physique. insecticides, which are being used increasingly throughout the Interference with sweating would be a major hazard in a climate

Transcription

1 THE EFFECT OF ATROPINE SULPHATE ON MEN EXPOSED TO WARM ENVIRONMENTS. By H. CULLUMBINE and S. MILES. From the Chemical Defence Experimental Establishment, Porton, near Salisbury. (Received for publication 2nd Febrmary 1955) ATROPINE is at present the accepted therapeutic agent in the treatment of poisoning by anticholinesterase substances such as the organic phosphate insecticides, which are being used increasingly throughout the world and particularly in tropical areas. Since the recommended dose of atropine sulphate is or more, it becomes important to appreciate the possible risks of atropine in these large doses under various environmental conditions. Cullumbine, McKee and Creasy [1955] showed that in a temperate climate atropine sulphate can be administered intramuscularly to young adult males without causing distress or significant loss of physical efficiency. In a warm environment, however, since atropine inhibits sweating and increases the heart rate, it might be expected to interfere with the regulation of body temperature. Interference with sweating would be a major hazard in a climate where the maintenance of body temperature depended upon the adequate evaporation of sweat, i.e. in a hot dry climate where the air temperature was above that of the body. In a warm moist climate where air temperature is below body temperature, the high atmospheric moisture content lessens the ability of the body to evaporate sweat, and heat is lost mainly by radiation, convection and conduction; so inhibition of sweating by atropine should be less of a handicap. In the experiments to be described, the effects of doses of atropine sulphate intramuscularly have been assessed in healthy young adult males during the process of acclimatization to two environmental conditions, one hot and dry, the other warm and moist. METHODS Forty male volunteers, aged 18 to 31 years, were used in the tests, the majority being between 18 and 22 years. All were of good physique. 162

2 Atropine Sulphate on Men Exposed to Warm Environments 163 The two environments chosen were: (i) Hot and dry Dry bulb, 9 -l12 F. Wet bulb, F. Mean relative humidity, 36 per cent. (ii) Warm and moist Dry bulb, 9 F. Wet bulb, 85 F. Mean relative humidity, 81 per cent. The climatic chamber used was ventilated by an exhaust fan set to give a manometer reading of 18 to 2 cu. ft. per min. Mean air movement in the area where the men were seated was measured with a kata thermometer and found to be 2 ft./min., giving basic effective temperatures for the two environments of 92 and 86 F. A kata thermometer held by an exercising man, however, gave a reading for air movement of 6 ft./min., for which the respective basic effective temperatures would be 9 and 85 F. (This difference is not great and does not affect the conclusions drawn from the results.) Wet and dry temperature recordings were taken every 15 min. with an Assmann psychrometer, and the chamber environment was thermostatically controlled and did not at any time vary from the chosen mean by more than ±2 F. Twenty men were exposed to each environment on days, and men of these received atropine on the 5th and th days. Before entering the chamber the men sat and their blood pressures were measured. They then changed into plimsolls and shorts, entered the chamber and were weighed nude. Expired air was collected whilst sitting for 5 min., after which pulse rates and rectal temperatures were recorded standing. During each forenoon four exercise periods, consisting of stepping -on and off a 15-inch stool 12 times per min. for 3 min., were completed with rest periods of 25 min. between the 1st and 2nd and 2nd and 3rd work periods and 4 min. between the 3rd and 4th. Pulse rates and rectal temperatures were taken before and after each work period. Samples of expired air were collected during the 3rd work period and after completion of the 4th. A second blood pressure reading was made in the middle of the 4-min. rest period, and sweat was collected in a plastic arm bag throughout the final work period. Before leaving the chamber and 4 hours after the first weighing the men were again weighed nude. The men were in the chamber for the same 4 hours each day for ten consecutive days and, to facilitate continuous urine collection, from 14 hours on the day before first entering the chamber to 14 hours on the final day they were accommodated in a hospital ward.

