Jose Antonio Marin-Neto, Marcus V Simoes, Elias M .Ayres-Neto, J .Luiz Attab-Santos, L. Gallo Jr., Dalmo Souza Amorim, Benedito Carlos Maciel
S tu d ie s o f th e c o ro n a ry c irc u la tio n in
C h a g a s' h e a rt d ise a se
D i v i s i o n o f C a r d i o l o g y , D e p a r t m e n t o f I n t e r n a l M e d i c i n e , F a c u l d a d e d e M e d i c i n a d e R i b e i r i i o P r e t o , U n i v e r s i d a d e d e S i i o P a u l o - S i i o P a u l o , B r a z i lPathogenesis of chronic Chagas' heart disease m ay include various disturbances in the coronary circulation, that could be responsible for the m yocardial lesions seen in hum an hearts and in experim ental m odels of the disease. In this paper we critically
reviewed the anatom ical and functional abnorm alities described in chronic chagasic patients, pertaining to the so-called vascular pathogenetic theory of Chagas' disease. The epicardial coronary arteries are usually free of significant obstructive disease in nonselected groups of chagasic patients exam ined at autopsy or by coronary angiography. However, chagasic patients who were studied after an episode of acute m yocardial infarction, show the sam e patterns of atherosclerotic coronary artery disease seen in
the general nonchagasic population. Studies of chagasic patients with angiographically norm al coronary arteries, by several scintigraphy m ethods, revealed m yocardial perfusion abnorm alities which m ay be caused by the m icrocirculatory derangem ents
described in anim als experim entally infected with the T. cruzi. Since hypoperfusion has been detected in regions with norm al or m ildly im paired wall m otion, it is likely that the m icrovascular disturbances precede and m ay be a causative m echanism for the subsequent m yocardial dam age. W e speculate that hibernating ventricular areas m ay occur in chagasic patients, on the basis of the evidence gathered from these studies. Recent investigations of chronic patients with Chagas' disease and chest pain showed
attenuation of the vasom otor responses to physiological and pharm acological stim uli, in the epicardial coronary arteries.
UNITERM S: Chagas' disease. Coronary circulation. Acute m yocardial infarction.
INTRO DUCTIO N
D
e r a n g e m e n tsp o s tu la te d to o c c u ro f th ein c h a g a s icc o r o n a r y c ir c u la tio np a tie n ts ( 4 5 ,4 7 )w e r e s o o n a f te r th e n o s o lo g ic d is c o v e r y o f th e d is e a s e b y C a r lo s C h a g a s in th e b e g in n in g o f th is c e n tu r y . A f te rAddress for correspondence:
Jose Antonio Marin-Neto
Divisao de Cardiologia, Departamento de Clfnica Medica
Faculdade de Medicina de Ribeirao Preto
Universidade de Sao Paulo
Ribeirao Preto - SP .- Brasil - CEP 14049-900
th o s e e a r ly s tu d ie s m u c h k n o w le d g e w a s a c h ie v e d o n th e b a s is o f e x p e r im e n ta l e v id e n c e , th u s o r ig in a tin g th e s o -c a lle d v a s c u l a r t h e o r y o f C h a g a s ' d i s e a s e p a t h o g e n e s i s . S e v e r a l in d e p e n d e n t s tu d ie s in e x p e r im e n ta l m o d e ls o f T . c r u Z l in f e c tio n s h o w e d e v id e n c e o f c o r o n a r y m ic r o c ir c u la to r y d is tu r b a n c e s th a t w e r e th e o b je c t o f p r e v io u s r e v ie w ( 3 5 ) . T h e s e a b n o r m a litie s a r e b e lie v e d to c o m p o u n d w ith im m u n o p a th o g e n e tic m e c h a n is m s , a n d tr ig g e r C h a g a s ' m y o c a r d itis ( 3 6 ) .
T h e p u r p o s e o f th is p a p e r is c r itic a lly r e v ie w th e e v id e n c e o f f u n c tio n a l a n d a n a to m ic a l d e r a n g e m e n ts o f th e c o r o n a r y c ir c u la tio n in h u m a n C h a g a s ' d is e a s e , a s d e r iv e d f r o m s tu d ie s f r o m o u r a n d o th e r s ' la b o r a to r ie s .
IN VIVO
A N D
POSTMORTEM
S T U D IE S O F
T H E E P IC A R D IA L C O R O N A R Y
C IR C U L A T IO N
IN C H R O N IC C H A G A S '
D IS E A S E P A T IE N T S .
