Physrev 1921 1 2 295 PDF
Physrev 1921 1 2 295 PDF
Physrev 1921 1 2 295 PDF
HENRY G. BARBOUR
From the Departmbt of Pharmacology, Yale University School of Medicine
while the muscles show a much greater rise; or with more extreme
degrees of refrigeration the muscle curves show less fall in temperature
th an the other curves. This h.e associates with the augmented activity
of the muscles in regulating against co1.d. Lefevre (91) maintains,
however, that liver and muscle temperatures run parallel during refrig-
eration, and ascribes to the liver 30 per cent and to the muscles 40
per cent of thermogenesis; but Magne attributes to the muscles 70 to
80 per cent.
The ‘I surface temperature” of the body is much less uniform than
is generally supposed. ‘Benedict,, Miles and Johnson (18) find that the
temperature of the skin even with well-clothed individuals exhibits
differences of 4” to 5OC. in various localities.
As an insulator the efficiency of the human skin varies according to
the predominance of fat, corium, or epidermis (157). The epidermis
has the poorest heat conductivity, heat passing through fat and through
corium respectively two and three times as readily. Variations in the
fluid content of its capillaries naturally alters the conductivity of the
living skin.
The heat conductivity of the cranium appears to be relatively good.
Leyton and Sherrington (94) found that in a chimpanzee with a cranial
vault about the thickness of the average human, the application of
local cold (ice bag) or heat over the parietal scalp rapidly affected the
temperature of a thermometer bulb lying under the dura against the
cerebral surface, directly beneath the region of thermal application.
Average body temperature. Precise determination of the average
temperature of the body appears at present impossible. Barr and
DuBois (16) have, however, devised a differential method by which
changes in average body temperature may be determined in a calori-
meter. For a given interval they determine the difference between the
number of calories produced and the number eliminated. This* dif-
ference, when divided by the thermal equivalent, affords the gain or
loss in average body temperature. For example, heat production,
100 calories, minus heat elimination, 60 calories = heat stored, 40
calories. In a 70 kilo man, the thermal equivalent = 58.1. The
40
average temperature gain is therefore - = 0.66’.
58.1
REGULATION AGAINST COOLING : ChemicaZ regulation. In animals
with well-developed physical regulation chemical regulation only
appears as the external temperature descends below 14-15OC. But
many instances may be cited (99) in which external temperatures of
The studies of Lusk upon the influence of cold baths show that
heat production may increase by as much as 81 per cent of the normal.
(Schapals (137) has described an increase of 176 per cent in the oxygen
consumption.) The material first burned is sugar, for the respiratory
quotient gradually sinks. In the case of the chemical regulation of the
waking hedgehog, however, Henriques (61), contrary to other authors,
finds the extra heat produced apparently at the expense of fat and not
of carbohydrate; the respiratory quotient remains at about 7.
According to Mansfeld and Pap (107 a) the blood of cooled rabbits
can augment the sugar consumption of the heart.
Physical regulation. Down to environmental temperatures of about
15°C. apparently the so-called physical regulation suffices to maintain
a fairly constant body temperature. The stimulus is from without
(38). By means of this physical regulation the blood, as the most
superficial observation shows, is driven away from the surface of the
body. e It has been customary to assume that this was due simply to a
redistribution of the blood, for example, the internal organs increase
rapidly in volume as well as in temperature under these conditions.
(The various effects of cold baths are reviewed by Matthes (110) .)
It has been noted, however, that hemoglobin, red-blood cell count and
viscosity increase under the influence of a cold environment. Decrease
in blood coagulation time has also been described by Velden (152).
Under our present conceptions such acute changes must be attributed
to alterations in the fluid concentration of the blood.
The effects of cold baths on (‘brain volume” as determined by the
cranial plethysmograph are to cause an increase. How much of this is
due to an increase of the cranial blood supply (120), (148)) how much
to increase in the cerebra-spinal fluid, or how much to actual taking
up of water by the nerve tissue has not been determined.
