ON THE DIRECT INFLUENCE 
OF 
MEDICINAL AND MORBIFIC 
AG E N T S 
UPON’ THE 
MUSCULAR TISSUE OF THE BLOOD-VESSELS. 
BY 
R. CRESSON STILES, M. D, 
PHYSICIAN TO KINGS COUNTY HOSPITAL. 
“Non fingendum, aut excogitandum, sed inveniendum.” 
READ BEFORE THE KINGS COUNTY MEDICAL SOCIETY, 
Brooklyn, March 21st, 1865. 
NEW YORK: 
PRINTED BY C. A. ALVORD, 
15 VANDEWATER STREET. 
1865. ON THE 
ACTION OF MEDICINES ON THE BLOOD-VESSELS. 
The following experimental researches were undertaken with the de- 
sire of extending, as far as possible, the influence of the anatomical gener- 
alizations of Bichat and the discoveries of modern histologists into the 
domain of practical medicine. The field of research was chosen as near 
as possible to that of practical medicine, in order that the results of exper- 
iment might be controlled by the experience of numerous observers 
among practitioners, instead of affording interest to the professed culti- 
vators of abstract physiology merely, whose numbers are few, and with 
the tendency of whose pursuits whatever there is of magisterial influence 
and of practical conservatism in medical authority has but limited sym- 
pathy. Physiology is not far in advance of the position which chemistry 
held before the time of Lavoisier, but the movement which is drawing 
within the domain of the Science of Vital Dynamics the dependent science 
of Pathology (dependent, if legitimate scientific dependence exist at all), 
which leads the physician to seek in diseases the affections of an organism 
reacting in accordance with definite laws, rather than entities whose 
slightest variations in form and shade, in flying clouds of symptoms, are to 
be depicted in endless and useless detail, must affect also the classification 
and employment of therapeutic agents. 
The several tissues of the body manifest varied and delicate differences 
of reaction to the agents employed in their study. These differences, due 
to molecular constitution, they doubtless possessed, with others of still 
greater delicacy, while forming a part of the living organism, rendering 
them subject to the variations of nutrition or function, which are the 
essential elements in all medicinal action. The influence of sulpho-cyanide 
of potassium* and of upas upon the voluntary muscles, that of strychnine 
upon the afferent nerves, and that of wourara upon the motor nerves, 
give proof of relations subsisting between these substances and tissues 4 
respectively which other tissues do not share, or in which they participate 
to hut a slight extent. The power of carbonic oxide gas to paralyze the 
blood corpuscles, rendering them inert in hsematosis, and that of a temper- 
ature of 115° Fahrenheit to paralyze and make rigid the voluntary muscles, 
while the same temperature leaves the motor nerves intact, lend further 
proof of the independent vital reactions of the different anatomical elements 
of the body. That these relations should be more familiar to physiologists 
than to practitioners is simply because they have been studied by the for- 
mer; that many of the most familiar and most useful articles of the 
materia medica have like relations I propose to show. Similar considera- 
tions are applicable to the generation of diseases. The development of the 
Trichina Spiralis in the striated muscles exclusively, its presence ceasing, as 
T have seen it, with the upper third of the oesophagus, leaving the remain- 
der of an apparently homogeneous canal uninfested, is a type of the mode 
in which other less vitalized morbific agents seek out certain tissues of 
particular physical or molecular constitution upon which to exert their 
activity. 
Some of the most valuable revelations of experimental physiology have 
resulted from the study of the nervous system. The demonstration of the 
separate motor and sensory endowments of the anterior and posterior 
spinal nerves by Bell and Magendie, the determination of the powers of the 
principal centers of the cerebro-spinal system by Marshall Hall, Flourens 
and Longet, the recognition of the influence of the sympathetic upon 
nutrition, calorification, secretion, and the activity of the nervous centers 
by Bernard and Brown-Sequard, are examples of what has been accom- 
plished in this field of research. It is characteristic of the nervous system, 
that its functional activity is brought into play by the simplest physical 
influences, rendering it particularly suited to experimental investigation. 
To the student of experimental physiology, or to the pathological anato- 
mist, the fact cannot fail to present itself, that the office of the nervous 
system is rather of a passive nature, serving to call into action and regulate 
processes of far greater independence; both are led to regard the nervous 
system as an instrument whose wonderful harmonies are evoked by the 
play of forces external to itself. Not only has experiment shown that in 
death from inanition, while the blood loses over seven-tenths of its weight, 
and the muscles over four-tenths, the loss of the nervous system is less 
than one-fiftieth; but when we witness on post-mortem examinations the 
almost uniform complete integrity of the nervous system amid the wreck 
of other systems and the waste and decay of the rest of the body, and after 
death accompanied with the most violent nervous commotions, we are 5 
forced to regard the nervous system as an instrument of sluggish nutritive 
changes, rather acted upon by the blood and the organs which it supplies, 
than itself generating its own forces and possessing the active nutrition 
necessary to such manifestations of energy. The nervous system has too 
long given sanctuary to all manner of fugitives from physiological law. 
Except from our own individual sensations, we know nothing of nervous 
action but by muscular action, and it becomes exceedingly important 
therefore to determine whether the nervous system is not merely one of 
the instruments through which muscular activity is aroused, or whether 
physical and chemical agents do not exercise a direct and immediate influ- 
ence upon muscular tissue through the medium of the blood. 
Both Harvey and Haller denied the irritability or muscular contractility 
of the arteries. The contractile phenomena presented by the blood-vessels 
were believed by Bichat to be due to tonicity, an endowment different 
altogether from muscular contractility. “ Respecting the final arterial 
ramifications,” says Magendie, in 1822, “as the vessels which constitute 
them are so small as to be invisible, at least in a state of health, no one 
can either affirm or deny that they are irritable. It would follow from 
analogy, however, that they have no sensible movement. In cold-blooded 
animals, it is easy to see the blood circulating in these vessels, and even 
passing into the veins, but these same vessels give no sign of contraction.” 
These views, thus attested, may be considered as those of the profession 
generally, till completely reversed by the revelations of the microscope. 
Since the discovery of the elements of the non-striated muscular tissue or 
fiber-cells by Kolliker, in 1847, and their recognition in the arteries and 
arterioles, the question has been set completely at rest. Numerous exper- 
imenters have studied the influence of mechanical irritation, of galvanism, 
of heat and cold, and of various medicinal substances upon the caliber of 
the vessels, and the rapidity of the circulation in the transparent tissues of 
the lower animals. The most real and decided of the recent triumphs of 
experimental physiology have been the result of researches upon the 
influence of the nervous system upon the circulation, as regulated by the 
muscular tissue of the blood-vessels, placing under the control of the 
experimenter the functional activity of various organs, and enabling him 
to produce at will the fundamental pathological phenomena of inflamma- 
tion, hypertrophy, atrophy, and degeneration. But it is impossible to 
resolve these results into their elements. The solution of the simplest 
physiological problem is rendered difficult by the complexity of the con- 
ditions under which it is presented. Our present problem is to determine 
the influence of certain agents upon the living muscular tissue of the 6 
blood-vessels, so as to be able to assign to this influence the part it plays 
in the involved phenomena of the action of these agents when used as 
remedies, or otherwise acting upon the human system; or, given a medi- 
cinal article, to determine whether, when brought into contact with the 
muscular tissue of a living artery, it produces its contraction, relaxation, 
paralysis, or a succession of these states; in what proportions used, and 
under what conditions these effects may be looked for with certainty. A 
step only towards its solution is still a step in advance. 