3 164 Cullumbine and Miles Venous blood samples were taken before and after exposure on days 1, 3, 5, 8 and. Analysis of sweat chlorides, urine chlorides and plasma chlorides were carried out by the methods of King [1947]; total urinary 17-ketosteroids by that of Drekter [1952] and eosinophil counts by that of Randolph [1944]. RESULTS The results of the various investigations will be presented separately. For simplicity, the changes occurring on the 1st, 5th and th days only will be given, the last two of these being the days on which half the men in each environment received atropine. Day to day records, however, were taken and are available. (i) WORK PERFORMANCE (Table I) The energy expenditure during actual work was at a mean rate of 182 cal/m2/hr., and the mean overall expenditure during work and rest for the four hours was 118 cal/m2/hr. In the HOT DRY environment, on the 1st day the men were not quite able to complete a full work programme, but those who did not receive atropine did so on the 5th and th days. Those who received atropine on the 5th day attained a mean work performance of 83 per cent of the 1st work period, but only 12, 17 and 31 per cent respectively of the remaining three periods. The first period, immediately following injection, would be concluded before the full effects of the drug were felt, and the waning of its influence would allow of better performance during the final work period. On the th day, those who received atropine were able to do more work, the mean performances being 93 per cent for the 1st period and 25, 42 and 53 per cent respectively for the other periods. Thus the ability to perform work in a hot dry environment is more severely impaired by atropine on the 5th than on the th day. This may be due to acclimatization being more complete on the th than on the 5th day. In the WARM MOIST climate, on the 1st day all men completed the four work periods, and similarly on the 5th and th days full work performance was achieved by men not receiving atropine. When atropine was given, the work performances were much better than in the hot dry conditions. On the 5th day all completed the first work period, and the mean performances for the remaining three periods were 88, 85 and 68 per cent. Furthermore, there was a very similar performance after atropine on the th day, the figures for the four

4 Atropine Sulphate on Men Exposed to Warm Environments 165 work periods being 97, 78, 69 and 9 per cent, an almost identical overall performance on the two days. In the warm moist environment, therefore, atropine has similar effects on work performance on the 5th and th days, which may indicate that there is little, if any, appreciable change in acclimatization between these two days. TABLE I.-EFFECT OF I.M. INJECTION OF 2 MG. ATROPINE SULPHATE ON MEAN PER CENT WORK PERFORMANCE, PuLSE RATES AND RECTAL TEMPERATURES OF MEN WORKING IN HOT DRY AND WARM MOIST ENVIRONMENTS (4 HouRs' EXPOSuRE DAILY FOR DAYS). Per cent work performance (i) Hot and dry Day 1., 5,, 5,,,, (ii) Warm and moist Day 1,, 5,, 5,,,, Pulse rate per m'in. (i) Hot and dry Day 1 to 5 (ii) Warm and moist Day 1,, 5,, 5,,,, Rectal temperature 'F. (i) Hot and dry Day 1,, 5,, 5 (ii) Warm and moist Day 1,, 5,,5 VP No. of Dose of 1st work men atropine period ',, 24 mg nd work 3rd work 4th work period period period Before After Before After Before After Before After *

5 166 Cullumbine and Miles (ii) CHANGES IN PULSE RATE (Table I) In the HOT DRY environment, on the 1st day the mean pulse rates after work periods ranged from 15 to 153/min., falling with rest to 135/min. The post-work rates were less, 125 to 135/min., on the 5th day in the unatropinized men with a level of 112 to 115/min. at rest. Even lower rates, 115 to 129 after work and 3 to 1 after rest, occurred on the th day, showing improvement beyond the 5th day. When atropine was given in the hot dry atmosphere, a mean maximum pulse rate of 165/min. occurred after the 1st work period of the 5th day, falling with rest to 142/min. This fall continued through the second work period to 128/min. The next rest period saw a further fall to 125, after which the rates for the remaining half of the exposure period followed closely those of the unatropinized men for the same day. Thus during the first 2 hours of exposure the effect of atropine on pulse rate overshadowed that of effort, after which its influence was less than that of the work. On the th day in this atmosphere atropine produced a very similar series of pulse rates but at the same time more work was being performed. In the WARM MOIST environment, the mean pulse rates on the 1st day ranged only between 137 and 143/min. after the exercise periods and between 118 and 119 after rest-figures which were about beats/min. below the corresponding figures in the hot dry environment. On the 5th day the mean pulse rates after work in unatropinized men were 6-116/min. after work and 95-5 with rest. On the th day the same men showed little change, the work and rest ranges being and 96-4/min., showing that in this environment there is no improvement in pulse rate beyond the 5th day. When atropine was given in the warm moist environment, the pulse rate on the 5th day rose after the first work period to 168/min. and fell with rest to 146/min. (The immediate effect of atropine, therefore, on the pulse rate was the same in both environments in spite of the fact that more work was done in the warm moist climate.) After the second work period with atropine in the warm moist environment the pulse rate rose to 154/min. Here considerably more work (88 per cent) was done than in the hot dry climate (12 per cent), where the pulse rate at this stage fell to 125/min. Higher rates (with more work) were similarly maintained through subsequent periods. After atropine on the th day there was a mean pulse rate of 155/min. at the end of the 1st work period. (A slightly smaller figure than on day 5 as a little less work was performed.) With rest the rate fell to 144/min., and thereafter maintained a

