The effect of mephentermine on isolated dog hearts, normal and pretreated with reserpine.

The inotropic activity of the non-catechol sympathomimetic amine, mephentermine sulphate, on the failing dog heart-lung preparation, was 1/10 to 1/20 that of adrenaline. Mephentermine showed no inotropic effect on preparations from animals pretreated with reserpine. The chronotropic and "calorigenic" actions of mephentermine were tested on modified heart-lung preparations to permit a more accurate measurement of coronary flow, and were found to be greater than its inotropic effect relative to adrenaline. Furthermore, the action of mephentermine was longerlasting than that of adrenaline. If adrenaline was infused 15 min after the termination of mephentermine administration and when the action of the latter was still at a maximum, a further increase in heart rate and especially oxygen consumption was observed. In preparations from dogs treated with enough reserpine to deplete the heart of noradrenaline, mephentermine had only slight chronotropic and calorigenic actions. However, further addition of adrenaline after a 15 min pause caused a rise in heart rate, oxygen consumption, and coronary flow which almost duplicated the additive effects of both amines on the preparations not treated with reserpine. It would appear that adrenaline acted on its own and in addition "restored" the action of mephentermine on the reserpinized preparations. The action of adrenaline alone on reserpinized preparations was not increased compared with that on normal preparations. These observations are relevant to a consideration of the mechanism of action of non-catechol sympathomimetic amines on the heart, and are in harmony with the concept that mephentermine, a non-catechol amine, requires the presence of added or stored catechol amines for its action. Reserpine treatment did not alter the mechanical efficiency of the heart despite its depletion of noradrenaline.