The earliest and simplest observations made in this direction were on 
the obvious effects of cold and haemostatic applications. By such obser- 
vations, and by experiment, Hunter distinguished the elasticity of the 
arteries from their contractility, and recognized the persistence of the 
endowment of irritability long after death. He divided longitudinally 
arteries of different caliber, and determined, by measurement, the part in 
their contraction due to elasticity, and that due to physiological contrac- 
tility, recognizing, before the microscope had shown that the smallest 
arteries are entirely wanting in elastic tissue, while, their muscular tunic 
is well developed, that contractility has the largest influence upon the 
smallest arteries. He showed that contractility had no influence on the 
length of the arteries before minute anatomy had demonstrated the circu- 
lar arrangement of their contractile elements. Kblliker experimented on 
the arteries of an amputated limb with a galvanic current, and produced 
contractions and constrictions of the popliteal and posterior tibial for an 
hour after the operation. 
I have already alluded to experiments on the circulation in the trans- 
parent tissues of the lower animals, as seen by the microscope. These are 
now of vulgar performance, but it was not so when Schwann announced 
that he had produced successive contractions to one-third of their diam- 
eter in the mesenteric arteries of the toad by successive applications of 
cold water; or Ed. Weber reported having reduced the mesenteric arteries 
of the frog to one-sixth of their original diameter by an interrupted galvanic 
current. Numerous medicinal substances have since been tested in this 
manner, but the direct effect of the agents employed upon the muscular 
tissue is here involved with that upon the nerves, either directly or 
through reflex action, with the results of endosmose and exosmose, and 
with numerous other complications; and both the classes of experiments 
I have mentioned lack the quantitative determination, which is the surest 
basis of scientific generalization. Resort must be had to simpler methods. 
The quantities of a liquid discharged through inert tubes of a caliber, 
such that the effects of friction are inconsiderable, are, other conditions 7 
remaining the same, as the squares of the diameters of the tubes. As the 
tubes diminish in size, the effects of friction become more important, till, 
in capillary tubes, according to Poiseyille, the quantities discharged are 
inversely as the length of the tubes, and directly as the fourth power of 
their diameters. It follows, therefore, that a cause which would reduce 
the diameter of a capillary tube one-half, would reduce the amount of 
liquid discharged to one-sixteenth. Obviously the most accurate method 
of estimating the effect of delicate influences upon the caliber of the 
blood-vessels is that of measuring the amount of liquid they permit to 
pass through them under given conditions. 
Poiseuille observed, also, that minute differences in the constitution 
of the liquids exerted a decided influence upon the rapidity of their flow 
through capillary tubes. Thus, the flow of serum was retarded by alcohol 
in such quantities as might be supposed often mingled with the blood 
during life, and that of the alcoholic serum accelerated by ammonia, and 
he argues that the beneficial effects of ammonia in drunkenness are due 
to this antagonistic influence. On injecting acetate of ammonia into the 
blood of a horse, he reduced the time of the round of the circulation 
from twenty-five and thirty seconds to eighteen and twenty-four seconds, 
and increased it to thirty-five and forty seconds with chloride of sodium. 
Iodide of potassium, nitrate of potassa, and chloride of ammonium, in- 
creased the rapidity of the circulation in animals, and of the liquid flow 
in inert tubes. Although his deductions from these experiments are mani- 
festly unwarrantable, the influences which they reveal are important, 
and should not be neglected; they should not be allowed to vitiate the 
result of experiments on muscular irritability. 
After numerous trials of apparatus and liquids in the endeavor to 
avoid sources of error, the following arrangement was adopted for a 
course of systematic experimentation. A reservoir is placed four feet 
above the operating table, to the bottom of which is adapted a long tube 
of caoutchouc terminated by the nozzle of a syringe for anatomical injec- 
tion. The tube is coiled in another reservoir on the table, of a capacity 
of several gallons, into which water at any required temperature may be 
introduced, and lose heat slowly. The temperature of the liquid in this 
reservoir is that of the liquid discharged from the mouth of the tube, 
when the upper reservoir has been filled and the current allowed to flow. 
It is not raised above 110° Fahrenheit, nor allowed to fall below 100°. 
The liquid most used was a solution of sugar, of a specific gravity of from 
1025 to 1030, perfectly neutral, not abstracting water from muscular 
fibers nor imbibing them, but permitting them to maintain their irritability 8 
for a long period when immersed in it; not affecting the artery experi- 
mented on in its passage through it otherwise than mechanically. Blood 
and serum from the lower animals were employed occasionally to control 
the results obtained with the saccharine solution. The arteries experi- 
mented on were chiefly those of the umbilical cord, which the lying-in 
ward of a large hospital furnishes in abundance, and which are peculiarly 
adapted for the purpose. Other arteries were employed, and even whole 
organs of the lower animals, recently killed, were connected by their arteries 
with the apparatus, for the purpose of studying the capillary circulation. 
The lower reservoir serves also as a water-bath, in which vessels con- 
taining the medicated solutions are immersed, their temperature being 
also that of the liquid flowing through the artery. The artery having 
been adapted to the tube, and the rate of flow through it measured, the 
current is arrested, the artery is suspended for a given time in the medi- 
cated solution, and the rate of flow is again measured. Or, the rate of 
flow having been measured, the substance to be tested is mingled in given 
proportion with the liquid in the upper reservoir, and thus allowed to act 
on the interior of the artery as in the circulation of the blood. 
The arteries of the umbilical cord contain no elastic tissue, blood-ves- 
sels, nor nerves, but their muscular tunic is remarkably developed, 
imbedded merely in a loose connective tissue. No other large blood- 
vessel presents so completely the simple, uncomplicated phenomena of 
muscular contractility. Virchow, in his Cellular Pathology, has given a 
true description of the umbilical cord, showing the organized structure 
of the so-called gelatine of Wharton, and its likeness to the vitreous humor 
of the eye. He mentions the extraordinary development of the muscular 
coat of the umbilical arteries, and denies the existence of other blood- 
vessels than the main channels in its structure. Professor Simpson thus 
resumes the result of his investigations on the structure of the cord and 
placenta:—“Into the composition of these parts no capillaries, vasa vaso- 
rum, lymphatics, nor nerves are found to enter; hence, in human anatomy, 
we have these organs forming a large mass, and weighing on an average 
about two pounds, presenting a type of structure resembling that of some 
of the inferior zoophytes.” I have sought very carefully with the best 
powers of the microscope for nerves in the umbilical arteries, and 
have witnessed no appearance which would give the least suspicion of 
their existence, but the muscular fibers have their typical character and 
micro-chemical reactions. They may be beautifully isolated by macera- 
tion in dilute nitric acid, and, not being associated with elastic tissue, pre- 
sent the appearance they offer in the minutest arteries of the adult. 9 
The arteries of the cord contract immediately on separation from its 
attachments, so that it is with difficulty that a liquid can be forced through 
them. In this state they appear like impermeable cords of a line in 
diameter. Hunter observed that they would retain this appearance for 
several days, till incipient decomposition produced complete relaxation. 