These cranial volume effects are evidently associated primarily with
increases in blood pressure as shown for example by L. Hill (69), but I
have found in dogs that the cranial volume may continue to increase
during the return of blood pressure to normal. Since this increase in
brain volume is associated with a loss of fluid from the blood the possi-
bility exists of gradual imbibition by the nervous tissue.
REGULATION AGAINST OVERHEATING: The danger of overheating, as
pointed out by L. Fredericq (38), usually arises from within the body
rather than from the environment, which affords the excessive cold
stimuli. In this connection it is interesting to note that Ruffini’s cor-
puscles, the temperature sense nerve endings for heat, are situated in
the deeper layers of the skin, as pointed out by Ebbecke (32), in con-
tradistinction to the cold sense nerve endings (Krause’s bulbs) which
lie at the junction of the epidermis and the cutis Vera.
It is probable, however, that application of heat either to the skin or
to the base of the brain yields similar results (see below).
Filehne (35) has apparently shown that for the initiation of the proc-
esses which regulate against overheating no rise in blood temperature
is necessary. For in a bath up to the neck at 41 to 42OC. , sweating of
the forehead began prior to any change in rectal temperature; plunging
a hand into cold water stopped this sweating at once.
Chemical regulation. Cessation of the chemical heat regulation is
seen in the transition from shivering temperatures to higher ones.
When the external temperature is raised from 26 to 37OC. heat produc-
tion in rats, as shown by A. M. Hill, (67), is reduced by but one-quarter
of the amount which it is reduced when the temperature is raised from
15 to 26’. It is difficult to prove that tlhe heat production is reduced
as a measure against overheating in an individual who is quite inactive
before the heat stimulus is applied. Barbour and Prince (13) SUC-
ceeded in reducing the COz output of rabbits by heating the basal
nuclei and offered evidence indicating that diminished metabolism is
one of the factors reponsible for the temperature fall. At high tem-
peratures Lapicque (89) showed that the metabolism of birds is re-
ducible only to a certain minimum. Hot baths, according to Schapals
(137), appear to increase heat production by 22.5 per cent. The in-
creased heat production in these instances is of course attributable to
the rise in body temperature and has nothing to do with the chemical
regulation,
According to Mansfeld and Pap (107 a) the blood of heated rabbits
can reduce sugar consumption by the heart.
Physical regulation. This defense against overheating involves
evaporation of water from the lungs and skin as well as direct radiation
and conduction of heat from the surface of the body.
Both evaporation and radiation are favored by an increased blood
flow through the skin. According to the older views vasomotor shifts of
blood to the surface at the expense of the interior were chiefly respon-
sible for the increased surface blood flow, but it now appears that the
value of these shifts may be much enhanced by augmented blood
volume, brought about by rapid dilution (6). The water thus made
available serves in the evaporation and radiation processes.
Cold . . . . . . . . . . . . . . . . . . . . . . . . . . . . + + -
Heat. . . . . . . . . . . . . . . . . . . . . . . . . . . . . - - +
tions under which the exercise is carried out are such that sweating
does not occur. Furthermore sweating procedures such as electric-
light heat baths in the entire absence of muscular activity do produce
this flow of protein-salt-solution from the tissues into the blood.
The conclusion is that this dilution of the blood is a response to stim-
ulation by heat Whether the sweating mechanism is the one that is
primarily set into action through the temperature-sense nerve endings
and the central nervous system, and the water thus lost from the blood
replaced by a fluid-regulating mechanism of some sort which over-
compensates, or whether the heat directly affects this fluid-regulating
mechanism without first drawing off water through the sweat glands
has not been determined.
The temporary decrease in white blood cells under the influence of
dry heat described by Murphy and Sturm (122) may be another expres-
sion of blood dilution.
Under some conditions fluid may be drawn into the blood and then
lost by excretion without any dilution of the blood being detected.
This is indicated in the experiments of Young, Breinl, Harris and
Osborn (161), who found under t)ropical conditions of heating asso-
ciated with a considerable rise of body temperature, that the blood
(as determined by hemoglobin tests) became somewhat concentrated.
