EFFECTS OF ATROPINE AND PILOCARPINE ON HUMAN THERMOREGULATION* by Dr. Edward D."Palmes, Biochemist, H. G, Schachner, Capt., M.C., Roy E, Albert, 1st Lt,, M.C., and J. J. Hart, Tec, 4 from Medical Department Field Research Laboratory Fort Knox, Kentucky 14 April 1948 *Sub-proJect under Studies of Body Reactions and Requirements under Varied Environmental and Climatic Conditions. Approved 31 May 1946. MDFKL Project No. 6-64-12-06-(8). Project No. 6-64-12-06 Sub-project MDFRL 06-8 MEDEA Ik April 1948 ABSTRACT EFFECTS OF ATROPINE AND PILOCARPINE ON HUMAN THERMOREGULATION OBJECT To determine the manner and extent of compensation to the thermal stresses imposed by the injection of atropine and pilocarpine. RESULTS Complete thermal balance studies were made on subjects before and after subcutaneous injection of these drugs at two different ambient temperatures. CONCLUSIONS Changes in evaporative rate produced by these drugs,are thermally compensated by alterations in convection and radiation and, under some conditions, in peripheral blood flow and metabolism. The compensatory mechanisms are not sufficiently prompt nor large enough to maintain thermal balance immediately after the injection. They persist, how- ever, much longer than does the altered evaporative rate. The r,atropine flush11 is a reaction secondary to a reduction in evaporative rate, RECOMMEND ATIONS None. Submitted by; Edyrard D. Palmes, Ph.D,, Biochemist. H, G. Schachner, Capt,, M.C. Roy E. Albert, 1st Lt,, M.C. J. J, Hart, Tec A. Approved c/y pfesSRICK J. KNOBLAUCH Lt. Col., M.C. Commanding EFFECTS OF ATROPINE AND PILOCARPINE ON HUMAN THERMOREGULATION I. INTRODUCTION V The administration of atropine inhibits, and pilocarpine increases, sweat secretion (l, 2). Since sweat secretion is an important regula- tor of heat loss (3, 4, 5), any change in sweat rate, if uncompensated, should produce a change in body heat content. It was of interest, therefore, to determine the manner and extent of compensation to the thermal stresses Imposed by the administration of these drugs. Since sweat rate is influenced by the ambient temperature, it was desirable to determine whether or not the thermal effects of these drugs are altered by varying the environmental temperature. Sweating at 29°C. is normally minimal or absent (6), while in an ambient temp- erature of 38°C., evaporation is the only route of heat loss, II. EXPERIMENTAL A, Apparatus and Methods The method of human calorimetry used here is the same as that employed previously at this laboratory (?). The subject lay on a waterproof netting in a ventilated chamber and breathed into a closed circuit metabolism apparatus. Evaporative rate was recorded contin- uously by an infrared gas analyzer (S), Air, wall, rectal and skin temperatures were measured by thermocouples C9)• Each of tv/o subjects received 1 rag. atropine sulfate subcutaneously at ambient temperatures of 29 and 38°C., and each of two other subjects received 10 mg. pilocarpine hydrochloride by the same route at the same temperatures. In 4 of the 8 runs, the subjects reported in a poatabsorptive state; in the remainder they had eaten breakfast. After disrobing they rested for one-half hour before entering the calorimeter. Control observations were then made until all measurements seemed to roach constant values (l to 2 hours), whereupon the injection was given. Following the injection, measurements were continued until they ap- proached the control values (l to 4 hours). A complete thermal balance was calculated for each experiment; peripheral blood flow was obtained from the thermal data by the method of Hardy and Soderstrom (6), B, Results The results shown in Figures 1 and 2 are plotted as average values for 12 minute periods and the vertical broken lines indicate the times of injection. No eseential difference was found in the results on basal and nonbasal subjects. One graph of each pilocarpine and atropine run at 32°C, is shown as representative of the data obtained; although the magnitude of the individual thermal responses differed in duplicate runs, the essential pattern of compensatory reactions was the same. 1. Pilocarpine. a. Ambient