When relaxed completely, they are like flat bands of two lines in breadth, 
and transmit liquids in copious streams. The persistence of their irrita- 
bility, though most probably not greater than that of adult arteries, fits 
them for prolonged experimentation. 
1st. On the Influence of Different Degrees of Heat on the Caliber of the 
Blood-vessels. 
The current flowing through a piece of umbilical artery was gradually 
heated, and as the following degrees, measured by a delicate Centigrade 
thermometer held in the stream, were reached, the following quantities 
were discharged in periods of three minutes each. 
At 20 Centigrade, 68 Fahr. 3 fluid drachms. 
At 86 “ 4 “ “ 
At 91 “ 5| “ “ 
At 34° “ 93.2 “ 71 “ “ 
At “ 98.6 “ ' 11 “ 
At 46 “ 114.8 “ 5 fluid ounces. 
I have not determined the law of dilatation under different degrees 
of heat and varying rapidity of transition, but this series of observations 
proves, as did numerous others, that arterial dilatation is increased with 
elevation of temperature, and that the vascular irritability is most marked 
in the vicinity of blood-heat. An exceedingly interesting point is the 
limit of dilatation and the complete relaxation and paralysis of the muscular 
tissue at 115° Fahrenheit. This I have established by most careful ob- 
servations, and the proof that the same phenomenon occurs in living 
animals also, I have given in an article on sun-stroke in the Boston Med- 
ical and Surgical Journal for June, 1864. When the temperature of the 
blood in rabbits has been raised to this point, the blood-vessels of the ears, 
turgid with dilated vessels and rapidly circulating blood, refuse to con- 
tract under the influence of cold and galvanic currents; when this symp- 
tom manifests itself, death soon ensues. 
Water was heated to 55° Centigrade, and, as it cooled, portions of um- 
bilical artery at the temperature of the room were immersed in it, at 
intervals of two degrees of temperature and for a minute of time. At 10 
55° and 53° Cent., the artery became perfectly flaccid; at 51°, the flaccidity 
was not so complete, the artery possessed the slightest degree of tonicity; 
at 49°, the artery coiled up on immersion, and remained in a state of 
rigidity after it was withdrawn; at 47° it coiled up on immersion, but on 
exposure to the cold contracted more firmly ; at 45° and 43°, no marked 
contraction ensued during immersion, but followed its withdrawal and 
exposure to the cold. These experiments prove that what is true of the 
striated muscular fiber, holds good also with the non-striated fiber of the 
arteries, both becoming rigidly contracted and paralyzed by a sudden 
elevation of temperature to the vicinity of 115° Fahrenheit. 
In these experiments, no active dilatation could be perceived. The 
artery simply yielded to pressure from within, or to mechanical distention. 
Evidence that heat has the power of relaxing the muscular coat of the 
finest arterioles was gained by experimenting on whole organs with the 
defibrinated blood of the lower animals. When a column of blood, four feet 
in height, connected with the artery of an organ—a kidney, for example— 
could not force a single drop from the veins, it was sufficient to immerse the 
organ in water at or above 100° Fahr., to admit free circulation through 
its capillaries, the rapidity of which rose with the elevation of temperature. 
2d. On the Effects of Medicinal Substances on the Caliber of the Blood- 
vessels. 
The medicinal substances subjected to experiment were chosen from 
the class of stimulants and sedatives, as most likely to manifest a direct 
influence on the muscular coat of the blood-vessels. In Wood’s classifica- 
tion of the Materia Medica, the systemic stimulants proper are divided into 
the arterial, nervous, cerebral and spinal, and the systemic sedatives into 
the arterial, nervous and cerebral. Representatives of each of these 
classes were tested, and proof secured that many of them act directly upon 
the blood-vessels. 
1. The Arterial Stimulants, according to Wood, are capsicum, oil of 
turpentine, certain ammoniacal preparations, of which carbonate of 
ammonia is chief, and phosphorus. Of these, carbonate of ammonia was 
deemed most worthy of study, from its undoubted medicinal powers, from 
the interest it has excited in theories of uraemic convulsions, of the coagu- 
lation of the blood, and of the causation of a low grade of fevers. 
In one series of experiments with this substance to the liquid flowing 
steadily from the artery, at the rate of four and one-third fluid ounces every 
two minutes, the carbonate was added in the proportion of fifteen grains 
to the pint. The flow soon reached five fluid ounces in the same period, 11 
and as the ammonia, or a mono-carbonate, evaporated from exposure to 
the air in a thin stream at the temperature of 100° Fahr, (the liquid 
having been poured back into the upper reservoir after each observation,) 
the quantity discharged fell to three and one-third fluid ounces. On adding 
an additional fifteen grains, the quantity rose to four fluid ounces. Here 
the play of the artery, under the varying doses of the carbonate, proved 
that we were dealing with physiological irritability, and not with mere 
physical or chemical phenomena. 
To control these results and eliminate the influence shown by Poise- 
Ilille to be exerted by ammonia to hasten the current of liquid in inert 
tubes, arteries were immersed in solutions of the carbonate of different 
strength, the liquid flowing through them being the simple saccharine 
solution. An artery which discharged one and five-sixth fluid ounces 
per minute before it was suspended in a solution of the carbonate of 
the strength of a drachm to the ounce, after five minutes’ immersion, 
discharged sixteen ounces per minute. An artery which, before immer- 
sion, discharged two ounces per minute, after immersion for three? minutes 
in a solution of the strength of ten grains to the ounce, discharged eight 
ounces per minute. An artery which, before immersion, discharged two 
and one-sixth ounces per minute, after immersion for twenty minutes in 
a solution of the strength of two and a half grains to the ounce, discharged 
five ounces per minute. From the first experiment there resulted com- 
plete paralysis of the artery; from the others, relaxation merely, with con- 
servation of irritability. Although the proportions of the carbonate were 
greater than those of the medicinal doses to the amount of blood in the 
circulation, still the arteries are undoubtedly more sensitive in a living 
animal than they were in these experiments. 
The fact that ammonia possesses the power of relaxing the arteries hav- 
ing been proved, it remained to trace its influence upon the volume of the 
arteries, and the force and frequency of the pulse when administered as a 
remedy in disease. This study led me to several unexpected results. I found 
that 1 could administer thirty grains every fifteen minutes for an hour with- 
out the slightest influence on the pulse; that I could in no case produce its 
excitement, and that in several cases the result was its actual depression. 
