Sympathomimetic Activity in the Isolated Frog's Heart (Rana Temporaria)

1. It was found that addition of ascorbic acid or an extract of frog's liver to the medium perfusing hearts showing a linear, low Q10, temperature-pulse rate curve (type E) led to an increased frequency response at the higher temperatures. By such treatment curves of types A, B or D were obtained (Smith, 1951). 2. In nearly all cases it was necessary to add adrenaline (1 in 107) to the perfusate to obtain an early response of this nature. In the absence of external adrenaline a similar change was observed after longer treatment with ascorbic acid or liver extract (up to 20 hr.). The possible action of adrenaline in this respect is discussed, and it is suggested that it may afford protection to sympathomimetic substances in the heart tissues. 3. The occurrence of a decreasing acceleration of pulse rate at higher temperatures in certain types of hearts was observed. This phenomenon was reversible on lowering the temperature again, but there was a marked time lag before equilibrium was re-established. When such hearts were treated with ascorbic acid or liver extract, and type A or B curves produced, the direction of this delayed pulse rate change was reversed. The significance of this behaviour in relation to the hypothesis that sympathomimetic substances are synthesized by the isolated heart is discussed. 4. It is suggested that the observed modifications of the type E curve produced by treatment with anterior pituitary extract, liver extract, or ascorbic acid were due to their action in promoting synthesis of adrenergic material by the heart. In the case of ascorbic acid there was evidence for an additional protective action. 5. It was found that treatment of types A or B hearts with ergotoxine and iodoacetic acid caused a definite change of the temperature-pulse rate curve towards the type E form. 6. Temperature-amplitude curves were constructed for numerous hearts of various types, and it was found that distinct forms occurred in correlation with the different types of temperature-pulse rate curves. It has been shown that the frequency and amplitude changes are related in such a way that they can both be attributed to production or inactivation of sympathomimetic substances. 7. The action of thyroxine in modifying the form of the temperature-pulse rate curve is attributed to its protective action on adrenergically active compounds. 8. An analysis of the various forms of temperature-pulse rate curve has been made on the basis of the action of temperature on three independent systems: (i) the pacemaker mechanism of the heart, (ii) the synthesis of sympathomimetic material, and (iii) the rate of inactivation of such material. In the summer heart (type C) synthesis is active and the material formed is protected by the relatively high level of circulating thyroid hormone. In the winter (type A) form, owing to the lower activity of the thyroid, the effects of inactivation lead to an exponential relation between pulse rate and frequency. Prior to the breeding season and in female frogs in the autumn there is apparently defective synthesis of adrenergic material and the type E relation appears. In January and February this type is often further modified, owing to thyroid inactivity, so that a constant acceleration is not maintained over the whole temperature range.