ON THE MECHANISM OF THE POSITIVE INOTROPIC ACTION OF FLUORIDE, OLEATE, AND CALCIUM ON THE FROG'S HEART

¹ Department of Pharmacology, New York University College of Medicine, New York

Sodium fluoride or sodium oleate added in low concentration to the medium restores the normal contractile amplitude of the Strauh heart preparation severely depressed by a variety of conditions.

Since both oleate and fluoride have in common the property of forming insoluble calcium salts and of being strongly fixed to the heart, it seems probable that either forms some complex with a cellular constituent together with calcium and that this complex is responsible for the efficacy of fluoride or oleate as well as of Ca++.

The fact that fluoride and oleate relieve depression that may also be relieved by Ca++ increase suggests that in these cases the susceptibility of the heart to the action of calcium is impaired and that fluoride and oleate restore the normal susceptibility. As calcium combines and reacts with the cell membrane the fixation and function of fluoride and oleate too is presumably located there.

Fluoride and oleate are effective also in circumstances in which diminution of amplitude is produced by excessive calcium effect. It is concluded, therefore, that in depression in general, the state of the cell membrane is impaired and that oleate and fluoride restore not specifically calcium sensitivity but restore the normal state of the membrane and hereby the calcium sensitivity.