6 Atropine Sulphate on Men Exposed to Warm Environments 167 course following closely the rates of the 5th day. Similar work rates were performed on both days. Therefore, the post-exercise pulse rates show a similar trend following atropine on the 5th and th days in the hot dry environment, although approximately twice the amount of work was done on the th day. This is further evidence that the process of acclimatization in this environment is less easily disturbed by atropine on the th day. Also in the warm moist environment the pulse rates followed similar courses after atropine on the 5th and th days, and here, as seen, the work done was substantially the same on the two days. Again this suggests a similar degree of acclimatization on the two days in this environment. (iii) CHANGES IN RECTAL TEMPERATURE (Table I) In the HOT DRY environment, on the 1st day the 1st exercise period raised the mean rectal temperature of all the men to 1.5 F., and the following three work periods resulted in temperatures of 2-2, 2- and 1.6 F. respectively. The temperatures recorded on completion of rest periods were between 1. and 1.5 F. On the 5th day, the men without atropine produced mean post-work temperatures of -7 F. and after rest - F. The corresponding rectal temperatures for these men on the th day were.3 and 99.7 F., a continued improvement beyond the 5th day. When atropine was given in this environment on the 5th day, the mean rectal temperature after the 1st work period rose to 1-4 F., continued rising through the following rest to 2. F., and remained at this level throughout the 2nd work period, falling with further rest to 1-7 F. This fall continued through the 3rd work period to 1-2 F. and the long rest to.8 F., remaining at this level through the final work period. On the th day following atropine the rise after the 1st work period was less, i.e. to.6 F., and similarly continued through rest to 1.3 F. Thereafter it gradually fell to 99.6 F. at the end of the long rest period, with a small final rise to 99.9 F. after the last work period. Thus tcmperature changes also show that in this environment significant acclimatization is still occurring after the 5th day. In the WARM MOIST climate the mean rectal temperature after 3 min. exercise on the 1st day was.9 F. and after subsequent exercise periods 1.3, 1-2' and 1. F. The temperatures in the three intermediate rest periods were -2,.3 and. F. On the 5th day in the unatropinized men the initial rise after work was to 99.6 F., subsequent post-work rectal temperatures being., - and 99.9 F. The mean rectal temperatures after the rest periods on this day were 99.2, 99.4 and 99. F. On the th day a similar

