REPARATOKY INFLAMMATION
IN ARTERIES. 4344
THE TONER
LECTURES.section,a blood-clot similar to d fell out from the position, L. Thisclot was adherent,
though
not very strongly, to the topof^", and
ithad no
lateral attachment whatever.On
a level withB
the enormously thickened intima, p', and thegrowing inner layers of themedia
aremore
or less blended.Large
granulations arisefromthistissue and project inward, entirel}^ obliteratingthe lumen. The}' oftenmeet
and unite, foi-ming a trabecular network with very smallnarrow
interstices through which flows the blood;
p"
consists of such a trabeculated mass.The
structure of the granulations themselvesis cellular, in fact identical with those granulations which form the plastic clot after the ordinary ligature, v.Capillary vessels
and
smallblood canals in the inner la^'er of themedia
and the thickened intima: theyare incommunica-
tion with the intertrabecularspaces; the latteropen into the
lumen
of the artery-,and
receive andreturn theirblood thence,e. Position of elastic limiting layer between the intima
and
media.Only
traces of this elastic layer, however, can be dis-coveredhere; immediately above
and
below the point of com- pression it is well defined.The
cellular portion of the tunica intimaisverymuch
thickened.Third
Series.— The
third series,consistingof afew prepa-rations where limited torsion had been performed
upon
the femoral arteries of dogs,showed
aprocess of healing similar in verymany
respects tothatdescribed for thesecond series.At
the pointwhere thearter}^was
seizedand
compressed b}' the limiting forceps,was
to be seen thesame growth
of the plastic clot springing mainly fromthe irritated intima, aswas
describedand
representedin Fig. 9.The
principal difference betweenthe preparationsfrom thetwo
series in questionwas
located inthe lower end of the arterial stump, andwas
due to themechanical differencebetween the operation for ligature as performed inthe modified way, and thatusuallj- followed while performing limited torsion. In tlic latter, if the operation isproperl}^done,
by means
of tlie twisting forceps, the external tunic of tlievesselisformed
into a kind of knot, so to speak, while the middleand
inner coats are separated from the adven-titiafor a slightdistance,
and
are curved inward, thus forming amore
or lessperfectvalve a small distance below the point of seizure by the limiting forceps.By
pressure of the limiting forceps the internal tunic of the arteryis rubbed together a little distance above the end of the arterial stump, as in tlieoperation for tlie second series. This is the point where the healing process is again
most
active,where
the granulations spring from the proliferating intima, and w^here,by
the union of thelatterand
the subsequent changes which have already been mentioned, thelumen
of the vessel is first permanently closed.In the space belowthe point of compression
by
thelimiting forceps (thatpart of thelumen
of the arteryincluded between the point of compression aboveand
the incurved walls below) therewas
thesame
fibrinous clot having a serpentine lamella- tion and showingno
signs of organization, and immediately belowit) thesame
accumulation of colorless cells represented atp
just abovethe ligature in Fig. 9.The
incurvedmedia was
earl}^infiltrated witha greatnum-
ber of cells, andthe twisted adventitia stillmore
abundantlyshowed
this infilti'ation.The
healing inthese casesseemed
to progresswith about thesame
rapidity asin cases formingthe second series.Fourth Series.— The
fourlh series of experimentswas
directed towardthe determination of the sequence of
phenom-
enaafter the flow of blood in nn artery has been arrestedby
the temporary nse of the needle.As was
previously stated, the third and fourthmethods
of flpplying acupressure were followed.The number
of preparations constitutingthis serieswas
alsosomewhat
limited.An
exmnination of the fewmade
has led to the conviction that the process of healingafter aeu-46
THE TOXER
LECTURES.piessure is very similar to thatwhich secures the obliteration of the ligated artery.
