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THE IN-VITRO DEIODINATION OF THYROXINE AND TRIIODOTHYRONINE
368 thick-walled cyst surrounded by a thin layer of tissue. As it was difficult to mobilise, the capsule was incised and a large stone shelled out. The cavity was obliterated from the bottom and the visceral peritoneum repaired. The lesser sac was closed after inspection of the pancreas, which revealed no other stones or other macroscopic abnormality. The gall-bladder, bile-ducts, stomach, and duodenum all appeared normal. The abdomen was closed in the usual manner in layers, but without drainage. The stone (fig. 2) was ovoid, regular in outline, heavy, and hard, with a slightly roughened surface. It measured 2-5 X 2-2 in. It, was perhaps hardly surprising that a man of 59, after open ether anaesthesia, should develop a severe cough ; and 43 hours after operation he was found to have a " burst abdomen " with two coils of small intestine prolapsed between stretched skin clips. These were replaced under minimal basal narcosis and the wound closed by Hamilton Bailey’s method. Most of the original 20-day chromic-gut sutures had been digested and a few " spots " of fat necrosis were seen in the omentum. Recovery was stormy, with periods of obstinate hiccup and vomiting. On Nov. 8, 18 days after the original operation, a tense mass was detected beneath the left rectus muscle lateral to the abdominal wound. This was explored under local anaesthesia and about 600 ml. of yellow thinly purulent fluid was Qvacuated. This was clearly a collection in the lesser sac, a so-called false pancreatic cyst. No organism was seen in, or cultured from, this fluid. The tube was finally removed on Nov. 20, and the patient was discharged from hospital on Dec. 7. free in
Preliminary
a
pancreatic
Comment
Diagnosis in this case was confused only by the supposed rarity of large solitary stones arising from the pancreas. In fact the radiological evidence could fit but one condition-precisely that found at operation. Marshall (1938) points out that " the most important means of arriving at a diagnosis [of pancreatic stone] is a plain radiograph of the upper abdomen. Routine study of the gastro-intestinal tract with barium may hide the stones." In reviewing 36,000 consecutive necropsies Edmondson et al. (1950) found pancreatic calculi in 26 instances, in 6 of which they were solitary. Eliason and Welty (1948) collected 66 cases in which pancreatic stones were found at operation, and 6 were solitary. Lionello et al. in 1944 found 232 recorded cases of all types of pancreatic stone but others have since been reported from France (Cornet 1949, Bergeret 1952), Morocco, India, Brazil, and Finland. All these were multiple, and the only case of solitary stone I have found reported since 1946 was diagnosed by radiography and unconfirmed by operation or necropsy (Sarles et al. 1950). The largest solitary stone which I have seen mentioned was described by Shupman (quoted by Marshall 1938). Its size was 2-5 x 0-5 in. Most authors seem to agree that single stones arise from the pancreatic ducts and in their pathology resemble salivary calculi. No such agreement is found with regard to the multiple stones, which have been explained in various ways. In the management of my case it was a serious mistake, at the original operation, not to drain the region of interference in the pancreas. Evidently some pancreatic enzyme was released into both lesser and greater sacs when the tail of the pancreas was incised to remove the stone. This was, I think, the primary cause of the " burst abdomen," though the post-anaesthetic cough was an essential factor. Drainage would also have prevented the abscess in the lesser sac. I of
am
indebted to
Papua
the Director of Public Health, Territory and New Guinea, for permission to publish this case.
REFERENCES Bergeret, A. (1952) Arch. Mal. Appar. dig. 41, 9, 137. Cornet, A. (1949) Sem. Hôp. Paris, 25, 3054. Edmondson, H. A., Bullock, W. K., Mehl, J. W. (1950) Amer. J. Path. 26, 37. Eliason, E. L., Welty, R. F. (1948) Ann. Surg. 127, 150. Lionello, J., Ficarra, B. J., Ryan, N. H. (1944) Arch. Surg. 48, 137. Marshall, W. A. (1938) Radiology, 31, 562. Sarles, R., Sarles, H., Mathieu, H. (1950) Arch. Mal. Appar. dig.
39, 1170.