temperature 38°C. (Figure l)♦ Almost immediately after the injection the evapor- ative rate rose rapidly, reached a peak in 12 to 2U minutes, and returned to normal values US to 60 minutes post injection. As a result of the increased evaporative cooling, skin temperature fell markedly. The fall in skin temperature increased heat gain by convection and radiation, A small increase in heat gain was also obtained by a rise in the metabolic rate due to shivering. Peripheral blood flow was decreased, preventing heat loss from the deep tissues. As a resultant of all changes the heat content of the body fell, reaching a minimum about one-half hour after injection and returning slowly to the control value thereafter. There was a fall in rectal temperature which was slaver and smaller than that of the skin. b. Ambient temperature 29°C. The pattern of changes observed at this temperature was the same as that at 3S°C,t except that peripheral blood flow was not reduced significantly. This difference is explained by the fact that peripheral blood flow values were minimal before the injection. 2. Atropine. a. Ambient temperature 3£°C. (Figure 2), Following the injection evaporation fell rapidly, reaching a minimum value 12 to 24 minutes after injection, and returned to normal in 36 to 60 minutes post injection. As a result of the de- creased evaporative cooling, skin temperature rose and this, in turn, reduced heat gain by convection and radiation. Peripheral blood flow showed a very striking increase which aided dissipation of heat from the deep tissues. No change was observed in metabolism. As a result- ant of all changes, the heat content of the body rose, reaching a maximum US minutes after injection and falling slowly thereafter. There was a rise in rectal temperature which was slower and smaller than that of the skin. Marked flushing was observed 20 minutes after injection and persisted for about 2 hours, b. Ambient temperature 29°C. No significant thermal changes were produced by the injection. This is explained by the fact that there was no active sweating during the control period. No flushing was observed. III. SUMMARY AND CONCLUSIONS The primary thermal effect of the subcutaneous injection of atropine and pilocarpine is a change in evaporative rate. The result- ing change in skin temperature brings about alterations in convection and radiation v/hich thermally oppose the change in evaporative rate. Changes in peripheral blood flow and metabolism, if present, also counteract the initial effect. The compensatory mechanisms are not sufficiently prompt nor large enough to maintain thermal balance immediately after the injection. They persist, however, much longer than does the altered sweat rate. Since flushing of the skin after injection of atropine occurred only at the higher ambient temperature, it is concluded that the "atropine flush" is a reaction secondary to a reduction in evaporative rate. IV. BIBLIOGRAPHY 1. Goodman, L. and Gilman, A. The Pharmacological Basis of Therapeutics. New York, Macmillan, 1941. 2. Sollmann, T. A Manual of Pharmacology, 6th Ed., Philadelphia, W, B. Saunders Co., 1942. 3. Wolkin, Julius, Goodman, J. I. and Kelley, W. 2, Failure of the sweat mechanism in the desert; Thermogenic anhidrosis. J.A.M.A. 478, 1944. 4. Cushing, II, Papers Relating to the Pituitary Body, Hypo- thalamus and Parasympathetic Nervous System. Springfield, Illinois, Charles C. Thomas, 1932. 5. Barbour, H, The heat-regulating mechanism of the body. Physiol. Rev. 1; 295, 1921. 6. Hardy, J. D, and Soderstrom, G, F, Heat loss from the nude body and peripheral blood flow at temperatures of 22°C, to 35°C. J. Nutrition. 16: 493, 1938. 7. Palmes, E, D. and Park, C. R. A method of human calorimetry. MDFHL Project No. 55-3, 1 April, 1947. 8. Palmes, E. D. An apparatus and method for the continuous jreasuroraent of evaporative water loss from human subjects, AMRL Project No. 55-1, 28 February, 1947. 9. Palmes, E, D. and Park, C. R, An improved mounting for thermocouples for the measurement of the surfact temperatore of the body, MDFRL Project No, 55-2, 18 March, 1947. TIME (HOURS) FIG I PILOCARPINE 38°C FIG. 2 ATROPINE 38°C