S tu d ie s o f th e e p ic a rd ia l c o ro n a ry c irc u la tio n in c h ro n ic c h a g a sic p a tie n ts h a v e b e e n p ro m p te d b y c lin ic a l m a n ife sta tio n s o f C h a g a s' d ise a se . T h u s, a su b sta n tia l p ro p o rtio n o f c h a g a sic p a tie n ts c o m p la in s o f c h e st p a in , fre q u e n tly w ith a n g in a -lik e c h a ra c te ristic s th a t re q u ire c a re fu l c o n sid e ra tio n o f c o ro n a ry d ise a se a s th e c a u sa tiv e m e c h a n ism (2 2 ,4 I ) . M a n y o f th e se p a tie n ts h a v e c o n c o m ita n t e le c tro c a rd io g ra p h ic a b n o rm a litie s, c o m p a tib le w ith e le c tric a lly in a c tiv e a re a s su g g e stiv e o f re g io n a l fib ro sis; it is a lso v e ry c o m m o n to h a v e c o n d u c tio n d istu rb a n c e s w ith p ro fo u n d S T - T c h a n g e s th a t lim it o n e 's a b ility to ru le o u t isc h e m ia e ith e r a t re st o r d u rin g stre ss (1 ,9 ,1 3 ,2 2 ). F in a lly , sim ila rly to c o ro n a ry h e a rt d ise a se , re g io n a l v e n tric u la r d y ssy n e rg y is c o m m o n in c h a g a sic p a tie n ts, e v e n in v e ry d ila te d h e a rts (4 ,1 4 ,2 3 ,2 4 ). T h is is a d istin c tiv e fe a tu re o f C h a g a s' h e a rt d ise a se , u se fu I to d iffe re n tia te it fro m p rim a ry d ila te d c a rd io m y o p a th y , b u t d iffic u lt to d istin g u ish fro m th e e ffe c ts o f c o ro n a ry h e a rt d ise a se .
N e c ro p sy o b se rv a tio n s in c h ro n ic c h a g a sic p a tie n ts' u su a lly sh o w m ild c o ro n a ry a th e ro sc le ro tic le sio n s, m a in ly in o ld e r p a tie n ts (2 2 ). H o w e v e r, th e a th e ro sc le ro tic in v o lv e m e n t is ra re ly se v e re e n o u g h to e x p la in th e e x te n siv e m y o c a rd ia l im p a irm e n t (4 3 ,4 4 ). T h e se o b se rv a tio n s w e re c o rro b o ra te d b y se v e ra l in d e p e n d e n t stu d ie s u sin g c o ro n a ry a n g io g ra p h y in C h a g a s' h e a rt p a tie n ts (4 ,9 ,1 4 ,2 3 ).
O n e in v e stig a tio n in a u to p sie d c h a g a sic p a tie n ts c o rre la te d th e p re v a le n c e o f th e c h a ra c te ristic a p ic a l a n e u ry sm w ith th e h e a rt w e ig h t, a n d th e re la tiv e m y o c a rd ia l d istrib u tio n o f b o t~ c o ro n a ry a rte rie s (2 7 ). T h e fin d in g s o f th is in v e stig a tio n su p p o rte d th e c o n c lu sio n th a t u n fa v o ra b le p e rfu sio n c o n d itio n s p re v a ile d in th e a p ic a l re g io n o f th e h e a rt o f c h a g a sic p a tie n ts, th u s p ro v id in g a n isc h e m ic b a sis fo r th e a p p e a ra n c e o f th e a p ic a l a n e u ry sm .
F u rth e r e v id e n c e w a s o b ta in e d fro m h u m a n n e c ro p sy stu d ie s, sh o w in g stru c tu ra l v a sc u la r d isa rra y in th e le ft v e n tric le o f c h a g a sic p a tie n ts (1 0 ,1 5 ,4 4 ). T h e se a lte ra tio n s a re lik e ly to b e c a u se d b y in fla m m a to ry v a sc u la r c h a n g e s, le a d in g to re p a ra tiv e fib ro sis, a n d c o rre sp o n d to th e le sio n s d e sc rib e d in a n im a ls e x p e rim e n ta lly in fe c te d w ith th e
T.
cruzi
(2 1 ,3 2 ). In sp e c ia l, th e v a sc u litis d e te c te d in th e a p ic a l re g io n w a s im p lic a te d in th e g e n e sis o f th e a p ic a l a n e u ry sm , p re c e d in g th e a p p e a ra n c e o f th is le sio n in 3 0 % o f th e c h a g a sic h e a rts (1 0 ). H o w e v e r, c o ro n a ry v a sc u litisS a o P a u lo M e d ic a l J o u r n a l/R P M 1 1 3 ( 2 ) M a r /A p r 1 9 9 5
w a s n o t fo u n d b y o th e r in v e stig a to rs, in n e c ro p sy stu d ie s a n d in a n im a l m o d e ls o f th e
T.