It was strange that the medical authorities who testified to the stimulating 
properties of the sesqui-carbonate, when given in doses of ten grains every 
two hours, should have omitted to mention that it might be administered 
in doses of thirty grains every fifteen minutes, with no appreciable effect 
on the system. It was a disappointment to find the conclusions I had 
drawn from my experiments in the laboratory, falsified by further expert- 12 
meats in the wards. I had not taken into consideration that carbonate of 
ammonia in solution is decomposed, according to Wood, “ by most acids,” 
“and by most salts with excess of acid,” “by potassa, soda, and their car- 
bonates ; by lime-water and magnesia,” and “ by the soluble salts of lime ;” 
that the gastric juice contains free hydrochloric and lactic acids, and that 
this secretion is seen to be poured out abundantly when the stomach of one 
of the lower animals is touched through a fistulous opening by a rod dipped 
in an alkaline solution; that, should the carbonate escape decomposition 
by the acids of the gastric juice, the alkalies and their carbonates would 
meet it in the blood, and destroy it often, as rapidly as it should be ab- 
sorbed ; that, should the carbonate be absorbed more rapidly than it could 
be decomposed by the gastric juice and the blood, it would probably not 
enter the arterial blood at all, but that portion which continued to be 
volatile, would escape from the system by the lungs, as sulphuretted hydro- 
gen is known to do when sulphur-waters have been taken into the stomach. 
The systemic influence of the carbonate would therefore be that of a more 
stable compound of ammonia, as the muriate for example; its local influ- 
ence would be one of irritation to the stomach, if not sufficiently diluted, 
and perhaps one of the free ammonia in the lungs. After taking a drachm 
of the carbonate, I caused all the air I expired for fifteen minutes to pass, 
in fine bubbles, through a linen tissue, kept saturated with dilute hydro- 
chloric acid. The evaporated liquid yielded a notable amount of sal- 
ammoniac. As the linen had been previously soaked and washed in dilute 
hydrochloric acid, the ammonia could have had its source only in the 
expired air, and so large a proportion could not have been an ordinary 
physiological phenomenon. I concluded therefore that when large doses 
of carbonate of ammonia are taken, free ammonia escapes by the lungs. 
It is possible that the decided benefit with which the carbonate is admin- 
istered in certain pectoral diseases, is due to this cause. In the experi- 
ments of Frerichs on uraemia, the injection of carbonate of ammonia into 
the blood was followed by convulsions, and the abundant escape of ammo- 
nia from the lungs. The question of the amount of ammonia expired, 
after large doses of the carbonate, should be settled by competent chem- 
ical authority. 
The speedy precipitation of large and abundant crystals of the ammonio- 
magnesian or triple phosphate from the urina sanguinis, which, before the 
administration of the carbonate, had no such tendency, proved that an 
ammoniacal compound had found its way into arterial blood; but my ex- 
periments had shown that the stable ammoniacal compounds—the chloride, 
at least—had no influence in dilating the arteries, and thus the results of 13 
clinical observation and those of experiment were reconciled ; moreover, 
if I inspired for live minutes the air passing into a flask containing a solu- 
tion of carbonate of ammonia, the excitement of the pulse was immediate 
and very manifest—but so was the irritation of the lungs. 
That a general relaxation of the muscular tissue of the blood-vessels 
must produce those febrile phenomena called by physicians “ general 
stimulation,” can be shown to follow from well-known physiological laws. 
The inconsistencies of the nervous theory of fever have been acknowl- 
edged by some of our best pathologists, who still cling to the doctrine 
of Cullen. How they can explain the effects of counter-irritation by 
the admission that there is in tile body only a “ certain amount of 
nervous influence,” which when called to one part must forsake others, 
and yet trace to nervous influence the phenomena of fever, which they 
define as “a general disease affecting all the functions,” has always seemed 
to me incomprehensible. The truth is, that a general excitement of the 
system cannot be a nervous manifestation simply. If one sense is devel- 
oped or exercised, it is at the expense of the growth or activity of the 
other senses; the activity of the cerebrum calls off energy from the auto- 
matic nervous apparatus; pure nervous diseases are of a local character; 
all nervousness is non-febrile ; severe injuries affecting the nerves are not 
immediately followed by fever. These and other facts of the same bearing 
are too patent, one would think, to the daily observation of physicians, to 
permit them to lay much stress on the accepted nervous theory of fever. 
In all nosologies, the pyrexiae and neurotica form as distinct classes as 
nosological classification allows. 
The necessary result of the existence in the blood of a substance acting 
simply to relax the muscular coat of the blood-vessels would be, in the 
first place, an increase of pressure in the arterioles and capillaries, in 
accordance with a well-known law of physics. This has been shown by 
Bernard to be the fact in several local circulations by cardiometric experi- 
ments. He has shown also that wourara, injected into the arteries of the 
sub-maxillary gland, produces paralysis of the motor nerves of the blood- 
vessels, with consequent increased rapidity of the circulation and escape 
of the blood from the vein in jets, corresponding with the pulses of the 
heart.* Should these phenomena of paralysis be systemic, instead of local, 
general venous distension would ensue, did not the heart beat more 
actively and the lungs transmit the crowding blood more rapidly. But 
the chief stimulus to the rythmical action of the heart is its supply of 
blood. Even after the medulla oblongata has been severed, we can control 
* See Journal d’Anat. et de Physiol. 1864, p. 511. 14 
the action of the heart by withdrawing blood from the system, and inject- 
ing it again into the blood-vessels; can thus arrest its motion, and restore 
it to action ; or the same result can be effected by remitting or accelerating 
the movements of artificial respiration, thus diminishing or increasing the 
flow of blood to the heart through the lungs. The heart is the servant of 
the tissues and organs; it is from the capillary circulation mainly that its 
impulses are derived; hence, increased capillary circulation necessitates, 
when the links of the vital chain are still unbroken, increased action of the 
heart, and the flame of vital combustion may thus be fanned to fever heat. 
That the common properties of muscular tissue are affected in our most 
characteristic febrile disorders is seen4n the excessive prostration, muscu- 
lar pains and weakness; in the slipping down in bed, and in the muttering 
delirium (one whose energies find no muscular expression); in the difficulty 
of swallowing, while the clearness of the intellect shows cerebral activity 
not seriously disturbed; in the tympanitic condition of the bowels, and the 
oppressed respiration. The increased pressure in the capillaries is marked 
by epistaxis, h;emmorhage from the bowels, petechia?, and extravasations. 
After death from zymotic diseases, the softening of the organs generally, 
and particularly of those which are most vascular, is mainly due to the 
relaxation of the muscular tissue of the blood-vessels; is to these organs 
what the absence of cadaveric rigidity is to the limbs and trunk. The 
heart is found softened, not from a fatty degeneration, as I have repeatedly 
assured myself, but from a loss of tenacity of the muscular fibers entering 
into its composition. It shows the zymotic influence more than other 
striated muscles, because its unresting activity and rapid nutritive changes 
call for a full supply of blood, and receive a proportionate supply of its 
poison. 