Communications
THE IN-VITRO DEIODINATION OF THYROXINE AND TRIIODOTHYRONINE DEIODINATION processes in the body have recently assumed importance in relation to thyroid function, as the result of the discovery of triiodothyronine 12 which appears to be the active form of the thyroid hormone. (This subject was reviewed by Maclagan and Wilkinson.3) While the deiodination of thyroxine has been amply demonstrated in intact animals, no unequivocal reports of in-vitro deiodination have appeared, although the probable conversion of thyroxine to triiodothyronine in rat-kidney slices has been announced by Albright, Larson, and Tust.4We have studied the production of iodide from thyroxine in homogenates from a number of rat tissues, employing both radioactive and non-radioactive thyroxine as substrate, and have been able to demonstrate active deiodination by both methods. After incubation the homogenates were precipitated with 5% trichloroacetic acid, and the iodide in the filtrate was estimated either by electrometric titration5 or by counting in the liquid Creiger-Muller counter of Veall.6 In the non-radioactive systems the level of substrate concentration used was 5 mg. of L-thyroxine per gramme of liver, and up to 20% the could be
of
thyroxine
TABLE I—DEIODINATION OF L-THYROXINE
(5 M&.)
HOMOGENATE AT DIFFERENT REACTIONS IN
Buffer
i
I I I
I
3.5
µg. per g.
liver
I
3-0
55
M./10
citrate
!
M/10
citrate
!
7-0
i! I
9-5
I
38°C
% total substrate iodine
!
2v 2.5 19.8 16-0 0-6 0-6
510 20 20
M/10 citrate
40 50 348 368 525 520 190 185
M/10 glycine M/10 glycine
10-5
I
65 5 80 630
M/10 citrate
9-0
HOURS AT
Iodide liberated
,
PH n
BY RAT-LIVER
18
M/10 glycine
I
1-3 1-6 10.9 116 16-5 163 6-0
,
5-8 _ _
deiodinated in 18 hours at pH 35 or at pH 9.5. A typical is shown in table I. This liver system also attacked L-triiodothyronine under the same conditions, giving 7% deiodination at pH 9.5 but being without effect at pH 3-5. It was inhibited by exclusion of air and by cyanide but not by citrate nor by anti-thyroxine substances. In the radioactive systems (4 !1-g. of 131I-L-thyroxine per g. of tissue) up to 80% of deiodination was recorded in 3 hours at pH 6-0 as shown in table 11. This reaction was most prominent in liver homogenates but could also be demonstrated in homogenates from brain, kidney, muscle, spleen, adrenal, thyroid, and intestinal mucosa. In the case of liver it was inhibited not only by exclusion of air and by cyanide but also by citrate and by two typical anti-thyroxine substances (n-butyl 4-hydroxy-3: 5-diiodobenzoate (B.H.D.B.) and
experiment
&bgr;-hydroxyethyl 4-hydroxy-3:5-diiodobenzoate). A typical experiment showing table
11.
Both
heat, requiring
inhibition
systems
by
were
B.H.D.B.
is recorded in resistant to
unusually
2 hours at 100°C for
complete inactivation.
1. Gross, J., Pitt-Rivers, R. Lancet, 1952, i, 593. 2. Roche, J., Lissitzky, S., Michel, R. C.R. Acad.
Sci., Paris, 1952, 234, 1228. Maclagan, N. F., Wilkinson, J. H. Ann. Rep. chem. Soc. 1952, 49, 291. 4. Albright, E. C., Larson, F. C., Tust, R. H. Proc. Soc. exp. Biol., N.Y. 1954, 86, 137. 5. Wilkinson, J. H., Sprott, W. E., Bowden, C. H., Maclagan, N. F. 3.
Biochem. J. 1954, 56, 215. 6. Veall, N. Brit. J. Radiol. 1948, 21, 347.
369 The other
products
of the reaction
could not be
identified with certainty, but suggestive chromatographic evidence from the appearance (and subsequent destrucof
tion)
triiodothyronine
obtained in
was
experiments
with radioactive thyroxine and liver homogenates. OF 131I-LABELLED THYROXINE II—DEIODINATION BY RAT-LIVER HOMOGENATE, INHIBITION BY B.H.D.B. PHOSPHATE BUFFER AT pH 6.0, 38°C
TABLE
(4 µg.)
Radioactive iodide liberated
as
% substrate
radioactivity Time
(minutes) Thyroxine alone 8 50 68 82 80 87 85 82
0 15 30 60 90 120 150 180
Thyroxine + B.H.D.B. (5 x 10-4 M.) 8
33 35 37 40 40 43
This work was aided by grants from the Medical Research Council and from the governors’ discretionary fund of Westminster Hospital. We are indebted to Glaxo Laboratories Ltd., for supplies of L-thyroxine and L-triiodothyronine.
