Adrenal Insufficiency and Capacity for Sustained Work Output

Abstract

During the past 2 years the writer has been investigating work output of adrenalectomized rats with the object of evaluating work capacity as a criterion of adrenal cortex insufficiency. Other questions which we hope to answer are: is the medulla necessary to maintain capacity for normal work? will the injection of extracts completely replace the role of the normally functioning cortex? and, is nervous innervation necessary for the normal secretory activity of the cortex? Several findings seem to be reliably established and to deserve report.

We have previously made a brief report on methods. 1 The gastrocnemius muscle of an intact animal is loaded with 100 gm. and is forced to contract 3 times per second by faradic stimulation. The animal is anesthetized with sodium luminal. Our setup allows temperature and humidity control. Four animals may be worked simultaneously, the electrodes to each animal being connected in series allowing the same impulse to stimulate each animal. Automatic recording devices are used. Each animal receives 5 cc. of a 10% dextrose solution through subcutaneous injection every 6 hours. Under these conditions normal animals may be relied upon to work continuously with only a small decrease, if any, in rate of energy output for a minimum of 5 days. By administration of large amounts of dextrose and some protein we have been able to extend the length of minimum work period to 11 days.

Of 35 adrenalectomized animals kept under optimum living conditions 32 died in an average time of 15 days with a range of 4 to 30 days. For 30 adrenalectomized animals which were worked immediately following operation complete “fatigue” took place in an average time of 15 hours with a range of 4 to 33 hours. These animals succumbed in an average time of 2 hours following “fatigue”. The 3 animals from the first mentioned group which had survived adrenalectomy for an excess of 30 days and who were normal in weight, appearance, and behavior all “fatigued” and died within 20 hours after beginning work. From this observation and the additional one that control animals subjected to severe sham operations work and survive as normals we regard the effect of operation itself as of small consequence. It was definitely established that maintenance of anesthesia was a most important factor along with work performance in bringing about this rapid manifestation of adrenal insufficiency.

Administration of an adrenal cortex extract prepared by E. C. Kendall∗ gave striking results. Small doses were effective in prolonging the survival period and increasing the amount of work done. It was possible to bring about temporary recovery from complete “fatigue”. Large doses (1/2 cc. every 6 hours) given to an animal whose work period began immediately following operation prolonged the period of muscular contraction to 145 hours and the survival period to 147 hours. Although the work done was somewhat less than that accomplished by any normal animal, this survival period compares favorably with that expected of a normal animal under these conditions. With further experimentation on dosage we hope to evaluate adequately the capacity of such cortex hormone preparations to maintain a normal energy output in adrenalectomized rats.