7 168 Cullumbine and Miles picture resulted for the same men, the post-exercise temperatures ranging from 99.8 to. F. and those with rest from 99- to 99.2 F. This was further indication of the small difference between the acclimatization achieved on the 5th and th days in the environment. With atropine on the 5th day a rise to -8 occurred after the 1st work period and to 1.9, 1-3 and -3 F. following subsequent work periods, whilst the post-rest temperatures were.7, 1. and.1' F. On the th day the four post-work temperatures recorded for these men were.,.6,.4 and.6 F., with intermediate resting temperatures of 99.7, -3 and 99.6 F. In BOTH environments the maximum temperature following atropine was reached in 1-1 hours after injection, whereas the maximum pulse rate occurred in 3 min. The increase in body temperature following atropine is presumably due to inhibition of sweating and, therefore, some delay in reaching a maximum effect would be expected. In both environments the rise in rectal temperature following atropine was less on the th day than the 5th. This occurred in the hot dry climate in spite of the fact that more work was done on the latter day, i.e. acclimatization in this environment was less complete on the 5th day than the th. It is also noteworthy that whereas in both environments pulse rate was affected to the same extent by atropine, the rise in temperature was more in the hot dry climate, illustrating the greater dependence on sweating for maintenance of body temperature in this environment. (iv) CHANGES IN BLOOD PRESSURE (Table II) The systolic blood pressure measured sitting was, under both conditions and on all days, lower after 3 hours' exposure than before entry into the chamber. Without atropine there was little variation from the mean fall of 12-2 mm. Hg. Atropine produced a greater fall, the readings for the 5th and th days in the hot dry climate being 92 and 96 mm. Hg. and in the warm moist climate 86 and 84 mm. Hg. This further fall produced by atropine may be due to an increase in vasodilatation over and above that required to meet the needs of heat loss. A marked general flushing of the skin was indeed seen in all men following the injection of atropine. Diastolic blood pressures showed a similar relative fall, except that in the warm moist environment the atropine did not accentuate the fall produced by the environment. (V) SWEAT Loss (Table II) Loss of nude weight over each 4-hour period of exposure, after correction for any water drunk or urine passed, was taken as a measure of 4-hourly sweating rate.

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9 17 Cullumbine and Miles In the HOT DRY environment without atropine the mean sweat loss increased from 2148 g. on the 1st day to 2378 g. on the 5th, with a similar figure of 2322 g. on the th. Atropine reduced the sweat loss to 6 g. on the 5th day and to 9 g. on the th, although much more work was done on the latter day. In the WARM MOIST environment the mean sweat losses in unatropinized men remained much the same throughout, being 1347, 1343 and 1329 g. on the 1st, 5th and th days. Atropine here reduced the sweat loss on day 5 to 686 g. and on day to 627 g. for similar amounts of work. It was observed that atropine stopped visible sweating for a part only of the 4-hour exposure period. In the hot dry climate visible sweating did not occur until 21-3 hours after injection, but in the warm moist climate sweating was seen up to 2 min. after injection, from which time the skin remained dry for a further 2 hours. (Vi) SWEAT CHLORIDE CONTENT (Table II) On those days when atropine was given it was not possible to collect sufficient sweat for analysis. Apart from this effect of atropine, there was in both environments a decrease in the mean sweat chloride content with acclimatization. (Apart from any possible influence due to acclimatization, a fall in the chloride concentration of sweat is to be expected in arm-bag collections with repeated exposure.) In the hot dry climate this fall was from 11- mg. on the 1st day to 9 mg. NaCl/ml. on the th day, and in the warm moist climate over the same period from * to 8*4 mg. NaCl/ml. (Vii) URINE CHLORIDE CONTENT (Table II) Without atropine the output of urinary chloride increased from 4-65 g. NaCl/24 hrs. on the 1st day to 8-58 on the 9th day in the hot dry environment, and from 5 9 to 11. g. over the same period in the warm moist environment. With atropine on the 5th day in the hot dry environment there was no appreciable difference, but in the warm moist environment there was some decrease. (viii) EXCRETION OF TOTAL URINARY 17-KETOSTEROIDS (Table II) Estimations of total 17-ketosteroids were made on all urine excreted during the ten-day period. Interpretation of the results is made difficult by the lack of specificity of the method used, the uncertainty of origin of the ketosteroids, and the possibility of reabsorption, especially when less than the normal amount of urine is being passed.