cruzi
in fe c tio n (7 ,1 1 ). In th e la tte r stu d ie s, e sse n tia lly a ll th e m o rp h o lo g ic a l a n d m ic ro sc o p ic le sio n s u su a lly se e n in h u m a n C h a g a s' d ise a se w e re re p ro d u c e d in th e e x p e rim e n ta l m o d e l, in c lu d in g th e . a p ic a l a n e u ry sm (1 1 ,3 8 ). T h e se stu d ie s a lso d e sc rib e d tw o a d d itio n a l p a th o lo g ic a l a sp e c ts: a ) o c c lu siv e p ra te le t th ro m b o sis o f th e e p ic a rd ia l a n d in tra m u ra l c o ro n a ry m ic ro v a sc u la tu re (3 8 ); b ) h isto c h e m ic a l e v id e n c e o f fo c a l m y o c a rd ia l h y p o x ic le sio n s (3 7 ).A n o th e r
postmortem
stu d y sh o w e d in c re a se d v o lu m e tric c a p a c ity o f th e c o ro n a ry c irc u la tio n (v e sse l d ia m e te r> 4 0 1-1), in c h a g a sic p a tie n ts, a s c o m p a re d w ith n o rm a l c o n tro ls a n d h y p e rtro p h ic p a tie n ts (3 3 ). In th is in v e stig a tio n n o b e tte r p e rfu sio n c o n d itio n s w e re im p lie d a s a sso c ia te d w ith th e e p ic a rd ia l v a so d ila ta tio n th u s su g g e ste d . T h e c o ro n a ry v a so d ila ta tio n w a s p o stu la te d to d e p e n d o n stim u la tio n o f th e a lp h a a d re n e rg ic re c e p to rs, th a t w o u ld b e u n o p p o se d b y p a ra sy m p a th e tic d e n e rv a tio n . T h e re fo re , th e re su lts o f th a t in v e stig a tio n w e re in te rp re te d a s su p p o rtin g th e n e u ro g e n ic th e o ry o f th e C p a g a s' d ise a se c a rd io m y o p a th y (3 3 ). T h e u n d e rly in g p a th o g e n e tic m e c h a n ism w o u ld b e th e im p a irm e n t o f th e a u to n o m ic c o n tro l o f th e c o ro n a ry c irc u la tio n . H o w e v e r, th e re a l ro le o f th e a lp h a a d re n e rg ic re c e p to rs in th e c o n tro l o f th e c o ro n a ry e p ic a rd ia l c irc u la tio n re m a in s to b e d e fin e d . M o re o v e r, it w a s d istu rb in g to se e th a t im m e d ia te ly p re c e d in g th a t re p o rt (3 3 ), c le a r e v id e n c e o f c a rd io m y o p a th y a n d c o ro n a ry v a so c o n stric tio n c a u se d b y in fu sio n o f c a th e c o la m in e s w a s p u b lish e d (4 2 ). O f sig n ific a n c e , su c h d e le te rio u s e ffe c ts w e re b lo c k e d b y sp e c ific a lp h a re c e p to r a n ta g o n ists (4 2 ).A N A T O M IC A L S T U D IE S O F T H E
C O R O N A R Y C IR C U L A T IO N
IN C H A G A S IC
P A T IE N T S A F T E R A C U T E M Y O C A R D IA L
IN F A R C T IO N
T h e re h a v e b e e n sp a rse re p o rts o f c h a g a sic p a tie n ts w h o h a d a n e p iso d e o f a c u te m y o c a rd ia l in fa rc tio n , w ith p e rv io u s c o ro n a ry a rte rie s re v e a le d b y a n g io g ra p h y o r a u to p sy stu d ie s (2 9 ,4 6 ). A m o n g th e v a rio u s p a th o p h y sio lo g ic a l h y p o th e se s su g g e ste d in th o se re p o rts to e x p la in th e fa c t, m o st fa v o re d c o ro n a ry e m b o lism w ith sp o n ta n e o u s re c a n a liz a tio n o r c o ro n a ry sp a sm , a s th e lik e ly m e c h a n ism s. T h is is sim ila r to th e p re d o m in a n t th o u g h ts a b o u t m y o c a rd ia l in fa rc tio n w ith a n g io g ra p h ic a lly n o rm a l c o ro n a ry a rte rie s in n o n c h a g a sic p o p u la tio n s.
