycardia. The hypothesis tested was that tedisamil-induced bradycardia should improve the mechanical and metabolic properties of the ischemic myocardium. Using isolated perfused rat heart with coronary-artery ligation, tedisamil was compared with alinidine, verapamil, and propranolol. The end points were myocardial mechanical function and oxygen uptake. In coronary-ligated hearts, tedisamil (1.83×10-6 M) decreased heart rate, increased left ventricular dP/dtmax, and increased pressure power production. Efficiency of work rose with tedisamil. Alinidine (7×10-6 M) also decreased heart rate without altering left ventricular dP/dtmax, power production, or myocardial efficiency. Verapamil (1.5×10-7 M) did not alter heart rate but decreased left ventricular dP/dtmax, while power production and myocardial efficiency also fell. Propranolol (1×10-5 M) caused changes similar to verapamil, except that the heart rate also fell. Dobutamine (1.18×10-7 M) increased cardiac output and oxygen uptake without altering mechanical efficiency. Of the drugs tested and in the concentrations used in the coronary ligated rat heart, it was only tedisamil that had the capacity to cause less decrease in mechanical work and in myocardial efficiency than in controls.