A materies morbi in the blood, confined there by the membranes of the 
blood-vessels (as all membranes have the power of secerning), would be 
in closest contact with the muscular tunic of the smallest vessels, and 
would exert upon them its paramount influence; but this admission is by 
no means essential to the theory advanced. The muscular activity of the 
blood-vessels is in constant play and delicate movement of adaptation to 
the pressure of the blood and the demands of the tissues, so that a poison 
diffused through the system would make its influence manifest by a dis- 
turbance of what is so nicely balanced, and on a tissue of such active 
nutrition and delicate reactions. 
For these reasons, and abundant circumstantial evidence of their 
validity, which it would be tedious to detail, I would propose the fol- 
lowing definition of fever: An acute morbid activity of the general circa- 15 
lation and vital combustion, caused by the direct action of a blood-poison 
upon the muscular tissue of the blood-vessels. 
It would require more time than the session could afford to spare, were 
I to enter at length upon the consideration of the objections which might 
be presented to this view of the generation of fever: on this head I will 
therefore be brief. 
The School of Medicine at Paris teaches, through Monneret, that “ dis- 
turbance of the nervous system appears to be the cause of the lesion of 
calorification and of the other febrile phenomena. How would it be pos- 
sible to explain, in any other manner, the singular march which intermit- 
tents present, commencing and ending at fixed hours, and yielding with 
facility to sulphate of quinia. In the other pyrexite, specific causes appear 
to play the principal part, by acting on the nervous system. Everything 
leads to the admission that the vital forces, and the nervous system which 
is their support, are primarily affected. The study of the causes of the 
pyrexia? seems to us to furnish a solid support to this hypothesis. Accord- 
ingly we see sometimes a local lesion, as a thorn buried in the flesh, 
sometimes a septic liquid, the virus of variola, of vaccinia, of marsh 
miasm, or the spontaneous alteration of the blood, provoke the febrile 
movement. At another time, it is to the disorganization of an organ that 
must be attributed the intense fever, which ceases only with the life of the 
patient.” If it is on reasoning such as this that the hypothesis of the ner- 
vous origin of fever rests, its foundation is exceedingly insecure. How 
explain, says Monneret, in any other manner, the phenomena of intermit- 
tents? We would ask how the admission affords the least explanation? 
What recognized law of nervous action explains the commencement and 
cessation of intermittents at fixed hours, and their prevention by sulphate 
of quinia? Again, so far from the nervous system being the “support of 
the vital forces,” comparative anatomy, embryology, and teratology teach 
plainly that the nervous system is an efflorescence, an exalted term, a per- 
fection of organization, by no means fundamental to its manifestations of 
force. Again, “thorns buried in the tiesh” are ndt a common cause of 
fever, and the “disorganization of an organ” must inevitably load the 
blood with the products of its decomposition. The remainder of Mon- 
neret’s arguments are equally favorable to another hypothesis. 
Wood, while lending a guarded adherence to the nervous theory of 
fever, and the doctrines of Brown and Darwin, confesses their inadequacy 
to explain some of the most marked characteristics of the febrile state. 
He says, “Along with the diminished exercise of nervous function, is neces- 
sarily a diminution of all the functions dependent on it. We may thus 16 
partially explain the condition of the chill, but there is something more 
which we do not fathom; something, in which the chill of fever differs 
from other instances of nervous depression. Upon principles which have 
already been explained, the general prostration is succeeded by reaction, 
and the fever is thus established. But there is here also something more 
than reaction. There is the continued action of the cause—a diversified 
play of sympathies in one case, a widely prevailing influence from some 
unknown agent in another; and fever is not merely the resilience of the 
bowed-down system.” That “ widely pervading influence,” that “ some- 
thing more than reaction,” that “something more which we do not 
fathom,” is a direct influence upon the muscular tissue of the blood-vessels. 
Wood, in combating the doctrines of Cullen, says, “ there is no proof what- 
ever of the existence of spasm of the extreme vessels. On the contrary, 
in the cold stage, they are in a state of collapse from their inability to 
receive and circulate the blood, and in the hot stage the vessels them- 
selves are dilated, as is obvious from the fullness and redness of the sur- 
face.” Precisely what condition maybe meant here by “collapse from 
inability to receive and circulate the blood,” we will not stop to inquire, 
but will note merely the admission that impeded transmission of blood by 
the extreme vessels is a phenomenon of the cold stage, while their increase 
of caliber marks the pyrexia. Before the bearing of the properties of 
muscular tissue upon the explanation of the phenomena of fever had pre- 
sented itself, and while I was interested in merely tracing out the effect of 
remedies, I had recognized, as a purely muscular property, what has 
hitherto been attributed to nervous action, the contraction produced by 
the sudden application of agents capable of relaxing the muscular fibres. 
In speaking of the effects of immersion of an umbilical artery in water at 
different temperatures, I noted that an artery raised suddenly to a heat of 
120.2°, Fahrenheit*, manifested increased rigidity and firmer contraction; 
raised suddenly to 116.4°, Fahrenheit, it became somewhat contracted, but 
still more firm on exposure to the cold. Still, I had proved that a gradual 
elevation of temperature was attended by uninterrupted dilatation till 
the point of paralysis and complete relaxation was reached at 115°. I 
had noticed that on admitting suddenly the flow of a heated liquid into 
an artery the dilatation was preceded by a few minutes of contraction, and 
the same was true of the action of certain medicinal substances. The 
following series, taken from among ray notes made in the laboratory, pre- 
sents these facts in a clear light. The amount of a continuous flow from 
an artery was measured for successive periods of two minutes each. The 
temperature of the circulating liquid was 110°, Fahrenheit. 17 
The following are the amounts;— 
First period of two minutes, 3 fluid ounces. 
Second “ “ “ 2| “ “ 
Third “ “ “ > 21 " " 
Fourth “ “ “ 21 “ " 
Fifth “ “ “ 2| " “ 
Sixth “ “ “ 2f “ “ 
Seventh “ “ “ 3| “ “ 
Eighth k‘ “ “ 3i “ “ 
Ninth “ “ “ 31 " “ 
Tenth “ “ “ 4 “ “ 
Eleventh" “ “ 4 " “ 
Ilere carbonate of ammonia was added in the proportion of fifteen 
grains to the pint to the liquid in the upper reservoir. 
Twelfth period of two minutes, 5 fluid ounces. 
Thirteenth “ “ “ 5 “ “ 
Fourteenth “ “ “ 3| “ “ 
Fifteenth “ “ “ . “ 
Sixteenth “ “ “ 3| “ “ 
Seventeenth “ “ “ 3£ “ “ 
Eighteenth “ “ “ 3f “ “ 
Nineteenth “ “ “ 4 “ “ 
Twentieth “ “ “ 4 “ “ 
Twenty-first “ “ “ 4 “ “ 
The temperature of the liquid had fallen five degrees in the forty-two 
minutes that the experiment lasted, and mono-carbonate of ammonia was 
evaporating during the eighteen minutes following its appearance in the 
artery. 
