Abstract

1. In pithed frogs, increase of temperature increases the rate of the heart as an asymptotic but not simply logarithmic curve until intermittence is reached. The form of this curve appears essentially similar for the American and European species; it is also essentially the same when the heart is empty, when it is stimulated by the distention of perfusion, and when it is further quickened by accelerator stimulation, through the nerve or through epinephrine. These alter the level, but not materially the form of the curve.

2. Increase of temperature also increases the amplitude of the excursions of the perfused heart. The amplitude increase, however, is reciprocal to the rate increase. At the lower range of temperatures, the rate increases more rapidly than the amplitude; at the upper range, the amplitude comes to predominate over the rate.

3. The rate-response to the stimulant concentration of epinephrine (1:10⁷) increases with the temperature, until heat-intermittence is reached. The acceleration by heat and by epinephrine are therefore not only fully additive but even augmentive, so that not only the actual but even the percentile rate-response to epinephrine increases with warming, up to a fairly high temperature. This may be called "augmented summation," since it is magnified beyond the simple sum of the actions.

4. The heat-increment of the epinephrine response is not due to increased reaction-velocity between the heart and epinephrine; since exactly the same curve holds for stimulation of the accelerator nerve. The increase of augmentor response with temperature must therefore be due to increased excitability of the heart itself.

5. The augmented summation of the heat and epinephrine stimulation is in marked contrast to the summation of the epinephrine and accelerator nerve stimulation; for the latter is only complementary: The maximal response to simultaneous stimulation by both agents is not materially greater than the response to either agent alone; so that, as the strength of the stimulation by one agent is increased, the response of the other agent diminishes. This radical difference indicates that the increase of heart rate by rise of temperature does not occur through the sympathetic accelerator mechanism, for if it did, the summation would be complementary instead of being potentiated.

6. At a given temperature, the heart-rate of different (pithed) frogs varies within 20 per cent above and below the median rate. The rate acceleration by epinephrine stimulation increases with the natural rate, but the sum of the natural rate and the epinephrine increase does not materially surpass the limit set by the median accelerated rate at each temperature; and when this limit is reached, the epinephrine acceleration decreases with increase of the natural rate, so as to stay within the limit. The epinephrine therefore shows two kinds of summation with the natural rate of the heart: augmented (like temperature) for the lower rates; and complemental (like accelerator stimulation) for the higher rates. From this it appears likely that at a given temperature abnormally low heart rates are due to deficient rhythmic vigor of the heart muscle, which therefore also responds relatively poorly to epinephrine; while abnormally high heart rates, which give complemental summation with epinephrine, are apparently due to high activity or spontaneous stimulation of the accelerator mechanism either in the ganglia or in the heart-muscle. The conception of peripheral accelerator tone is perhaps rather novel, but it is quite in consonance with the self-government of the autonomic system.

7. Excessive heat tends to produce intermittence or blocking of the cardiac rhythm. This may be either relieved or exaggerated by epinephrine, according to the relative predominance of accelerator stimulation and of muscular energy. Often both effects appear, in succession or alternation. The heat and epinephrine injury show augmented summation: The higher the temperature above the critical level, i.e., the greater the heat-injury, the more is the intermittence exaggerated by dilute epinephrine; whilst higher concentrations of epinephrine lower the critical temperature.