10 Atropine Sulphate on Men Exposed to Warm Environments 171 No day-to-day changes in either series were observed in unatropinized men, but a higher level (mean 13x/24 hrs.) was maintained in the warm moist environment than in the hot dry (mean 9*7 mg./24 hrs.). The total volume of urine passed in 24 hours was on each occasion considerably reduced (by approximately 3 per cent) by the injection of atropine, and there was a similar reduction in the amount of 17-ketosteroids excreted on day 5 in the warm moist climate (8./24 hrs.). This adds to the significance of the increase which occurs on day 5 (11.9 mg./24 hrs.) in the hot dry climate in spite of reduction in urine output, suggesting that in this environment the atropine injection produces a greater stress. This is a reasonable assumption, as it is in the hot dry climate that sweating is the essential mechanism of cooling and its inhibition, therefore, would be a greater stress. (ix) BLOOD CHANGES (Table II) (a) Total Eosinophil Counts.-As there was a variation in mean counts from 155 to 238 per c.mm. in the pre-exposure sample and from 131 to 211 per c.mm. following exposure with no pattern of day-to-day change, it was impossible to attach any significance to the results. (b) Packed Cell Volume.-Acclimatization to the HOT DRY environment was accompanied by a slight fall in the daily P.C.V. values ( per cent). Each daily exposure, however, produced an increase in P.C.V. in the earlier days (e.g. to 47-5 per cent on the 1st day), and this daily increase gradually lessened so that no change was occurring on the th day. With atropine there was no change in P.C.V. during exposure on either day. The WARM MOIST climate did not produce appreciable changes in P.C.V. except following atropine, when on both days there was a8 fall. The reduction in sweating due to atropine would itself tend to lessen the development of haemoconcentration due to environment, and atropine in a temperate environment is known to produce a heemodilation [Walker, Parker and Hunter, 1955]. (c) Plasma Chloride.-On no occasion was any change seen in plasma, chloride concentration. Nor had atropine any effect. Salt depletion, therefore, in these experiments never reached a stage which would alter the plasma level. (x) RESPIRATORY EXCHANG1E (Table II) On the first day in the hot dry environment the resting minute volume was greater after 4 hours' exposure to heat. On the 5th day this increase was 3*3 1. and on the th day only Much VOL. XLI, NO

11 172 Cullumbine and Miles smaller increases were found in the warm moist environment, the three corresponding figures being 2-62, *77 and Thus there was with exposure to heat an increase in ventilation. In the hot dry climate this increase was 55 per cent on the first day, for which there was only a 33 per cent increase in oxygen consumption. Similar relationships between minute volume and oxygen intake were found throughout. During work in both environments there was little change in minute volume from day to day; so it would appear that only at rest is the minute volume increased as a means of improving heat loss in the early stages of acclimatization. (At work it is already high.) When acclimatization is established this accessory mechanism is of less importance. With atropine in the hot dry climate there is a much smaller increase in resting minute volume with exposure on the 5th day, but on the th day, and on both days in the warm moist environment, there is an actual decrease in minute volume. At the time of the second resting sample, however, the acute effect of atropine had passed off and a state of lethargy had developed, which may well account for this decrease in respiratory effort. (Xi) SKIN TEMPERATURE (fig. 1) It was not possible to record skin temperatures of the 4 men used in these hot-chamber trials, but an opportunity arose in Nigeria which made it possible to investigate the effect of similar injections of atropine in 4 locally acclimatized West African soldiers under controlled conditions. The mean normal environment of these men was 85 F., with 81 per cent relative humidity. A climatic chamber at 9 F. and 86 per cent R.H. was available, and in this the 4 men completed six 15-min. work periods in 41 hours daily for 5 days, with a mean overall energy expenditure rate of 155 cal/m2/hr-. On each of the last four days one man received an intramuscular injection of atropine sulphate prior to starting the first exercise period. Skin temperature measurements were taken from forehead, cheek, chest and hand before injection, on completion of the 2nd, 4th and 5th work periods, and in the middle of an hour's rest between the 4th and 5th work periods. In the unatropinized men, temperatures of forehead, cheek and chest rose with work to between 97.5 and 98.5 F., whilst that of the hand did not exceed 96- F. When atropine was given, the highest temperature following work occurred in the chest, reaching.8 F. Forehead and cheek temperatures were a little less. The most striking difference was seen in the skin temperature of the hand, which reached 99 F., its course following those of the other sites.

12 Atropine Sulphate on Men Exposed to Warm Environments NO ATROPINE. --11= '9. OF IoIr I HOURS I 1I. ATROPINE 2 mg ~ *F ; HOURS SKIN TEMPERATURES FOREHEAD CHEEK CHEST HAND * X X 111. FIG. 1.-Effects on skin temperatures of I.M. injection of atropine sulphate on men completing six 15-mmn. work periods in 4 hours at 9 F. and 86 per cent R.H. (Work periods M.)