The
sectionsexamined show
that the blood coagula in all have been fashioned in accordance with thesame
general law previouslyenunciated for ligature,and
that there has been a similar althoughverymuch
lessmarked
increasein thecellsof the intima at the point of greatest irri- tation,whichin the thirdmethod
is atthe locus of theneedle.Fig. 10 represents a
thrombus
after acupresaure (third method), 36 hours old.Low
power.a. Adventitia. m. Media, n.Position ofneedle. 79. Plastic clot at the bottom, d. Stratified clot above, l. Portion of
lumen now
free;when
the sectionwas made
thiswas
occupiedby
a recent unstratified orhomogeneous
blood-clotwhich
fell outduring handling.
In the preparations obtained
by
acutorsion (or the fourth method), the chief differencefrom
the precedingwas
that the processes weremore
active. In all the preparations of this series theplastic clotseemed
to be the sole organizing agent, the blood coagulato beinertor passive.Fifth
Series.— The
fifthand
last seriesconsisted of afew preparations obtained by compressing, between thearms
of serre-fines, the femoraland common
carotid arteries ofgood
strong rats—
the pressure being continued fromtwo
to four hours. Insome
of these preparations therewas
evidence that the channel of the artery had been restored soon after removal of the pressure. In some, however, thelumen
of the vessel remained permanently occluded. Inthe latter the surfaces of the intima brought into contactby
the serre-fines remained adherent, and a blood and plasticcoagulum
similar to those seen after acupressureby
the thirdmethod
were observed.The
plastic clot here also played thesame
role as in the former series, but the inflammatory process, asmight
have been expected,was
even lessadvanced
than in the case of acupressure.111 concluding the discussion of tlie five series of experi-
ments
above related,let us again call attention to the almost unvarying uniformity throughout all of them, of apparently one method ofhealing; i.e., b}'means
of the organizationand
vancularizationof
thej)lO'Sticclot alone.Concerning the collateral circulation there is, as far as I
know,
no dispute. Since the timeof Porter it has beenAvell established that there aretwo
species of collateral circulation, adirectand
an indirect, which, however,may
both be present in thesame
instance.Respecting the lengthof time required forthe perfect estab- lishment of the collateral circulation, the following observation ma}' have
some
significance.A
loop of intestine of a curarized frogwas withdrawn
from the abdominal cavityand
placed under the microscope, so thatthe arteryrunning along theinnercurve of the gutwas
in thefield.
Numerous
small capillarieswere observed tocome
off from it
and
runaround
the intestine immediately beneath the serous covering. These capillaries gave offnumerous
branches which united with each other.The
bloodwas now
interrupted in its
wonted
course throughthe arteryhy
press- ing the point of a needleupon
the latter, about half waj^be- tween the places of departure oftwo
adjacent capillaries.Immediatel}' the portion of the artery
on
the distal side of the compressing needlebecame empty and
contracted for a littledistance; at thesame
time the proximal endcommenced
to dilate. Isochronous with this, the nearest capillary on the proximal side began rapidly to dilate; in the spaceof a few seconds the blood in it
went by
jerks,showing
thearterial im- pulse.A
few secondslater thelateral anastomosing branches alsobegan
to dilate rapidly. Later still, the first capillary branching from the arteryon
the distal side of the point of compression began to returnits blood into the artery, at first fclowly, thenmore
rapidly,and finnlly with an arterial iinpnlse.48
THE TONER
LECTUUES.By
this time (certainlynotmore
than twentj' seconds afterthe first interruption of the arterial current), the anastomosing capillaries whichhad
established the collateral circuit were nearly as wide as the artery itself,and
were beating quite as violently.The
arterial flowbeyond
this point did notnow seem
tobe atall affected.The
establishment of the collateral circulation in thefrog's tongue, after the experiment relatedsome
distance above, did not take place so rapidly, since at leastfifty seconds were necessaryforits free establishment."What is the origin of the cells which constitute the organ- izable plastic clot?
