2. Sacar fruto del invernadero
3.8 Análisis Estadístico
58
were consider2.bly more prominent than those encountered by Kel la.way et al . (1940 ) ·:rhen using parenterally administered eps ilon toxi n . The uain
electro cardiogr<-::.phic change s 11:hi ch they described in intact sheep were
bradycardia and T wave inversion. In rabbit s they also recorded S-T seg-
nent displacement. The pre sencE: of r. ::;mall but fo.irly cons i s t ent fo ll in
he:::.rt ro. tE: in the animals recC;iving parenterally nd.Jaini s t ered toxin implies that there i s some increase in vagal tone U...'1(Ler the se conditi ons. On the
other hand the fact tha t the heart rato increas ed markedly in the animals
which received toxin of 0nt8ric origin implies that the eff,;ct on heart
rate of parenkro lly admini s tt;red toxin may , as Kclln.way et al . ( 1940 )
suggest, be the result of impurities in the toxin preparP..tion , and that
th0se are e i ther not .:.bsorbed from the intestine: under nornw.l circu...r:1s tances ,
or (';l se are removed from the blood as i t ps. s s e s through the liver .
Nevertheless epsilon toxin does appear t o hnve a pronounced direct
t:ffe c t upon the heart in all in toxi c�:, ted animal s. Tha �lterations in the S-T segment e.nd T wave of the ECG 1 s are of parti cular interest as these
portions o f the cyc le are consid8red to be asso ci
a
ted w i th the repolar i sa t i on of the myocardial fibre ; but i t i s more convenient to defer anyfurther discussion of the s e aspec ts of the el
e
ctrocardiograms until the morphological changes which occur in the nyo cardium have b e en described inChapter 9 .
Before leaving the presEmt chapter however i t i s o f intere st to
compare the ECG pa t terns obtained in the anima l s wh i c h re ce ived parenterally
c.: dmini s tered toxin with the gross lesions which have ·been di s cu s s e d s o far.
Of the four animal s in whi ch there was evidence of severe bradycardia or
incompl ete heart b l o ck , three showed severe pulmonary oedema with the lungs weighing 380 , 420 and 410 gre.ms respectively. Of the animals in
v:hich changes in cardiac rhythm were abs ent s ix did not have obvious lung
oedema , the lungs weighing 220 grams or l e s s in all instanc e s . These
relationships are not abs o lute however since one animal with severe lung
�
oedema did not show any evidence of conduction disturban•c and one animal
59 Conclusions
1 . The most prominent clinical s i gns of ep s ilon toxin intoxi cation in mi ce are neurological di sturbances including severe depres s i on ctnd convul
s i ons .
2 . No gros s ly de tectable l o s i ons oc cur in mice whi ch re c
e
ive l ow l o th2 l l evel s of toxin but pulmonary oedGrna occurs when high c oncentrations oftoxin are given.
3 .
Di fferences in the suscE::ptib i l i ty of mice and lambs to the toxin onthe be sis of absolute dosP.ge E�nll sus c: cp tibi l i ty to the devGl opment of pul
monc"lry oe dema imply th2 t there may be c. species difference i n thE: suscep
tibili ty of the capil lary endothelium to the action of e p s ilon toxin.
4. Some of the c lini co.l sign::: of in toxi cation in lanbs depend upon the
type of change produced in the t i s sue s . Dyspnoea only occurs if pulmonary
oederns devel ops . Signs of nC;:urologi cE'. l damage were present i n some
anim.e..ls only, suggesting tho. t not all field ca ses of ontero toxaer:1ia shorr
these signs.
5 . In the absence of pulnonary o o dema the most notabl e gro s s l e si ons in intoxi cated lambs , at the time of death, were fluid and fibrin in the
peric2.rdial sac and subendocardial haoi'lorrhages. The former may be asso cia ted ':ri th vascular damage in the s e rosc.l ve ssels and the latter wi th dis turbances in myocardi
a
l function .6 . Dis tinct al terations occur i n the e; l e c trocardiograms . The brady- cardi2. whi ch occurs when toxin i s arunini s tered parenter� l ly may b e due to
substance s other than eps i l on toxi n . Arrhythmias occur in a proportion
of the anima l s but the rr1os t cons i s tent changes are altera t i ons in the
depolarisati on and repolari sation pat terns of the ventri cular myocardium .
7 . The e l e ct_rocardiographic changes are only broadly related to the
60 CHAP TER 8 : THE HORPHOLOGICAL CHANGES PRODUCED I N TH:S CENTRAL
NER VOUS SYSTEM DURI NG CL.FER F.RINGEN S TYPE D EPS ILON TOXI N I NTOXI CATION
Many of the c linical signs o f e�terot oxae mia ar e r e f erab l e t o the c e ntral nervous s ys t e m and i t i s n o w appropri a t e t o pr o c e e d t o a c l o s er s t udy o f i t , s i n c e prev i o us worker s hav e d e s c r i b e d
morphological c hanges in the b r a i n s o f i n t oxi c a t e d animals.
Compr e h e n s i ve s tudi e s on the progr e s s i o n o f the l e s i ons whioh oc c ur in the b r ains of i n toxicated mi c e and lamb s have b e en pub l i s h e d b y Griner ( 1 96 1 a ) . On the basis o f the s e s tudie s , and the r es u l t s o f experime n t s where radi oac tive trac e r s were used t o d e t e c t al t e r e d v as c u lar permeability 1 ( Gr i n er 1 �6 1 b ) he sugges ted t h a t t h e early c hanges in the brain ar e due to brain o edema foll owing vasc ular damage pr oduc e d b y eps i l o n t oxin. On e of the c r i t e r i a used for
j ud g i n g the pr e s e n c e of o e de ma was t o tal brain wet w e igh t . Howev e r , in five o f the six pairs o f i n t ox i c a t e d dnd con trol lamb s , whic h h e us e d , t h e animal rec eiving t h e t oxin was als o heav i e r o n a body w e i gh t b asis. 0h ile Gre e n ( 1 966 ) s tates that the brain we t weigh t
and t o tal b odywe ights o f adu l t mice ar e u n c orrelated , brain w e igh t
i n this spe c i e s is highly h e r i tab le and varies b e tw e e n s trai n s ,
The b r ains o f f emale animals ar e he av ier in relation t o b odyweigh t than those o f males and t h e water c on t e n t o f th e b r ain i s also
s t a t e d t o be age depe nde n t a l tho ugh the decr ease w i th i n c r e asing age
is small . It was the r e f o r e c onsidered to b e advisable to de termine
the a c t ual water c on t e n t o f samp l e s o f brain t i ssue in all
quan t i ta tive e xp er iment s o n brain oede ma.
Although Griner ' s light mic r o s c opic s tudi e s hav e pr ovid e d use ful information on t h e development o f t h e l e s i on s in t h e b rain dur ing in toxi c ation , the f i n er morphologic al asp e c t s of brain o ed e ma
a r e b e s t examined i'ti th the e le c tron microscope . Muc h o f the
c onfusion ab out b rain o e d e ma as it oc curs experimen tally and in man ,
has b e en c lari f i e d b y u l tras truc t ur al s tudie s o f the c ondi ti on. For
examp l e Wechslere tal in Klatzo and S e it e lb e r ge r ( 1 967 ) , have s hown that , in gr e y ma tter , exc e s s fluid ac cumulates i n trac e l lularly w i t hin
. ernTJlC'yirig