13 174 Cullumbine and Miles (Xii) CONSIDERATION OF THE INDIVIDUAL SUBJECT Considerable individual differences in reaction to the hot dry environment were found, whereas in the warm moist environment there was little variation from the general mean. These differences in the hot dry environment were high on the 1st day in particular, but declined considerably as acclimatization progressed, and were very much less marked on the th day. Two subjects may be taken as an example of this difference in reaction. These two men both completed per cent work on the first morning, during which the rectal temperature of the first reached 3.5 F., whilst the other's did not exceed 1.4 F. Each had a similar pulse rate, but the first (with the higher temperature) had a low systolic blood pressure of 84 mm. Hg as compared with 12 mm. Hg in the second. Both diastolic pressures were 6 mm. Hg, all the readings being taken 3 hours after entry into the chamber. Sweating rates, which differed greatly, may have been responsible for these results, as the man whose temperature rose to 3.5 F. lost only 1973 g. in the 4 hours as compared with his companion's 2463 g. The differences in the reactions of the two men lessened with the development of acclimatization, and on the th day the highest temperature reached by the first man was.7 F. and the second 99.7 F. Blood pressures were 9/55 and 88/58 mm. Hg respectively, and the sweating rates 2129 and 2559 g./4 hours. Thus in a random group of men exposed to a hot dry environment, some underwent a greater degree of acclimatization than others to reach a fairly uniform level, or, in other words, quite apart from any previous climatic exposure, some individuals are already more adapted to heat than others. (Xiii) SUBJECTIVE EFFECTS OF ENVIRONMENT AND ATROPINE In both environments the first two days were the most uncomfortable, but of the two climates the men preferred the hot dry one, in which they remained active and alert. By contrast in the warm moist climate, with the dripping state of walls and papers and the discomfort of unevaporated sweat, there was a weariness and lack of vitality. Without atropine there were few complaints in either environment, and these occurred on the 1st or 2nd day. In the 2 men exposed to the hot dry climate there were 5 complaints of nausea, 5 of pain in calf muscles and 1 of severe headache, whereas in the same number of men in the warm moist climate, 5 complained of dizziness, 6 of nausea and 4 of severe headache.

14 Atropine Sulphate on Men Exposed to Warm Environments 175 Following atropine all men on both days in each environment had headache, dizziness, flushing of the face and neck, and a dry mouth. Very much greater distress, however, was caused by the atropine on the 5th day in the hot dry environment. Of the men injected all showed restlessness, irritability and some degree of inco-ordination. Six showed circulatory collapse, and 3 of these fainted. Nine had nausea, and 3 complained of tingling of the fingers. The restlessness was particularly marked, and men lay spread-eagled on the floor, constantly changing position. The feeling of heat was intense even when body temperature was not excessive. The symptoms were not due to hyperpyrexia, as they occurred at body temperatures at which on previous days a full work routine had been completed. Nor were they due to a cerebral anmemia from the circulatory collapse, as they occurred whether the men were upright or horizontal. The effect would seem, therefore, to be due to the influence of atropine on the higher centres of the nervous system. The period of irritability lasted 1-1 hours, giving place to exhaustion and sleep from which the men were aroused with difficulty for the routine investigations. Consequently, the second and third work periods were rarely attempted, though good performances were possible in the first period before the atropine was fully effective and in the last when the effect was wearing off. Though these symptoms also occurred on the th day, they were very much less severe and never incapacitating. In the warm moist climate there were few additional complaints and a good work performance was possible on both days. DISCUSSION In these experiments the men were subjected to two stresses, one of climate and one of atropine, both of which made the completion of the work routine more difficult. Body temperature, pulse rate and sweating rate are each influenced by the environment, but they are also affected by the amount of work completed. Therefore, a more accurate evaluation of the changes in these variables will be obtained if they are related to the work performance. Simple indices have been calculated by dividing the mean post-exercise rectal temperatures and pulse rates and the mean 4-hour sweat loss for each daily period by the percentage of work performed (Table III). The effect of climate alone shows that the temperature-work and pulse-work indices fall from the 1st to th days, and to a greater extent in the hot dry environment. In the hot dry climate, although much of the fall occurs in the first 5 days it does continue between the 5th and th days, whereas in the warm moist climate after the initial fall there is no further change between the 5th and th days. The increase