That\this mode of action is not confined to the blood-vessels, was 
proved in the following manner: From the small intestine of an animal 
just killed I cut rings by transverse sections. These I adapted to an in- 
strument, by which the ring of intestine was maintained at such a degree 
of tension by one arm of a lever, to which was attached an elastic band, 
that the other, or long arm, would mark on the divided arc of a circle 
the slightest contraction or relaxation of the circular muscles of the in- 
testinal ring. On immersing the ring in water above blood-heat, the long 
arm of the lever always marked a short period of contraction previous 
to the continued relaxation, which period of contraction was shorter as 
the temperature was higher. Similar phenomena of contraction followed 18 
the immersion of the ring in solutions, which afterwards steadily dilated 
it. I found also that by successive increments of heat, as on several 
speedy withdrawals of the ring from the heated liquid after immersion, 
I could produce a more continuous contraction, from which at last the 
relaxation was marked and rapid. Should like phenomena occur in the 
arterioles of a living being, as the study of the circulation of the blood in 
transparent tissues would lead to believe, a poison thrown suddenly into 
the circulation, having the property of dilating the vessels, would at first 
produce their contraction or a stage of chill, while, if its admission were 
gradual, rigors would not appear. Or, successive increments of poison- 
ous action in the blood-vessels, would either produce contraction or 
hold them in a passive, unchanging condition, till at last sudden and wide 
dilatation would be accompanied by the explosion of febrile disorder and 
paroxysmal symptoms in their greatest intensity. We have here an ex- 
planation of the so-called accumulation of excitability, the sudden dis- 
charge of which results in various paroxysmal attacks, to which the 
known laws of the nervous system afford no clue; we have at least an- 
alogies in the demonstrated laws of muscular action. 
That the fever poison is always the same, or that the nervous system 
does not exert an important influence over febrile manifestations, no one 
will pretend. But that the cause of fever resides in, or acts through, the 
nervous system, is, from the preceding considerations, extremely im- 
probable. 
I would note also the looseness with which the terms stimulation, seda- 
tion, exaltation, and depression of vitality, are current in the profession. 
That the necessary consequences of paralysis, or impaired contractility of 
the blood-vessels, should be called stimulation, and the most complete dis- 
order of function be denominated exaltation of vitality, shows an inade- 
quacy or error in the interpretation of symptoms, the consequences of 
which must be exceedingly unfortunate. 
Assimilation, growth, and development are the results of stimulation 
rather than disassimilation, atrophy, and combustion, and an inflammatory 
affection which leaves an organ shrivelled and cirrhosed, or a fever which 
wastes the system, and leaves it vacillating between life and death, is cer- 
tainly not an exaltation of vitality. 
In conclusion, I would claim the privilege of presenting the further 
results of experiment in this direction in a future communication. THE BLOOD-VESSELS IN FEVER. 
“Theories,” says one of the most cautious of modern physiologists, 
“give to Science form and motion; serve to bind together facts which 
must be bound in bundles to be usefully employed ; guide and incite 
explorers in the way of discovery.” “Were a theory,” says Prof. Grove, 
“open to no objection, it would cease to be a theory and become a law; 
and were we not to theorize, or to take generalized views of natural 
phenomena until these generalizations were sure and unobjectionable— 
in other words were laws—Science would be lost in a complex mass of 
unconnected observations, which would probably never disentangle them- 
selves.” But, from a medical point of view, some justification may be 
desirable of apparent presumption in offering opinions in opposition to 
those of widely recognized authority. Fortunately, the question of the 
nature and causation of fever is, for one of such ancient date and high 
importance, peculiarly open to discussion. The testimony of George B. 
Wood, so long our highest authority in general pathology and thera- 
peutics, is, that “there cannot at present be said to be any prevalent 
doctrine of fever. Each individual has the grounds before him and 
judges for himself, and probably most persons, seeing a little truth and 
some error in every exclusive hypothesis, have selected a portion of each 
and formed a sort of composite opinion, of which even the old Gothic 
doctrine of the humoral pathologists constitutes a part.” ‘Into that 
composite opinion it seems to me necessary to introduce another element, 
one of pre-eminent importance, which has hitherto, as far as I am aware, 
been overlooked, or which it has been impossible, until recently, to fairly 
recognize. Moreover, it is not to mere clinical experience that we must 
look for a revelation of the laws of disease. The laws of chemistry 
were not discovered in blazing fires or crumbling rocks; the laws of 
hydrostatics and hydraulics were not revealed in torrents, tides, or 
ocean-currents ; nor those of pneumatics and electricity in winds, 
whirlwinds, and thunder-storms; much less could it be rationally ex- 
pected that the laws of pathology should be disclosed amid the much 
greater complexity and more multitudinous conflict of elements presented 20 
to the physician at the bedside of a diseased or dying patient. It is in the 
laboratory, and by artificially contrived experiments, that the clue has 
ever been spun and the torch lighted to guide through the labyrinths 
which hide the arcana of nature. It is to the recognition of this fact, 
with that other, that the true nature of an object of study is best 
determined by multiplying the points of view from which it is regarded, 
together with a general demand by the profession for a pathology which 
shall be something more than a descriptive catalogue of cases and speci- 
mens, that it is owing that those who are older in the laboratory than in 
clinical experience are heard with willingness in an assemblage of phy- 
sicians. To oppose the teachings of medical authority may seem un- 
gracious, and may, I am aware, prove disagreeable in proportion to the 
local sway of the authority opposed; but the trust of faithful study and truth- 
ful interpretation of the laws of organization is not therefore to be betrayed. 
The theory and definition of fever proposed in a former paper, were 
the direct and natural result of experimental research, and I deem fur- 
ther experimentation the only proper response to objections which admit 
of experimental refutation; but enough has already been gained to 
justify an endeavor to place what has been acquired in such a light as 
to show its legitimate bearing. By so doing, I shall also better respond 
to the purpose of arousing discussion, which dictated the announce- 
ment of the titles of papers to be presented for a number of successive 
meetings. 
