Int. Archly ffir Gewerbepathologie und Gewerbehygiene 20, 311--315 (1963)

Hospital of Nippon Oils & Fats Co., Ltd. Taketoyo Plant and Yoshitoshi Department of Internal Medicine, University of Tokyo School of Medicine

On the influence of nor-adrenaline upon the blood pressure of workers exposed to nitroglycol and the change of the

concentration oi nor-adrenaline and adrenaline in the urine By

KATSUTOSHI IIOTTA~ T a k e t o y o Plant, and RITSUJI YAMADA~ Tokyo

(Received March 29, 1963)

Studies on angina pector is caused b y ni t roglyeol (Ng) poisoning in d y n a m i t e p lan t s have a l r eady been r epor t ed f rom abroad (SY~A~'SKI 1952, BOSTRO~M 1957, t tO~I~G 1957), bu t in J a p a n , this p rob lem has begun to a t t r a c t our a t t en t i on since Augus t 1960. W e per formed wi thou t de lay examina t ions on blood, liver, and c i rcu la tory funct ions of the workers exposed of Ng in a oil and fa t processing plant . And, we ob- t a ined some resul ts b y Hines -Brown ' s cold pressure tes t (}IoTTA and TOKUDA 1962), t h a t is, when those workers underwent the cold stress, the i r systol ic b lood pressures increased gradual ly , and the appearance of the m a x i m u m value of the blood pressure was delayed, wi th abnorma l e levat ion of the dyas to l ie b lood prcssure. These resul ts were found especial ly in workers who suffered f rom so-called Ng angina pectoris .

These resul ts suggested t h a t the vasomotor nervous sys tem has a close re la t ion wi th the Ng poisoning, and this suggest ion led us to do the fo!lowing exper iment . Namely , the p a t t e r n of the rise of the blood pressure of Ng workers was inves t iga ted using nor -adrena l ine N-A (N-A-Test) , where as the i r b lood pressure d id not increase b y the cold stress tes t . And, moreover , we pursued the re la t ion be tween excre t ion of N-A and adrenal ine (Ad) in the ur ine and vasomotor react ions to N-A. The present r epor t describes some resul ts ob ta ined from these experi- ments .

Subjects and methods The N-A test was performed on all the members of the following three groups. Group A. Ng angina patients, 6 workers in all. Group B. 30 workers, sampled at random among the workers in the work-

places where Ng was being handled. Group C. 10 workers, from the work shops where Ng was not handled, sampled

at random. The test was performed as follows. Workers were laid in bed for 30 minutes

for rest. They were injected with 1.0 ml of 0.1% N-A subcutaneously. N-A used for this test was of the same lot. Blood pressures were measured every 5 minutes for 1 hour. In 16 workers (6 of Group A, 5 at random from Group B, 5 ~t random from Group C) amounts of N-A ~nd Ad in the urine, stored for 8 hours of work- time, were determined by Lund's Method (Lwcn I949). This experiment was performed during the period from Aug. 17th to Sept. 10th, 1961.

Int. Arch. GewerbeDath. Gewerbehyg. ]~d. 20 21

312 KATSUTOSHI HOTTA and RITSUJI YAz~IAD.~:"

Results Resul ts are shown in Table 1. First , by N-A inject ion the systolic

as well as dyastolie pressures immedia te ly rose and recovered to the

Table I,

Group

Falue~ of the blood pressure elevated by N-A injection and its duration

Group C (Control group)

~at~ of b~o4 Duration of Blood pressure rise blood p~ssu~

pressure by N-A rise (rain) No. Name Sex Age before the injection Syst. I Dia~t. P. P. Syst. [ Diast. P, P.

1 T.S. ~ 39 126--74 20 4 28 17 2 G.S. ~ 46 102--70 14 16 22 30 3 Y.S. ~ 35 130--76 6 8 20 25 4 S, S. ~ 48 106--70 18 16 23 23 5 U. S, ~ 43 106--70 44 38 35 35 6 T.S. ~ 35 122--80 54 30 27 35

M. T, ~ 24 116--60 20 30 22 20 I .S . ~ 33 124--84 46 26 27 10 H.S. ~ 38 136--90 8 2 17 10 L K. ~ 33 110--66 32 32 22 25 K, E. i ~ 33 124--80 16 20 19 25 Y.W. ~ 48 122--70 40 20 27 30 M.H. ~ 48 110--70 40 20 25 19 H.H. ~ 27 104--58 22 32 25 27 ¥ . t . ~ 29 96--66 18 t4 35 29 K.T. 9 19 106--70 20 20 50 30 Y. A, ~ 20 108--72 42 28 35 ~ 20 H.T. ~ 16 116--70 34 0 26 J 10 K.T. ~ 17 ]08--56 18 12 24 20 T.A. ~ 17 120--70 16 14 24 20 M.S. ~ 27 130--80 46 6 23 10 S.S. ~ 19 124--70 52 20 37 50 l~.M. ~ 26 106--60 32 30 30 25 K . L ~ 28 124--76 46 22 45 40 ~f. A. ~ 35 108--60 42 20 34 45 K.S. ~ 23 134--60 6 36 22 35 K.S. ~ 19 120--64 34 36 55 45 H.T. ~ 28 120--76 30 24 43 40 T.S. ~ 26 108--80 42 16 46 22 ¥ .M. ~ 26 114--70 36 30 25 25 Y.T. ~ 20 114--76 16 18 28 28 I . I . ~ 17 120--76 28 12 32 35 S.H. 2 18 118--80 22 66 32 10 A . ¥ . ~ 17 116--76 16 16 47 50 T.S. ~ 19 118--58 20 32 32 42 K.S. ~ 32 116--70 10 24 14 20