After thestudy of our preparations
we
haveno
doubtthat the great masses ofthem
are derived immediately from the endothelialand
othercell elements of the tunica intima,by
a process of proliferation excited partlyby
the irritationcausedby
the ligature,the needle, or-forceps,and
stimulated b}' theunwonted
supplyof nutrient material constantly retained with- in their reach, in consequence of the sluggishmovements
of thefluids of the blood.Whence come
those colorless elements which have been brought fromsome
distance by theblood current—
those bothof the plastic
and
of the fibrinous clots of athrombus
such aswe
have been considering?Let usconsiderfirstthemigrated leucocytes,
whose
presence in the plastic clot in considerablenumbers
I have previously mentioned,and
t©whose
agency Billroth and llindfleisch as- cribe, in agreat degree, that organization of thefibrinous clot whichthey believein.Do
theycome
directly through the walls of the vessel, ordo
theycome
principally,by way
of thearterial current,from
above thethrombus
? Bubnoff declares thatmany
of the white blood-corpuscles found in a bloodcoagulnm
after liga- ture of avein,have travelled directly through the vessel-wall.Billroth rei)eated the experiments of Bubnofl, and extended
them
to thrombosed arteries.He
admits, in a general v>ay, the conclusions of the latter, but while stating that he has found the vermilion granules in the midstof the blood-clot in the carotid arteiy of a rabbit, he sa^'s that they are free^i.e.,not contained within the
body
of leucocytes. Rindfleischalso acceptsBubnofTs
conclusions. Tschausoff has repeated the experiments of Bubnotf,and
has declared that he has been unable to confirm the observations of the latter. Durante, afteran elaborateseriesof experiments, contests the conclusions of Bubnoff{vide pp. 15, 16), as also do Corniland
Ranvier.Thus we
have seen that not only have the observations of Bubnoff concerning the source of the organizing elements of thethrombus
failed to receive exact confirmation by the ex- perimentsand
observations ofany
one of the previouslynamed
investigators, but that,on
the contrary, no less thanfive
most
excellent observers, after carefully repeatingand somewhat
extending his experiments, have flatlycontradictedhim
inmany
important particulars.It therefore seems to
me
that, in the face of these negative results and positive assaults, neither the observations and con- clusions of Bubnoff, respecting the migration and functions of the white blood-corpuscles found in thelumen
of the ligated vessels, northe theories of others basedthereon, should stand foronemoment.
We
are,then, forced to the conclusion thatif any leucocytes atall havewandered
into the clot, the}'could only havecome from
theblood in thelumen
of the artery above the throml)us.As
to the function of the leucocytes found in the blood or fibrinousclot, it is so nearly nil, aswe
havealready seen, that whatever itmay
be it cannot save that clot from inevitable destruction.As
towhether or not those leucocytes found in the plastic clothaveany
mission to perform, I haveno
factsto ofTer, and therefore refrain from advancingassumi)tions."We next iiupiire into the genesis of those colorless cells 4
50
THE TONER
LECTURES.which
may, by way
of the blood current, have travelled to thethrombus
fromsome
distance.The
question of the genesis of the colorlesscells of theblood has for 3'ears called forth themost
indefatigable efforts of themost
eminent microscopists,and
has taxed the genius of the greatest physiologists of the age.Yet we
are far from pos- sessingan entirely satisfactory solution of theproblemIt is,however, generallyadmitted that in the spleen, in the liver,in the lymphatic glands, and, according to some,in the red
marrow
of bones, the rate of increase of thesecellsismore
rapid than elsewhere. Ithas, consequently, been claimed that each of those organs has something special todo
with their generation. It hasalso been demonstratedby
Strikerand by
others that the stable cells of the connective tissuemay
physiologically give origin tocells which enter the lymphatic circulation,
and
which cannot,by any means
at presentknown,
be distinguished fromlymph
corpuscles.The lymph
corpusclesthemselves have been observed to in- creaseduring theirown
proper circulation, and it is generally admitted thatwhenever
the circulation is sufficiently slowedand oxygen
is present in sufficientquantity, their self-propaga- tionisby no means
infrequent.The
following obserA'ation constrainsme