The muscular tissue is one of unstable molecular composition, and of 
delicate reactions; it is but reasonable to expect it to be influenced by 
blood-poisons, or to suffer from impaired nutrition when that fluid is 
depraved. But I have proved by experimenting on blood-vessels devoid 
of nerves, that their muscular tissue is directly and functionally affected by 
the composition of the liquids transmitted through them, and that the 
same liquids exercise a similar influence upon blood-vessels which contain 
nerves. The presence of nerves does not in these instances interfere with 
the direct action on the muscular tissue. The experimental proof 
acquired, that substances which have the power of permanently dilating 
the blood-vessels will previously produce their contraction by a direct 
action on their muscular fibres, renders the intervention of the nervous 
system in the explanation of the succession of fever to a stage of chill 
unnecessary. The introduction of the nervous system into the theory is 
in violation of the first rule of philosophizing, which demands but one 
sufficient cause. The most characteristic and protracted febrile disorders 
of zymotic origin are ushered in and accompanied by symptoms which 21 
point directly to impaired nutrition of the muscular tissue throughout 
the body, and immediately after death from these disorders the viscera 
generally, and particularly those which are most vascular, present the 
characters offered by a cadaver after the rigor mortis of the blood-vessels 
has passed off: they are flabby, and, if abundant hemorrhage has not 
occurred, are gorged with blood. The heart is found softened, not by 
a fatty degeneration merely, but by a failure of nutrition of its muscular 
fibers; its unresting activity has called for an abundant supply of blood; 
but the blood has become a poison to muscular tissue, and the heart 
therefore shows the toxic influence more evidently than any other mus- 
cular mass. I will not detail the arguments of my former paper on this 
subject, but will endeavor to offer additional justification of the definition 
there given of fever. With the groups of symptoms denominated fevers 
I had nothing to do, but fever was there defined, “An acute morbid activ- 
ity of the general circulation and vital caused by the direct 
action of a blood-poison upm% the muscular tissue of the blood-vessels.'" 
Increased activity of the circulation is generally regarded as the funda- 
mental element in the febrile state, the remaining phenomena of fever 
being its natural results, or mere concomitants. With the words “ vital 
combustion ” I associate no theory of animal heat, but simply express the 
symptom from which fever derives its name. With reference to its 
causation, I anticipate the following objections:— 
1st. That the prevalent nervous theory of fever better explains the 
increased activity of the circulation. 
2d. That increased activity of the heart is sufficient to account for 
the phenomena of fever. 
3d. That the definition is too exclusive, in that both the muscular 
and nervous systems have a share in the production of every fever; or 
in that, while certain fevers show a direct influence upon the muscular 
tissue of the blood-vessels, others manifest no such influence. 
I. No nervous theory of fever is adequate to afford an explanation of 
febrile phenomena. 
Were the nervous theories of fever, those which take precedence of 
all others in the estimation of the profession, at all adequate to account 
for febrile phenomena, an opposing theory could hardly claim a notice. 
The shortcomings of the former would be attributed to the imperfection 
of our knowledge of nervous action rather than to a defect in the theory 
itself. There is, however, not only ample room, but a demand for an 
explanation more in accordance with the Increasing definiteness of our 22 
knowledge of the distinct powers and reactions of the different tissues 
and systems of the body. The fact that the activity of the nervous 
system is due to polar forces, forbids us to base a general disease upon its 
direct influence in ah portions of the system. The poles of a magnet can 
as readily be supposed to be diffused throughout the whole bar, as the 
nervous system to produce direct excitement of the circulation in every 
blood-vessel of the body at the same time. The nervous system being an 
apparatus of relation, it is not within its province to cause directly a 
general disease of circulation and nutrition. It is on this character of 
nervous action that depends the therapeutic method of revulsion. Re- 
vulsive measures owe their efficacy to the facts involved in the following 
statement of Wood, that “there is in the human system only a certain 
capacity of nervous action, and a certain amount of blood. When either 
the former or the latter is strongly directed to a particular part of the 
body, there is a tendency to its diminution elesewhere.” No one will 
pretend that a different system of nerves is involved in the disease and in 
the counter-irritation by which it is relieved; and no physician, who has 
been able to draw any substantial and well-grounded conviction from his 
medical experience, will allow his faith in the value of counter-irritation 
to be shaken: he must throw aside the nervous theory of fever should it 
be found to conflict with so solid a conviction. But those cases to which 
counter-irritation is least applicable are those in which the grade of fever 
is highest. Such cases are even aggravated by revulsive measures. If we 
have not learned to “bring the system to the blistering point,” by vene- 
section and antiphlogistic remedies, when high fever accompanies an in- 
flammation, it is not the fault of our teachers. Were the increased activity 
of the circulation in such cases due to nervous influence, the fever would 
be relieved by a concentration of nervous energy in the part counter- 
irritated, or at least diminished in proportion to that derivative influence, 
for there is in the system “ only a certain capacity of nervous action.” 
The counter-irritation may be severe, but the fever does not in the least 
abate. Idiopathic fevers likewise will run a steady course, in spite of 
endeavors to concentrate the blood and nervous energy in any particular 
pant of the body. They will likewise run their course in spite of power- 
ful (remedies directed to the nervous system, and exerting upon that 
system a full measure of their characteristic physiological influence. 
Could fever thus evade all the influences acting upon the nervous system 
if it had its immediate origin in that system ? But there are other and 
equally weighty arguments against such an admission. Bernard dis- 
covered that a persistent local hypertemia and elevation of temperature 23 
without inflammation—in other words, circumscribed febrile phenomena— 
would be produced in various parts of the system by section of the 
sympathetic nerve supplying the blood-vessels of those parts, and he 
traced these phenomena to a dilatation of the blood-vessels dependent 
on their muscular tunic. Whatever support this discovery may seem to 
lend to a nervous theory of fever, it must be remembered that it proves 
that elongation of the circular muscular fibers of the blood-vessels is one 
link in the chain of causation, and if it can be shown that a direct 
influence through the blood upon the muscular tissue better explains 
the phenomena of fever, the introduction of the nervous system into the 
problem is an unnecessary complication. But, in the experiments alluded 
to, increased heat and vascularity follow closely the section of the nerve; 
whereas, in cases of severe nervous injury, hours elapse before the fever is 
developed, which, when developed, bears no relation to the severity of 
the symptoms of collapse, and may be violent when there has been no 
marked shock or nervous depression. No pathologist has ever attempted 
to predict the gravity of a traumatic fever from the amount of injury 
recognized to have been sustained by the nervous system. Again, death 
from protracted febrile disorders, as typhoid and typhus fevers, leaves the 
nervous system in a state of integrity which contrasts strongly with the 
softened and disorganized condition of the vascular viscera of the thorax 
and abdomen; the brain and spinal cord are neither softened nor dis- 
colored, nor in an appreciable manner diseased in structure, as the direct 
result of the most protracted fatal febrile disease. I have carefully 
examined quite a number of such cases without being able to detect any 
appreciable lesion. There is, therefore, no proof that the nervous system 
is affected in the production of febrile disorder, while the proofs of im- 
paired muscular nutrition are very decided. 
II. Febrile phenomena cannot be explained by increased activity of the 
heart. 
Boerhaave and Broussais taught that increased activity of the heart 
was the immediate cause of fever. One of Broussais’ “Four Hundred 
and Sixty-eight Propositions” is, that “fever is always the result of an 
irritation of the heart, either primary or sympathetic.” That excitation 
of the heart is one link in the chain of causation is very evident; but 
that over-excitement of the heart is of itself sufficient to generate a fever, 
few will be found willing at the present time to admit. Without dilata- 
tions of the arteries and arterioles (for the true capillaries of a single 
elastic tunic are not contractile, and these only are capable of yielding 24 
to the force of the heart), the heart has little power to increase the 
activity of the circulation. In such vessels excess of pressure may 
produce varicosities, or give the vessel a beaded appearance, but the 
faculty of transmission of blood will not thereby be augmented. 