N. F. MACLAGAN M.D., D.Sc. Lond., F.R.C.P. Professor of Chemical Pathology in the University of London
W. E. SPROTT B.Sc., Ph.D. Lond. Research Assistant
DEFIBRILLATION OF THE VENTRICLES IN HYPOTHERMIA SINCE 1950, when the experimental work of Bigelow and his co-workers 8 introduced hypothermia as an adjunct to cardiac surgery, much further experimental work has been done and increasing numbers of clinical cases have been reported where the body-temperature has been reduced by 10°-15°C to permit surgery in the open heart.
Bigelow found, and subsequent reports confirm, that of the greatest dangers in hypothermia is ventricular fibrillation. This arrhythmia may arise spontaneously during cooling or rewarming, and particularly during one
interference with the heart ; and where the heart is already diseased or malformed the risk of this complicawhen ventricular fibrillacold heart the restoration of normal rhythm is especially difficult.g It may therefore be useful to describe a simple defibrillation technique, which in animals has proved rapidly and regularly successful and which probably does not damage the heart. In these experiments dogs were premedicated with and anaesthetised morphine gr. 1/4 and atropine gr. by intravenous injection of thiopentone sodium. Enough thiopentone was given initially to permit tracheal intubation and preparation of the femoral vessels for the arteriovenous cooling shunt by which hypothermia was
tion is greater. Unfortunately, comes on
in
a
7. Maclagan, N. F., Sprott, W. E., Wilkinson, J. H. Lancet, 1952, ii, 915. 8. Bigelow, W. G., Callaghan, J. C., Hopps, J. A. Ann. Surg. 1950,
132,
to
encountered)
ranging
from mild
surgical
insult
available for an open illtracardiac manoeuvre in a patient. The myocardium was now flaccid, and in such circumstances not only did cardiac massage fail to raise the blood-pressure adequately but electrical defibrillation proved unsuccessful. Occasionally, after long-continued massage, the tone of the myocardium improved ; the heart felt less flabby and a better blood-pressure was procurable. With such improvement electrical defibrillation was often possible, although fibrillation sometimes returned soon : I formed the impression that deflbrillation is difficult if not impossible unless myocardial tone is restored. To test this hypothesis I used adrenaline to increase myocardial tone and force of contraction. Injection of 1 ml. of 1’3000 adrenaline into the left ventricular cavity, followed by massage for a minute or two, caused a change in the " feel " Qf the myocardium as the drug perfused the coronary arteries. As soon as the heart became tight and hard under the massaging fingers, a single shock of 150 volts at 1 ampere and of duration about 1/5 second was administered, employing electrodes with a large contact area. Fibrillary activity disappeared from the surface of the ventricles and within a second or two a coordinated beat appeared. This procedure was carried out in twelve dogs and normal rhythm was restored in all cases with a single shock. This method appears to offer a reliable and rapid technique of defibrillation, occupying no more than 2 or 3 minutes. A single shock is unlikely to cause burning of the myocardium, which is not infrequently seen after the use of serial shocks. These observations on the previously normal hearts of hypothermic dogs do not necessarily apply to the diseased or malformed heart with which the surgeon may be dealing. In additional experiments, ventricular fibrillation was induced during hypothermia in three dogs in which cardiac dilatation had been produced at a previous operation by creating an interatrial septal defect and pulmonary stenosis. In these three dogs, after fibrillation had continued for 10 minutes, defibrillation was readily achieved by the technique described. It is noteworthy that in these abnormal hearts fibrillation was very easily
provoked.
SUMMARY
A simple technique is described for reversing the ventricular fibrillation often associated with hypothermia. Adrenaline is injected into the ventricular cavity and the heart is then massaged. When the tone of the myocardium has been restored, a single defibrillating electric shock is given, instead of the serial shocks commonly employed. This method was successful in all of twelve normal hypothermic dogs and also in three dogs with cardiac dilatation. E. G. BREWIN M.B. Leeds
531.
