Background: This study was undertaken to characterize the effects of tedisamil on isolated rat cardiovascular tissues, and identify actions that could be beneficial or detrimental in the treatment of cardiac disease.
Results: Tedisamil prolonged the Wistar Kyoto normotensive rat (WKY) left ventricular action potential and augmented the force of contraction of left ventricle strips. On the 12-month-old SHR model of cardiac hypertrophy, the augmenting effects of tedisamil at 10(-6) and 3 x 10(-6) M were reduced. On the 21-month-old SHR model of heart failure, the augmenting effects of tedisamil at 10(-6) and 3 x 10(-6) M were further reduced. The augmenting effect of tedisamil at 10(-5) M was reduced to 47%. The rate of the right atrium of 16- to 17-month-old WKY was reduced by tedisamil at 10(-5) and 10(-4) M, and tedisamil had a similar effect on the SHR right atrium. Tedisamil at 10(-6)--3 x 10(-5) M contracted the portal veins of WKY and aortae of 12-month-old WKY and SHR.
Conclusions: The positive inotropic and negative chronotropic effects of tedisamil in the rat, which are partially or fully maintained in hypertrophied or failing myocardium would be beneficial in the treatment of heart failure. In contrast, the vasoconstrictor action of tedisamil will be detrimental in heart failure.