60 45 35 48 45 55 60 46 6O 60

On the influence of nor-adrenaline upon the blood pressure 313

initial lever after the durat ion shown in Table 2. We found tha t the durat ion of the rise of blood pressure by N-A was less in Group A and Group B than in Group C. Stockastic evaluation of these results revealed that , as regards the systolic pressure, t-score was 2.56 between Group C and Group A, it was 2.51 between Group C and Group B, and as regards the dyastolic pressure, t-score was 2.6 between Group C and Group B, tha t is the durat ion of the rise of blood pressure in Group A and Group B was less than Group C and this difference was significant.

Secondly, we observed the differences between the maximum values of the systolic pressure as well as dyastolic pressure before and after the N-A injection. The results are shown in Table 3. As regards the systolic pressure, t-score was 7.0 between Group C and Group A, it was 10.8 between Group C and Group B. As for the dyas- tolie pressure, t was 5.8 in Group C v. Group A, and it was 5.65 in Group C v. Group B. Both are remark- ably high. The conclusion

Table 2. Duration o/blood pressure rise (mean values)

G roupA GroupB Group C m i n rain m i n

Systolic pressure 25.83 30.76 54.5 Dyastolic pressure 27.5 27.2 51.4

Table 3. Rate o] blood pressure rise by N-A injection (mean values)

Group A I Group B ] Group C

Systolic pressure 26.0 28.3 Dyastolie pressure 18.6 21.0 35.6

42.6

Table 4. Excretion o/N-A and Ad in the urine stored/or 8 hours in worktime

Group A

Group B

Group C

No.

1 2 3 4 5 6

mean value

2 4 6 7 9

mean value

1 2 3 4 5

]I lean v a l u e

Sex Age

39 46 35 48 43

$ 35

33 33 48 48 29

N-A in Ad in urine urine (y/Sh) (y/8h)

1.56 0.36 2.32 0.76 0.62 0.55 2.88 0.76 0.74 0.17 2.18 0.67 1.71 0.54

1.15 0.00 1.50 0.27 0.43 0.38 2.O8 0.00 3.02 1.08 1.64 0.34

0.66 0.23 0.12 0.68 0.16 0.37

is tha t the degree of the blood pressure rise caused by N-A injec- t ion is less in Group A and Group B than Group C.

Thirdly, i.e. as to N-A excretion in the urine stored for 8 hours, our results are shown in the Table 4, mean values are 1.71 y/8 h, 1.64 y/8 h and 3.10 y/8 h in Group A, Group B and Group C, respectively. The values of Group C are highest. T-score is 2.61 in Group A v. Group C,

21"

314 KATSUTOSttI HOTTA_ and RITSWI ¥AMADA:

2.73 in Group B v. Group C, i.e. showing the difference significant. Bu t difference of A d excre t ion in the ur ine is not significant.

Discussion F r o m the above resul ts we f ind t h a t bo th the degree of the e levat ion

of the blood pressure and its du ra t ion are less in Group A and Group B t h a n Group C.

We already reported (HoTTA and TOKUDA 1962) that the blood pressure rise by the cold pressure test in workers exposed to Ng was rather little. From these two results, it may be said that the decrease of the sensitivity of peripheral blood vessels to N-A seems to be the most important factor, while EuLE~ (1956) and YOSalVE (1956) say that the hypothalamus and the medullary vasomotor center are also connected with.

I n a word, these results suggest t h a t the homoes ta t i e mechan i sm of b lood pressure in Ng workers is imperfect , i.e. the a da p t a t i on to the blood pressure e levat ion b y N-A is no t sa t i s fac tory . As to N-A excre t ion in the urine, as shown in Table 4, i t seems to suggest t h a t the excre t ion is decreased in Ng workers due to the d is turbance of nervous sys tem b y Ng.