Pressure is a much less important element than calibre in determining 
the rate of flow in inelastic tubes like the finest arterioles. In experi- 
menting on< this subject, I obtained in two cases the following results: 
An inelastic tube, which discharged nine fluid drachms in thirty seconds, 
under a pressure of one foot of liquid, discharged thirteen and a half 
fluid drachms under a pressure of two feet; seventeen drachms under one 
of three feet; and twenty under one of four feet. A tube which dis- 
charged seventy minims in thirty seconds, under a pressure of one foot 
of liquid, discharged a hundred and ten minims under one of two feet; 
a hundred and forty-five under one of three feet; and one hundred and 
seventy under one of four feet. It required in these experiments about 
three times the pressure to double the rate of flow. But the pressure 
in the finest arterioles and capillaries varies within a very narrow pos- 
sible range. Bernard gives the following figures in proof of the narrow 
range of degrees of constant pressure within the arteries of animals of 
very different size. The fixed constant pressure in the carotid of a horse, 
a dog, and a rabbit, were respectively 110, 103, and 95 millimetres of 
mercury. The oscillations, however, due to the pulsations of the heart 
were much wider, being 65, 12, and 5 millimetres respectively; but even in 
the horse, whose disproportion in size to that of man is so great, the 
greatest momentary tension under the pulsation of the heart is little more 
than one-half of the constant pressure. In a dog, the constant pressure 
in whose carotid was 110 millimetres of mercury, and the maximum 
165, the opposite carotid was tied, when the constant pressure rose to 165, 
and the maximum to 200. The maximum momentary pressure in this 
extreme exaltation of tension was not double the normal minimum pres- 
sure. But the force of the heart is lost in the arteries as they approach 
the capillaries, and the possible variations of pressure are there still 
further reduced ; the heart’s energy is too far spent in overcoming the 
resistance to the flow of blood in the successive ramifications of the 
arterial tree, with their barriers of friction and anastomosis, to influence 
the inelastic tension of the circular fibers of the blood-vessels. The 
height to which a column of mercury is raised in a vein is at best but a 
small fraction of the pressure in the corresponding artery, when the 
valvular arrangement of the vein is not brought into play by the activity 
of the voluntary muscles. 25 
If, however, the diameter of a capillary tube be doubled, the quantity 
of liquid discharged under a given pressure will be sixteen times as great. 
If a capillary tube by dilatation become one-fourth larger, it will transmit 
considerably more than double the amount of blood (512 to 625). It 
is thus evident, on the simplest physical principles, how small a proportion 
of the increased activity of the circulation, from whatever cause arising, 
can possibly be due to increased activity of the heart, compared with the 
influence exerted by the increased calibre of the blood-vessels, as regu- 
lated by their muscular tunic. 
III. The nervous disorders presented by every ease of fever are secondary 
or coincident, not fundamental. 
That a poison in the blood, or an alteration of its composition which 
has the power to affect the nutrition and activity of the muscular tissue, 
would exert a direct influence on some portion of the nervous system 
also, is a very rational presumption; that the nervous system should feel 
and manifest the affection of the muscular system is inevitable: both 
these admissions are entirely consistent with the theory advanced, which, 
nevertheless, requires a direct influence on the muscular tissue of the 
blood-vessels as the fundamental element in every case of fever. The 
arguments from counter-irritation, and from the relational office of the 
nervous system, apply to all cases of fever, whatever may be their dis- 
tinctive peculiarities, and point to a common mode of generation inde- 
pendent of nervous origin. The nervous system is not constituted in 
dependence upon positive amounts of generally distributed force, but 
reacts to variations in amount and distribution. Its phenomena do not 
essentially vary in the robust and plethoric, and in those whom chronic 
disease has rendered almost exsanguined. A temperature of forty degrees 
to a hand at sixty is no more sensible than one of sixty to a hand at 
eighty. Hence the various forms of tolerance to which the nervous 
system may be subjected. Abnormal distribution to it of blood may 
produce the most violent symptoms, as in insanity, epilepsy, and eclampsy. 
So delicate is the reaction of the nervous system of the highest organisms 
to foreign substances reaching it through the blood, that the resulting 
nervous phenomena present the greatest variety—even idiosyncrasies, 
those disheartening nervous problems, are thus rendered possible. 
The material cause of the diseases known as fevers is of very various 
origin, and doubtless of very diverse molecular constitution. How dif- 
ferent the source of the poison in the simple irritative fevers, in inter- 
mittents and remittents, in yellow fever, in typhus and typhoid, and in 26 
the exanthemata! Yet the description of the symptoms which usher in 
one of these is applicable alike to all, and in our most authoritative 
treatises on special pathology the expressions, “general discomfort, weari- 
ness, and languor, deficiency of appetite, furred tongue, disordered taste, 
soreness or numbness of the limbs, pain in the back, headache, mental 
depression, irritability, want of sleep,” or their equivalents, form the com- 
mon tableau of prodroinata. How different this from the distinct and 
specific symptoms by which we recognize the very commencement of 
medicinal or morbid action on the nervous system ! Lastly, the fever formed 
defies all attempts at arrest, or essential modification, by remedies addressed 
to the nervous system. The cause of the fever may lie, indirectly, in severe 
mental strain, or in some overpowering sorrow; the cause may persist in all 
its force when the fever is aroused, and often happily removes the system 
from nervous sway, and saves a life which would otherwise fail to sustain 
the nervous tension. A blood-poison has been produced through the 
agency of the nervous system, which, by acting on the muscular tissue, 
has released the system from nervous control, and generated the fever. 
The admission of such an element is a necessity, for “fever is more than 
the resilience of a bowed-down system,” and is warranted by the fact 
that the production of vitiated fluids through nervous agency is a matter 
of not unusual observation. 
I have reserved till now the nearest approach to experimental demon- 
stration which I have been able to obtain, that in the fevers the muscular 
tissue is directly affected, in order to give the facts their due prominence. 
This was accomplished in the following manner:—Portions of umbilical 
arteries from a cord just divided were dissected out, as is easily done, 
and attached to ligatures-. Blood was then drawn by cupping from a 
patient suffering from typhus fever, either simple, or complicated with 
inflammation. The blood was defibrinated and placed in one or more 
test-tubes. Healthy blood was treated in the same manner, and the 
prepared portions of umbilical artery were suspended in the diseased and 
in the healthy blood, and exposed for a given time to a temperature of 
100° Fahrenheit. In each experiment, after an hour’s immersion, it 
was easily recognizable which portions of artery had been suspended 
in the febrile and which in the healthy blood, by the flaccidity, dis- 
coloration, and lack of vitality manifested by the former, and the healthy 
appearance and reactions of the latter. Such results as this are of more 
value than long and labored arguments, and will, 1 hope, serve as an 
excuse for shortcomings in that respect.