Conditions of overheating, brought about by raising the temperature
of the environment, result in a 50 per cent diminution of the flow of
gastric secretion excited by sham feeding with Liebig’s meat extract
(36). It does not appear in these experiments whether the blood was
concentrated or diluted at the time of inhibited gastric secretion.
As regards regulation by evaporation of water from the surfaces of
the body Soderstrom and DuBois (144) found that in normal men,
age 20 to 50, the average secretion of water through the skin and air
passages is 29 grams per hour; 24 per cent of the heat produced is thus
lost. In boys and old men the amount is a little more.
Osborne (127) has shown that the expired air is probably satura,ted
with moisture under all conditions. The heat output by the lungs
can only vary with changes in their ventilation; heat polypnea will be
referred to later on.
Galeotti and Macri (44) have shown that the insensible perspiration
averages 0.12 gram per square decimeter per hour on the anterior
region of the forearm of normal persons at 23°C. While it is claimed
that this may become totally inhibited when the temperature of the
environment is considerably reduced, it of course becomes increased
by heating.
Freund (39) ascribes this marked difference between the effect of the
lower cervical and the upper thoracic operation to the severance of
sympathetic paths leading to the abdominal viscera. More recently
he has shown that by performing in addition to the dorsal cord opera-
tion a double vagotomy just below the diaphragm, animals become
poikilothermic to essentially the same extent as those with cervical
cord section. This is probably dues to the severance of sympathetic
fibers. If instead, the dorsal cord operation be supplemented either
by removal of the stellate ganglion or bv section of the eighth cervical
and first dorsal roots a similar loss of heat regulation will ensue.
Freund and Grafe (40) have made extensive studies of the metab-
olism of animals with various cord operations. Dorsal cord section
plus double vagotomy was found to increase the total metabolism, and
especially the protein loss. In explanation the removal of central
inhibitions is suggested. After such an operation infectious agents,
including trypanosomes, swine-pest bacilli, or hay infusion, increase
neither metabolism nor body temperature. This argues against a
toxogenic protein decomposition in infectious fevers.
Hari and Janney (56), however, have failed to find that cord opera-
tions increase the total metabolism. They state that metabolism
becomes diminished by one-quarter or more by cervical section, while
below this no effect is produced except possibly a slight increase.
Hannemann (55) states that in frogs the gaseous exchange is increased
by decerebration.
Investigations on the brain. Since Ott’s (128) time many have
attempted a more accurate localization of anatomical “heat centers.”
(See Liljestrand and Frumerie (95), also Jacobj and Roemer (75).)
The results in general have been inconclusive, although the best results
from “heat puncture” have usually resulted when the basal nuclei
were involved. The last-mentioned authors regard irritation, disten-
tion or hyperemia of the walls of the lateral ventricle as the essential
cause of heat puncture hyperthermia. They find that corrosives such
as phenol or mercury when introduced into one of the lateral ventricles
also produce hyperthermia.
The subthalamic region was successfully punctured by Barbour and
Wing (15) in experiments where the needle was passed through the
orbital fossa instead of from above and the relation of this to Isen-
schmid and Krehl’s (74) and Citron and Leschke’s (26) operations
appears to make this point of considerable significance. These facts
suggest coordination between heat regulation and the pituitary
ilar to that seen with cold baths. During this concentration Barbour
and Freedman (9) observed a marked reduction in the salivary response
to pilocarpine. This accords with the reduced gastric secretion in
fever noted by Meyer, Cohen and Carlson (114).
hTervous. regulation in fever. In fever it is said that the body ther-
mostat is “set at a higher level.” A normal temperature becomes
apparently interpreted as “cold” by the temperature centers, while
one of 40’ perhaps feels “neutral.” Similarly the skin nerves seem
hypersensitive to cold, or hyposensitive to heat, whence the subjective
“ chill.”
This alteration in sensitivity on the part of the nervous apparatus
might be attributed to a depressing action of toxins upon the nervous
system. In accord with this idea Head and Riddoch (59) note in all
febrile conditions a diminished responsiveness of the severed spinal
cord. Storm Van Leeuwen (147) finds that 38OC. is the optimum
condition for the transmission of reflexes through the cord. They dis-
appear entirely at 42”. Furthermore because of the production of
polypnea by a central action Nikolaides and Dontas (125) state that
the effect of antipyretics on the heat center is one of stimulation.