9. Swan, H., Zeavin, I., Holmes, J. H., Montgomery, V. 1953, 138, 360.
given during
prevent
’ Starling
difficulty
The results provide further evidence for the probable conversion of thyroxine to triiodothyronine in the body, and also support our theory of the mode of action of antithyroxine substances such as B.H.D.B.7 Since B.H.D.B. inhibits the metabolic efforts of thyroxine while augmenting those of triiodothyronine, its action appears to be completely explained by the inhibition of deiodination which we have demonstrated in vivo 5 and now also in vitro.
tion
were
gross shivering and to maintain light anæsthesia. The total quantity of thiopentone used was seldom more than J g., and cooling to a rectal temperature of 26°—27°C occupied 30-40 minutes. Artificial respiration was commenced soon after the start of cooling, using a Ideal ’ pump. Adequate but not excessive ventilation was provided ; however, an amount of ventilation which is adequate at normal temperature must constitute relativehyperventilation in hypothermia, because metabolism is much reduced. At a rectal temperature of 26’-27’C, thoracotomy was In a few cases, ventricular fibrillation performed. occurred spontaneously, and in the remainder it was induced by a variety of means (depending upon the
cooting
to a low-voltage shock. Such fibrillation was allowed to continue for about 10 minutes-roughly the time
47
Westminster Medical School
induced, and further small doses
Ibid,
Research Fellow in
Guy’s Hospital, London
Cardiovascular Surgery
Preliminary
a
pancreatic
Comment
Diagnosis in this case was confused only by the supposed rarity of large solitary stones arising from the pancreas. In fact the radiological evidence could fit but one condition-precisely that found at operation. Marshall (1938) points out that " the most important means of arriving at a diagnosis [of pancreatic stone] is a plain radiograph of the upper abdomen. Routine study of the gastro-intestinal tract with barium may hide the stones." In reviewing 36,000 consecutive necropsies Edmondson et al. (1950) found pancreatic calculi in 26 instances, in 6 of which they were solitary. Eliason and Welty (1948) collected 66 cases in which pancreatic stones were found at operation, and 6 were solitary. Lionello et al. in 1944 found 232 recorded cases of all types of pancreatic stone but others have since been reported from France (Cornet 1949, Bergeret 1952), Morocco, India, Brazil, and Finland. All these were multiple, and the only case of solitary stone I have found reported since 1946 was diagnosed by radiography and unconfirmed by operation or necropsy (Sarles et al. 1950). The largest solitary stone which I have seen mentioned was described by Shupman (quoted by Marshall 1938). Its size was 2-5 x 0-5 in. Most authors seem to agree that single stones arise from the pancreatic ducts and in their pathology resemble salivary calculi. No such agreement is found with regard to the multiple stones, which have been explained in various ways. In the management of my case it was a serious mistake, at the original operation, not to drain the region of interference in the pancreas. Evidently some pancreatic enzyme was released into both lesser and greater sacs when the tail of the pancreas was incised to remove the stone. This was, I think, the primary cause of the " burst abdomen," though the post-anaesthetic cough was an essential factor. Drainage would also have prevented the abscess in the lesser sac. I of
am
indebted to
Papua
the Director of Public Health, Territory and New Guinea, for permission to publish this case.
REFERENCES Bergeret, A. (1952) Arch. Mal. Appar. dig. 41, 9, 137. Cornet, A. (1949) Sem. Hôp. Paris, 25, 3054. Edmondson, H. A., Bullock, W. K., Mehl, J. W. (1950) Amer. J. Path. 26, 37. Eliason, E. L., Welty, R. F. (1948) Ann. Surg. 127, 150. Lionello, J., Ficarra, B. J., Ryan, N. H. (1944) Arch. Surg. 48, 137. Marshall, W. A. (1938) Radiology, 31, 562. Sarles, R., Sarles, H., Mathieu, H. (1950) Arch. Mal. Appar. dig.
39, 1170.
Communications
THE IN-VITRO DEIODINATION OF THYROXINE AND TRIIODOTHYRONINE DEIODINATION processes in the body have recently assumed importance in relation to thyroid function, as the result of the discovery of triiodothyronine 12 which appears to be the active form of the thyroid hormone. (This subject was reviewed by Maclagan and Wilkinson.3) While the deiodination of thyroxine has been amply demonstrated in intact animals, no unequivocal reports of in-vitro deiodination have appeared, although the probable conversion of thyroxine to triiodothyronine in rat-kidney slices has been announced by Albright, Larson, and Tust.4We have studied the production of iodide from thyroxine in homogenates from a number of rat tissues, employing both radioactive and non-radioactive thyroxine as substrate, and have been able to demonstrate active deiodination by both methods. After incubation the homogenates were precipitated with 5% trichloroacetic acid, and the iodide in the filtrate was estimated either by electrometric titration5 or by counting in the liquid Creiger-Muller counter of Veall.6 In the non-radioactive systems the level of substrate concentration used was 5 mg. of L-thyroxine per gramme of liver, and up to 20% the could be
of
thyroxine
TABLE I—DEIODINATION OF L-THYROXINE
(5 M&.)
