RESEARCHES ON THE PERFUSED HEART: SOME EFFECTS OF SODIUM CHLORIDE

Abstract

An active displacement of calcium salts by sodium is a factor in the production of the diastolic failure which follows perfusion of isotonic sodium chloride through the frog's heart.After perfusion of isotonic sodium chloride through the frog's heart— 1. The action of calcium salts in shortening the refractory period, 2. The action of the same salts in producing tonus, 3. Their action in supporting the spontaneous contractions, is greatly increased in each case.Reasons are given for believing that these changes result from alterations in the state of aggregation of certain of the heart colloids.The changes of aggregation state induced by isotonic sodium chloride are, thus, favourable to these functional activities of calcium.Hearts perfused with mixtures of sodium and calcium salts eventually cease activity in diastolic failure, though this failure may be complicated by a primary increase of tonus. When examined at the end of this failure the heart shows a greatly diminished responsiveness to calcium salts. Reasons are given for believing this latter condition is due to the calcium salts in the original perfusing solution, and the conclusion drawn that calcium salts induce an aggregation state in certain heart colloids unfavourable to the more immediately apparent normal functional activity of these salts.The immediate stimulating effects of hypotonicity described by Carlson depend on the calcium salts in the perfusing solution. They vary in intensity according to the concentration of the calcium in the solutions. They are not due to hypotonicity per se, since they also occur if the osmotic pressure be kept constant by cane‐sugar. Removal of the restraint previously exercised by the sodium salts of the perfusing solution over its calcium is an important factor in this “stimulating action” of hypotonicity.Following on these primary changes are secondary ones in which the effective action of a given concentration of calcium salts in producing tonus, etc., is greatly diminished. On returning now to normal sodium chloride there is a sudden further diminution in the effective action of a given concentration of calcium, followed still later by a gradual and slow return towards the condition existing before the reduction in sodium chloride content.On perfusing a solution containing excess of sodium chloride (hypertonic), there is an immediate fall in the effective action of the calcium salts already present in the solution. Following on these changes the effective action of the calcium salts is greatly increased. The refractory period may be shortened sufficiently to permit of an apparently complete tetanus of the heart muscle. Summation of contractions is possible. The tonus may be greatly increased.On restoring the sodium chloride to normal there is a primary exaggeration of the effects just mentioned, the increased tonus changes sometimes simulating a “veratria” contraction. The effective action of a given concentration of calcium salts then decreases to a point where they may be less efficient than they had been before the hypertonic solution was perfused. After this overshoot the effective action of the calcium slowly returns towards the normal.The perfusion of a solution made hypertonic by adding cane‐sugar also increases the effective action of a given concentration of calcium, though not in similar degree to that induced by sodium chloride.Twofold relations exist in the heart between the salts of sodium and calcium. They are antagonistic in regard to their mutual adsorption on the surface of certain of the heart colloids (surface effects); they are antagonistic in regard to the changes in the state of aggregation each induces in those same colloids (deep effects). The state of aggregation induced by calcium is one unfavourable to its own activity in its function of tonus production, etc.; the state of aggregation induced by sodium favour these latter functions of calcium. The favouring action of sodium on these calcium functions outweighs its antagonism.Hence, if the amount of sodium chloride in a perfusing solution be increased, the effective action, in certain directions, of the calcium salts already present in that solution will also be increased, but at a distinctly later period, and vice versâ.In conclusion, I wish to express my indebtedness to Professor Sherrington for the facilities afforded me in carrying out this work.