Because of the effects of “ stimulating” the base of the brain mechan-
ically, electrically, etc., it has been said that the heat centers are “stim-
ulated” in fever. If one explains fever by the dual heat center theory
of Hans Meyer (113) one may say that the ” cooling center” is depressed
while the “heating center” is stimulated. Grafe (51) has attributed
fever to the supposed irritating action of the decomposition products of
bacteria or of the injuredtissues upon the heat centers. By the intra-
cerebral introduction in properly sensitized animals of Xb to ia the
necessary intravenous dose of serum, Hashimoto (58) has produced
anaphylactic fever.
That the nervous mechanism is essential to some fevers is shown by
the failure of infectious agents to act after mid-brain section (26), (76)
and after cord section (40), (142).
Water and salt balance in fever. It has been pertinently objected, how-
ever, that some fevers can be produced in the absence of the heat-
regulating mechanism, notably the sugar dehydration hyperthermia of
Woodyatt (5). This investigator rejects the neurogenic theory of
fever and advances the idea that the central fact to which a positive
heat balance must be attributed is a deficit of free water in the body.
Water regulation he admits, however, may in part be under vasomotor
nervous control.
the blood. Since they as a rule increase the blood sugar this fact
may be brought into relation with their antipyretic action, as will
appear below.
Antipyretics. Substances which reduce the temperature in febrile
and similar states but not in normal conditions unless the dosage be
excessive are termed antipyretics.
Acetyl-salicylic acid in doses reducing fever temperature by l°C.
increased heat elimination in my series of cases by 38 per cent. Simi-
larly, a decrease in elimination was observed during the return to fever
temperature. The heat production was but little altered. Antipy-
reties therefore act chiefly upon the heat-dissipating mechanism.
Barbour and Herrmann (IO) have contributed evidence bearing on the
mechanism of the increase in heat elimination. Salicylates, antipyrine
and quinine, in dogs under normal conditions, tend to increase slightly
the body temperature and blood solids. In coli fever these drugs
dilute the blood, thus accounting for the fall in temperature. All
these substances increase the blood sugar which (by osmosis) may
account for the blood dilution in febrile cases, in which the water
reserve of the tissues is increased at the expense of the blood.
Antipyretics inhibit adrenalin glycosuria, but Mansfeld and Purjesz
(108) have shown that this is a renal effect; thus an antidiuretic effect
favoring increased blood sugar and blood volume is obtained.
Dextrose, intravenously given, as shown by Barbour and Howard
(12), resembles the antipyretics in that it reduces the temperature in
fever, causing the blood to become more dilute than under normal
conditions. This supports the contention that blood sugar plays a
role in antipyretic action. Barbour and Baretz (7) found that acacia
similarly tends to dilute the blood in fever and to reduce the tempera-
ture, which it does not do in normal animals.
Wiechowski (155) showed that antipyrine and similar substances
relax the brain vessels in fever but not in normal animals.
Notwithstanding the central action of antipyretic drugs Yamamoto
(159) noted no appreciable difference in the amounts of salicylic acid
and acetyl-salicylic acid present in brain tissue in rabbits, although the
latter drug is much more powerful than the former.
According to Piccini (129) antipyrine, phenacetine and acetanilid
all diminish the total oxygen of the arterial blood.
Hashimoto (58) noted certain differences between antipyrine and
salicylates on the one hand and quinine on the other. The antipyretic
effect of the former could be increased by the heat stimulus to the
39 /
I
I
38 20
37 18
36 16
3ti 14
10
Fig. 1. Effects of cool (20°C.) bath upon dog with and without nervous heat
regulation. Upper two curves, normal dog; lower two curves, dog after section
of sixth cervical cord segment; continuous lines, temperature; broken lines, blood
solids.
Note that normal dog keeps temperature from falling by means of blood con-
centration. Cord section dog is poikilothermic because blood concentrating
mechanism is broken down.
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