HOMOGENATE AT DIFFERENT REACTIONS IN
Buffer
i
I I I
I
3.5
µg. per g.
liver
I
3-0
55
M./10
citrate
!
M/10
citrate
!
7-0
i! I
9-5
I
38°C
% total substrate iodine
!
2v 2.5 19.8 16-0 0-6 0-6
510 20 20
M/10 citrate
40 50 348 368 525 520 190 185
M/10 glycine M/10 glycine
10-5
I
65 5 80 630
M/10 citrate
9-0
HOURS AT
Iodide liberated
,
PH n
BY RAT-LIVER
18
M/10 glycine
I
1-3 1-6 10.9 116 16-5 163 6-0
,
5-8 _ _
deiodinated in 18 hours at pH 35 or at pH 9.5. A typical is shown in table I. This liver system also attacked L-triiodothyronine under the same conditions, giving 7% deiodination at pH 9.5 but being without effect at pH 3-5. It was inhibited by exclusion of air and by cyanide but not by citrate nor by anti-thyroxine substances. In the radioactive systems (4 !1-g. of 131I-L-thyroxine per g. of tissue) up to 80% of deiodination was recorded in 3 hours at pH 6-0 as shown in table 11. This reaction was most prominent in liver homogenates but could also be demonstrated in homogenates from brain, kidney, muscle, spleen, adrenal, thyroid, and intestinal mucosa. In the case of liver it was inhibited not only by exclusion of air and by cyanide but also by citrate and by two typical anti-thyroxine substances (n-butyl 4-hydroxy-3: 5-diiodobenzoate (B.H.D.B.) and
experiment
&bgr;-hydroxyethyl 4-hydroxy-3:5-diiodobenzoate). A typical experiment showing table
11.
Both
heat, requiring
inhibition
systems
by
were
B.H.D.B.
is recorded in resistant to
unusually
2 hours at 100°C for
complete inactivation.
1. Gross, J., Pitt-Rivers, R. Lancet, 1952, i, 593. 2. Roche, J., Lissitzky, S., Michel, R. C.R. Acad.
Sci., Paris, 1952, 234, 1228. Maclagan, N. F., Wilkinson, J. H. Ann. Rep. chem. Soc. 1952, 49, 291. 4. Albright, E. C., Larson, F. C., Tust, R. H. Proc. Soc. exp. Biol., N.Y. 1954, 86, 137. 5. Wilkinson, J. H., Sprott, W. E., Bowden, C. H., Maclagan, N. F. 3.
Biochem. J. 1954, 56, 215. 6. Veall, N. Brit. J. Radiol. 1948, 21, 347.
369 The other
products
of the reaction
could not be
identified with certainty, but suggestive chromatographic evidence from the appearance (and subsequent destrucof
tion)
triiodothyronine
obtained in
was
experiments
with radioactive thyroxine and liver homogenates. OF 131I-LABELLED THYROXINE II—DEIODINATION BY RAT-LIVER HOMOGENATE, INHIBITION BY B.H.D.B. PHOSPHATE BUFFER AT pH 6.0, 38°C
TABLE
(4 µg.)
Radioactive iodide liberated
as
% substrate
radioactivity Time
(minutes) Thyroxine alone 8 50 68 82 80 87 85 82
0 15 30 60 90 120 150 180
Thyroxine + B.H.D.B. (5 x 10-4 M.) 8
33 35 37 40 40 43
This work was aided by grants from the Medical Research Council and from the governors’ discretionary fund of Westminster Hospital. We are indebted to Glaxo Laboratories Ltd., for supplies of L-thyroxine and L-triiodothyronine.
N. F. MACLAGAN M.D., D.Sc. Lond., F.R.C.P. Professor of Chemical Pathology in the University of London
W. E. SPROTT B.Sc., Ph.D. Lond. Research Assistant
DEFIBRILLATION OF THE VENTRICLES IN HYPOTHERMIA SINCE 1950, when the experimental work of Bigelow and his co-workers 8 introduced hypothermia as an adjunct to cardiac surgery, much further experimental work has been done and increasing numbers of clinical cases have been reported where the body-temperature has been reduced by 10°-15°C to permit surgery in the open heart.
