Importance of calcium in the actions of some drugs that stimulate the isolated hypodynamic frog heart.

Eight drugs that stimulate the isolated hypodynamic frog heart have been tested for their ability to stimulate hearts freshly perfused in calcium-free Ringer solution. Ouabain and digitoxigenin regularly caused stimulation, veratridine did so occasionally. Hydrogen peroxide, tannic acid, paullinia tannin (from Paullinia pinnata, Linn.), sodium oleate and sodium caprylate did not stimulate. The stimulant action of ouabain could be prevented or greatly reduced by prior perfusion with either of the two tannins or with hydrogen peroxide. Hearts perfused for 3 to 4 hr with calcium-free Ringer solution, or hearts perfused for shorter periods of time with calcium-free Ringer solution containing the disodium salt of ethylenediaminetetra-acetic acid, behave unusually in that when perfusion with low-calcium Ringer solution is resumed twitch tension does not return for periods ranging from 10 to 90 min. Ouabain is unable to stimulate these "calcium-depleted" hearts. It is suggested that hydrogen peroxide, the two tannins, oleate and caprylate stimulate by causing the heart to increase the uptake of calcium from the perfusion fluid to a superficial site where calcium is necessary for the propagation of excitation from the cell membrane inwards. A special feature of the action of cardiac glycosides may be their ability to enable the heart to utilize in a similar way the intracellular stores of calcium.