15 176 Cullumbine and Miles in sweating with acclimatization in the hot dry climate is also shown by an increase in the sweat-work index. The effects of atropine are well shown by the changes in the indices. In the hot dry climate the temperature-work indices are increased on day 5 from 1-1 to and on day from 1-3 to 1-897, and the pulse-work indices on the two days from 1-3 to 3-92 and 1-22 to The sweat-work index is increased from to on the 5th day, but decreases on the th from 5-85 to TABLE III.-EFFECT OF INJECTION OF 2 MG. ATROPINE SULPHATE (I.M.), AND EXPOSURE TO HOT AND DRY AND WARM AND MOIST CLIMATES ON RELATION BETWEEN MEAN PER CENT WORK PERFORMANCE AND MEAN POST-EXERCISE, RECTAL TEMPERATURE, PULSE RATE AND HOURLY SWEAT RATES (4 HOURS' EXPOSURE FOR DAYS) No. of Atropine Temperature-Work Pulse-work Sweat-Work men dosage index index index Hot and dry- Day ,, Warm and moist- Day ,, In the warm moist climate atropine increases temperature-work indices from -999 to 1-18 on day 5 and -999 to on day, and the pulse-work indices from 1-1 to 1-8 and 1- to 1-75 on the two days respectively. Sweat-work indices are decreased from to 2-2 on day 5 and from to on day. From these changes and also from a study of day-to-day changes it would appear that in the hot dry environment acclimatization takes place rapidly within the first 48 hours but continues between the 5th and th days and possibly beyond. In the warm moist climate a different pattern is observed. There is a marked, though less extensive, change within the first 5 days, and any further change which may take place is so gradual as to be insignificant in the period between the 5th and th days. This is also illustrated by the response to atropine, when in the hot dry environment the temperature-work and pulse-work indices show rises on both days but a much greater rise on the 5th than the th, whilst in the warm moist climate the increases on the two days are virtually the same. The sweat-work index following atropine in

16 Atropine Sulphate on Men Exposed to Warm Environments 177 the hot dry climate rises on the 5th but falls on the th, due largely to little work being done on the former day for the same decrease in sweating, whilst in the warm moist climate, where approximately the same work is done on both days, there is on each a similar fall. The effect of atropine is further shown by the changes which occur in the blood pressure. In both environments there is a demand for an increase in peripheral circulation. In the hot dry climate it is needed to provide fluid for sweat production, and in the warm moist climate to facilitate heat loss by radiation and convection. Thus in each environment there is a fall in systolic and diastolic pressure with each daily period of exposure, and also a lesser fall in pre-exposure measurements from the 1st to th days with the progress of acclimatization. With atropine there is in both environments a further fall in systolic pressure, which is more marked in the warm moist environment. The diastolic pressure falls only in the hot dry climate. This suggests that in the hot dry climate there is a decrease in both peripheral resistance and cardiac output, and in the warm moist climate a decrease in the latter only. Atropine is known to have a direct vasodilatory effect on the walls of the blood vessels themselves [Hamet, 1936]. In the warm moist climate, where peripheral vessels are likely to be more dilated to meet the need for heat loss by radiation and convection, further lowering in peripheral resistance is unlikely, but decreased cardiac filling due to the excessive heart rate and possibly to relaxation of the great veins, may occur with consequent fall in cardiac output. In the hot dry climate where peripheral vasodilation is less essential for heat loss atropine may well increase it, thus giving a further fall in peripheral resistance. It was also shown that following atropine the skin temperature at all sites rose to a higher level. The hand skin temperature, however, which was little affected by the environment, rose considerably after atropine, an indication of a more general vasodilation caused by the drug. The excretion of total urinary 1 7-ketosteroids was consistently greater in the warm moist environment, and it was in this environment that a smaller degree of acclimatization was achieved in the -day period and the subjects experienced a greater degree of mental and physical exhaustion. The added stress of atropine in the hot dry climate was also reflected by an increase in ketosteroid excretion in the 24 hours following injection. Little information was obtained from estimations of blood eosinophils and plasma chloride, but changes in packed cell volume indicated a day-to-day dilution of blood with acclimatization and a temporary concentration during the actual exposure period in the earlier days. In considering heat loss from evaporation, note must be taken of insensible perspiration and evaporation from the lungs and air passages.