to recognize an additional source of supply, especially very conisiderable dur- ing the existence of inflammation.Fig. 11 represents a capillary of the mesentery of a frog, nine hours inflamed
and
magnified threehundred
diameters, afterward amplified, e. Capillary walls. Z. Leucocytes or wandering cells, external to the walls, g. Cells of adventitia swollenand
granular. /. Capillary endothelia granularand
swollen, their prominentbelliesencroaching considerablyupon
thelumen
of thevessel.The
arrowindicatesthe direction of the blood current, a,<f, i. Colorless corpuscles adherent to the walls, d. Israther firmlybound
to the wall b}'means
ofREPARATORY
a
bud
penetrating the latter, i.A
corpuscle adherent atthe point of union oftwo
adjacent endothelial cells, k.An
un- attached white corpuscle. a.A
white corpuscle, adhering tightly to the upperend
of an endothelial cell {b).At
tliecommencement
of the observation, this cell (6)was
flatly ai)plied tothe capillary wall as theother endothelial cellsnow
are, but itsupper extremity
showed
the slightest possible sepa- ration from the lowerpointof thenextendothelial cell above.The
upperpoint ofthis cell (6) appeared a little thicker than that of its higher neighbor.The
blood currentwas
sluggish,and
atintervals interrupted. Occasionally for a fewmoments
the current
would move
on with considerable energy.At
the point of observation, besides tlie obstruction to the circu- lationby
the swollen endothelia, the currentwas impeded by
the adherent white corpuscles.The
relative position oftlie corpuscles
was
such that, at the timewhen
the currentwas
forced forward withsome
impetus, the points of the red blood disks went with considerablemomentum
against the chink, and wereviolentlyjammed
intothe angle formedby
the upper surface of the adherent white corpuscle (a)and
the surfaceof the endothelialcell above it. In theattemptto pass on, these redblood disksmust
perforcebend
around the white corpuscle (a).The
tendencj' of these forceswas
evidently to loosen andto pry outfrom
its bed the upper end of theendo- thelialcell (6).During
an energetic increase in the velocity of the current thiswas
actually observed to take place. After that, thenext violentmovement
of the blood current sufficed to detach the wholecell and tocarry it oft" in advance of the other elements.When
tliemovement
slowed again, itwas
observed that the place of former attachment of this cell (6)was
void of its endothelial covering. I have observed the above-describedphenomena
on oneother occasion.Xow any
onewho
carefully examines the course of cnpilla-52
THE TONER
LECTURES.ries inthe inflamedmesenteryof a frog will meet, atnot very infrequent points,with just such appearances of the interiorof thevessel as thedetachment of an epithelial cell will
go
far to explain the significance of. I confess that Iam
inclined to believe thatthisappearancewould
occurmuch more
frequently but that soon a white corpuscle possessing unusual viscosity, fasteningitselfthere,spreads outand fills the void. It will beremembered
that, a propos of theapex
of the forty-eight hour blood-clotof a ligatedartery,anumber
ofepithelioidcells pres- ent in theclotwere both describedand
figured.As
a possible explanation oftheir presence,we may
suppose that theymay
have been detached from the irritated intima at orabove the levelof their location intheclot.Once
admitting, in inflammations affecting the innerlining of bloodvessels,thisdetachmentof swollen andirritated epithe- lium, itmay
be claimed as a necessaryconsequence that those cellsmust
appear in appreciably increasednumbers
in the blood.Now
precisely this is found tobe true respecting the blood in the inflamedstump
of a ligated artery; on the other hand, ithas not yetbeen observed of the bloodinmore
general inflammations. Itmay
be affirmed respecting the lattercases that because the expected increase isnot apparent the theory has at once been placed hors de combat.But
does it necessarily follow that herein is an insupei-able objection? These swollen granular epithelial cells which are displaced from theirposition on the internal liningmembrane
of a vessel are in a state of irritation.
What
shouldhappen
to their shape after being set free in the blood current?Under
this condition undoubtedly their tendencywould
be toassume
a spherical outline, and, if they should remain sus-pended
sufficientlylong in the flowing blood,itis probable that every trace of their original formwould
be obliterated.Concerning thechanges which an endothelial cell