Bigelow found, and subsequent reports confirm, that of the greatest dangers in hypothermia is ventricular fibrillation. This arrhythmia may arise spontaneously during cooling or rewarming, and particularly during one
interference with the heart ; and where the heart is already diseased or malformed the risk of this complicawhen ventricular fibrillacold heart the restoration of normal rhythm is especially difficult.g It may therefore be useful to describe a simple defibrillation technique, which in animals has proved rapidly and regularly successful and which probably does not damage the heart. In these experiments dogs were premedicated with and anaesthetised morphine gr. 1/4 and atropine gr. by intravenous injection of thiopentone sodium. Enough thiopentone was given initially to permit tracheal intubation and preparation of the femoral vessels for the arteriovenous cooling shunt by which hypothermia was
tion is greater. Unfortunately, comes on
in
a
7. Maclagan, N. F., Sprott, W. E., Wilkinson, J. H. Lancet, 1952, ii, 915. 8. Bigelow, W. G., Callaghan, J. C., Hopps, J. A. Ann. Surg. 1950,
132,
to
encountered)
ranging
from mild
surgical
insult
available for an open illtracardiac manoeuvre in a patient. The myocardium was now flaccid, and in such circumstances not only did cardiac massage fail to raise the blood-pressure adequately but electrical defibrillation proved unsuccessful. Occasionally, after long-continued massage, the tone of the myocardium improved ; the heart felt less flabby and a better blood-pressure was procurable. With such improvement electrical defibrillation was often possible, although fibrillation sometimes returned soon : I formed the impression that deflbrillation is difficult if not impossible unless myocardial tone is restored. To test this hypothesis I used adrenaline to increase myocardial tone and force of contraction. Injection of 1 ml. of 1’3000 adrenaline into the left ventricular cavity, followed by massage for a minute or two, caused a change in the " feel " Qf the myocardium as the drug perfused the coronary arteries. As soon as the heart became tight and hard under the massaging fingers, a single shock of 150 volts at 1 ampere and of duration about 1/5 second was administered, employing electrodes with a large contact area. Fibrillary activity disappeared from the surface of the ventricles and within a second or two a coordinated beat appeared. This procedure was carried out in twelve dogs and normal rhythm was restored in all cases with a single shock. This method appears to offer a reliable and rapid technique of defibrillation, occupying no more than 2 or 3 minutes. A single shock is unlikely to cause burning of the myocardium, which is not infrequently seen after the use of serial shocks. These observations on the previously normal hearts of hypothermic dogs do not necessarily apply to the diseased or malformed heart with which the surgeon may be dealing. In additional experiments, ventricular fibrillation was induced during hypothermia in three dogs in which cardiac dilatation had been produced at a previous operation by creating an interatrial septal defect and pulmonary stenosis. In these three dogs, after fibrillation had continued for 10 minutes, defibrillation was readily achieved by the technique described. It is noteworthy that in these abnormal hearts fibrillation was very easily
provoked.
SUMMARY
A simple technique is described for reversing the ventricular fibrillation often associated with hypothermia. Adrenaline is injected into the ventricular cavity and the heart is then massaged. When the tone of the myocardium has been restored, a single defibrillating electric shock is given, instead of the serial shocks commonly employed. This method was successful in all of twelve normal hypothermic dogs and also in three dogs with cardiac dilatation. E. G. BREWIN M.B. Leeds
531.
9. Swan, H., Zeavin, I., Holmes, J. H., Montgomery, V. 1953, 138, 360.
given during
prevent
’ Starling
difficulty
The results provide further evidence for the probable conversion of thyroxine to triiodothyronine in the body, and also support our theory of the mode of action of antithyroxine substances such as B.H.D.B.7 Since B.H.D.B. inhibits the metabolic efforts of thyroxine while augmenting those of triiodothyronine, its action appears to be completely explained by the inhibition of deiodination which we have demonstrated in vivo 5 and now also in vitro.
tion
were
gross shivering and to maintain light anæsthesia. The total quantity of thiopentone used was seldom more than J g., and cooling to a rectal temperature of 26°—27°C occupied 30-40 minutes. Artificial respiration was commenced soon after the start of cooling, using a Ideal ’ pump. Adequate but not excessive ventilation was provided ; however, an amount of ventilation which is adequate at normal temperature must constitute relativehyperventilation in hypothermia, because metabolism is much reduced. At a rectal temperature of 26’-27’C, thoracotomy was In a few cases, ventricular fibrillation performed. occurred spontaneously, and in the remainder it was induced by a variety of means (depending upon the
cooting
to a low-voltage shock. Such fibrillation was allowed to continue for about 10 minutes-roughly the time
47
Westminster Medical School
induced, and further small doses
Ibid,
Research Fellow in
Guy’s Hospital, London
Cardiovascular Surgery