17 178 Cullumbine and Miles Of these the former, being constant and small, will not be discussed, but evaporation from the lungs will vary with respiratory exchange and may be considerable. The volumes of water lost from the lungs have been calculated for the two environments. In the hot dry environment the mean loss per man is -23 g. for every litre of expired air and -218 g. in the warm moist environment. The mean minute volumes for men at work and at rest in the hot dry climate are and respectively, and in the warm moist climate 21P9 1. and From these figures the calculated mean water loss from the lungs in 4 hours' exposure to the hot dry environment would be 98 g. and to the warm moist environment 81 g. These amounts may therefore account for 5 to per cent of the total evaporative heat loss, and thus must be regarded as an active accessory factor in the heat-controlling mechanism of the body and of possible importance where atropine has reduced actual sweating. The impact of atropine on acclimatization produced increased circulatory embarrassment with higher pulse rate and further vasodilation, and a limitation of sweating. The effects are most severely felt in the hot dry climate by incompletely acclimatized men. In addition, the production of cerebral irritation adds greatly to the discomfort, and this, together with circulatory collapse, would produce casualties before any danger from hyperpyrexia occurred. In fact, with the dose as used these symptoms pass, and the heat-controlling mechanism regains its efficiency before body temperature rises to a dangerous level. When day-to-day changes are studied, atropine would seem to reverse the progress of acclimatization, so that men receiving the injection on the 5th day react to the environment in a similar way to unatropinized men on the 1st day, and those having injection on the th day are comparable with untreated men on the 2nd day of exposure. Two major conclusions arise concerning the use of atropine in warm climates. These are: (i) In a hot dry environment an injection of atropine, besides inhibiting sweating, produces marked circulatory disturbance and some degree of cerebral irritation, which in an unacclimatized man would be severe with inevitable collapse. Such would develop before a risk of hyperpyrexia occurred, and the effects of the drug would pass off before this danger became irreversible. In an acclimatized man the adverse effects of atropine would be greatly lessened. (ii) A similar injection of atropine in a warm moist climate would produce only slight diminution of general efficiency and no great hazard would exist.

18 Atropine Sulphate on Men Exposed to Warm Environments 179 SUMMARY 1. The process of acclimatization to hot dry (1 F., 36 per cent R.H.) and warm moist (9 F., 81 per cent R.H.) environments have been studied using 4 male volunteers, and the effects of I.M. injection of atropine sulphate on the 5th and th days of exposure assessed. 2. In both environments acclimatization consisted of a readjustment of cardiovascular balance, an increase in sweat loss (hot and dry only), a decrease in sweat chloride content and an increase in blood volume. 3. Atropine increased circulatory embarrassment by raising the pulse rate and by general vasodilation, and added to the climatic stress by limitation of sweating. In an unacclimatized or partially acclimatized individual in a hot dry environment, circulatory failure and cerebral irritation would be likely to produce casualties before failure of the heat-controlling mechanism could develop. 4. Subjective and individual effects of both heat and atropine are discussed. REFERENCES CULLTuMBINE, H., MCKEE, W. H. E. and CREASEY, N. H. (1955). Quart. J. exp. Phy8iol. 4, 39. DREKTER, I. J. (1952). J. clin. Endocrinol. and Metab. 12, 55. HAMET, R. (1936). C.R. Soc. Biol. Pari8, 122, 42. KING, E. J. (1947). Microanalysis in Medical Biochemistry. Churchill. RANDOLPH, T. G. (1944). J. Allergy. 15, 89. WALuKER, E. H., PARKER, J. M. and HUNTER, J. (1955). Canad. J. Biochem. Phy8iol. 33, 3, 256.