Tedisamil attenuates foetal transformation of myosin in the hypertrophied rat myocardium.

1 Reduction in repolarizing potassium currents has controversial effects on hypertrophic responses in cardiomyocytes of transgenic models and cultured cardiomyocytes. It remains thus unknown whether a blockade of potassium channels with tedisamil (N,N'dicyclopropylmethylene-9,9-tetramethylene-3,7-diazabicyclo(3.3.1)nonane dihydrochloride) has any effects on cardiac growth during postnatal development or pressure overload. 2 To test the hypothesis that a treatment with tedisamil affects cardiac growth or protein phenotype, sham-operated rats and rats with ascending aorta constriction were treated with tedisamil (36 mg kg day(-1)) for 7 weeks. Left ventricular mass and geometry, relative expression of myosin isoforms, hydroxyproline concentration and isovolumic ventricular function were assessed. 3 Rats with aortic constriction exhibited a marked increase in left ventricular weight and the diastolic pressure-volume relationship was shifted to smaller volumes. The hydroxyproline concentration remained unaltered. The proportion of alpha-myosin heavy chains was, however, reduced (P<0.05). Hypertrophied left ventricles manifested an enhanced overall performance but depressed myocardial contractility. 4 Administration of tedisamil was associated with decreased heart rate (P<0.05). In contrast, cardiac growth in sham-operated rats and concentric left ventricular hypertrophy of pressure-overloaded animals was not significantly altered. Hypertrophied hearts from rats treated with tedisamil expressed more alpha-myosin heavy chains (65+/-4 versus 57+/-4%; P<0.05). Also, maximal rate of wall stress rise and decline was higher (P<0.05) in tedisamil-treated pressure-overloaded rats. 5 In the rat model of pressure-overloaded hypertrophy, tedisamil had no effect on cardiac growth but partially corrected myocardial dysfunction. Postulated mechanism of this effect is the phenotype modification of myosin filaments in hypertrophied myocardium.