Some clinical investigators (LvFT 1953, TASAKA 1960) reported that the diminu- tion of N-A excretion in the appeared in the case of disturbance in blood pressure homeostatic reflexes and other neural diseases. Especially, TASAXA et al. (1960) reported that if there were some diseased conditions around hypothalamus, rich in catecholamine, and if there were grave disturbances in the high level of autonomic nervous system, there should be naturally some influence on the amount of N-A in the urine, and that, even if the value of N-A or Ad in the urine of these patients was in the normal range, the value was generally apt to be at the lower part. On the other hand, it was said that the subjective symptoms in Ng group and the symptoms and onset of the so-called Ng angina patients were remarkably similar to those of diencephalopathia vascularis (Zo~DsK 1950, 1952, MATUUXA 1961, 1962). This suggests that there is a serious disturbance in hypothalamus. And this may be supported by the fact that Ng is fat soluble and has much affinity to cranial nervous cells.

Hav ing the same idea as STs~I~ (1956) and SAXABE (1961), we s tud ied the influence of Ng on the vasomoto r nervous sys tem a n d central nervous system, and from the resul ts of the excre t ion of N-A in the urine and of the N-A test , we found t h a t the na tu re of Ng-poisoning was a funct ional d i s tu rbance of the centra l nervous system, a n d espe- cial ly of hypo tha l amus , which migh t p l ay the leading pa r t to the onset of symptoms .

Therefore, i~ m a y be though t t h a t the blood pressure rise b y N-A (N-A test) and the excre t ion of N - A in the ur ine should be per formed as a t es t for the p rophy lax i s of Ng-poisoning in workers employed a t the shop where Ng is being handled. F o r inves t iga t ion on the funct ion of h y p o t h a l m u s of Ng workers, the mecholyl tes t was planned, bu t considering danger inva lned in this tes t , we are expect ing to pe r fo rm this tes t careful ly in future. We are also in tending to do the tes t of N-A in the ur ine in more Ng workers.

On the influence of nor-adrenaline upon the blood pressure 315

C o n c l u s i o n s

l . As the resul ts of nor -adrena l ine (N-A) test , bo th the du ra t ion of b lood pressure rise and i ts degree are less in Ni t rog]ycol (Ng) workers t h a n the control group.

2. N - A excre t ion in the ur ine of the Ng group has a t e n d e n c y to be less t h a n the control group.

3. Judg ing f rom the resul ts of the N-A tes t and N - A excre t ion in the urine, i t m a y be said t h a t the d i s tu rbance in the hypo tha ]amus is p lay ing a ma in pa r t of the mechanisms of Ng-poisoning. This d i s tu rbance causes the same s y m p t o m as in d iencepha lopa th ia vaseularis .

4. I t m a y be though t t h a t the N - A tes t and the measu remen t of N-A in the ur ine are useful as a means for the p rophy lax i s of Ng poisoning.

Acknowledgement. We wish to express our gratitude to Prof. Dr. HII~O3~ASA KITA and Dr. HlXOYVI~I SAlSA:BE for their continuous guidance and encouragement throughout this work.

References BosT~6~, G., S. ]~'onss~A~ and G. J o ~ s s o N : Medical examination of workers

engaged in the manufacture of nitroglycerin and ethylen glycol dinitrate in the Swedish explosives industry. Occup. Hyg. Toxicol. 32, 1071 (1957).

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action of nitroglycerine. Amer. J. Med. 39, 910 (1960). ~OTTA, K., and S. TOKUDA: Results of cold-pressure tests on workers exposed to

nitroglyeol. Jap. J. Ind. Health 4, 584--587 (1962) [in Japanese]. LVFT, R., and U. S. V. ETJL~: Two cases of postural hypotension showing a

deficiency in release of nor epinephrine and epinephrine. J. elin. Invest. 32, 1065--1069 (1953).

LU~D, A. : Fluorimetric determination of adrenaline in blood. III . A new sensitive and specific method. Acta pharmacol. (Kbh.) 5, 231--247 (1949).

MATVV~A, S.: Dieneephalopathia vascularis. Jap. reed. J. No 1990, 117 (1961) [in Japanese].

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Japanese]. ST~r~, W. : Uber den Wirkungsmechanismus chronisch inhaIativer Nitroglykol-

einwirkung. Arch. Gewerbepath. Gewerbehyg. 15, 19 (1956). S ~ _ ~ s ~ I , It. : Schwere Gesundheitssch~digungen durch berufliche Nitroglycol-

einwirkung. Arch. Hyg. (Berl.) 136, 139--158 (1952). T~SAKA, S.: On the clinical significant of catecholamine. Seishin Igaku 1~, 2326

(1960) [in Japanese]. ¥os~%v]~, S. : On the abnormal secretion of the adrenaline and nor adrenaline.

Endocrinology and Metabolism 1, 13--39 (1958). ZO~D~K, H. V. : Diencephalopathia vascularis. Sehweiz. Med. Wschr. 80, 957 (1950). - - Diencephalopathia vascularis. Sehweiz. Med. Wschr. 82, 82 (1952).

Dr. KATSIITOS~II HOTTA, Hotta Hospital, Nagaike-cho 1--8, Showa-ku, Nagoya/Japan