1 -
Studies of the regional myocardial perfusion.
F U N C T IO N A L S T U D IE S O F T H E
C O R O N A R Y C IR C U LA T IO N IN P A T IE N T S
W IT H C H R O N IC C H A G A S ' D IS E A S E
T able 1
R esults of quantitative coronary angiography in chagasic and nonchagasic patients w ith acute m yocardial infarction from 1981 to 1988 at the
M edical S chool of R ibeirao P reto, U S P C hagasic N onchagasic
T h e p i o n e e r i n v e s t i g a t i o n s o f E . K u s c h n i r a n d c o -w o r k e r s ( 1 6 ,1 9 ) , u s i n g 8 6 - r u b i d i u m , s h o w e d a b s o l u t e r e d u c t i o n o f r e g i o n a l e f f e c t i v e m y o c a r d i a l f l o w i n C h a g a s ' h e a r t p a t i e n t s . T h e f l o w r e d u c t i o n , o f m a g n i t u d e c o m p a r a b l e t o t h a t e x h i b i t e d b y n o n c h a g a s i c p a t i e n t s w i t h p r o v e n c o r o n a r y o b s t r u c t i o n , w a s o b s e r v e d b o t h a t b a s e l i n e ( 1 9 ) , a n d d u r i n g e f f o r t ( a l t h o u g h l e s s m a r k e d l y ) ( 1 6 ) .
5 6
2 1 9
17 (7.8% )
39
26
*2 (7.7% )
*A M I = acute m yocardial infarction
U n d e r t h i s h e a d i n g a h e t e r o g e n e o u s g r o u p o f i n v e s t i g a t i o n s i s c o m p r i s e d , a i m i n g a t t h e d e t e c t i o n o f o b j e c t i v e e v i d e n c e o f m y o c a r d i a l i s c h e m i a , a s w e l l a s o f r e g i o n a l v e n t r i c u l a r d y s f u n c t i o n a s a c o n s e q u e n c e o f i s c h e m i a , i n C h a g a s ' h e a r t p a t i e n t s . A l s o i n c l u d e d i n t h i s t o p i c a r e t h e m o r e r e c e n t s t u d i e s o f t h e c o r o n a r y r e a c t i v i t y t o p h y s i o l o g i c a l a n d p h a r m a c o l o g i c a l s t i m u l i .
T otal of patients w ith A M I N um ber w ith coronary
angiography N orm al coronaries
a n g i o g r a p h i c a l l y n o r m a l c o r o n a r y a r t e r i e s , w h i l e 5 4 % o f t h e c a s e s p r e s e n t e d m u l t i v a s c u l a r l e s i o n s .
T h e s e o b s e r v a t i o n s a r e c o n s i s t e n t w i t h t h e c o n c e p t t h a t , s i m i l a r l y t o w h a t i s c h a r a c t e r i s t i c f o r n o n c h a g a s i c p a t i e n t s , a c u t e m y o c a r d i a l i n f a r c t i o n i s c a u s e d b y a t h e r o s c l e r o t i c c o r o n a r y i n v o l v e m e n t i n c h r o n i c c h a g a s i c i n d i v i d u a l s .
H o w e v e r , i t i s n o t e w o r t h y t h a t i n t h e l a s t d e c a d e s a n i n t e n s e p r o c e s s o f p r o g r e s s i v e u r b a n i z a t i o n o c c u r r e d r e g a r d i n g t h e p r e v i o u s l y c o u n t r y - b a s e d c h a g a s i c p o p u l a t i o n . A s a c o n s e q u e n c e , p r o f o u n d l i f e s t y l e m o d i f i c a t i o n s l e d t o e x p o s u r e o f c h a g a s i c p a t i e n t s t o t h e s a m e r i s k f a c t o r s f o r a t h e r o s c l e r o s i s t h a t a r e o p e r a t i v e i n t h e n o n c h a g a s i c p o p u l a t i o n . T h e r e f o r e , i t b e c a m e p l a u s i b l e t o a s s u m e t h a t c o r o n a r y a t h e r o s c l e r o t i c d i s e a s e m i g h t n o t b e i n f r e q u e n t l y f o u n d i n c o n c o m i t a n c e w i t h C h a g a s ' h e a r t d i s e a s e . T h i s c o n c e p t i s s u p p o r t e d b y t h e i n d i r e c t e v i d e n c e t h a t o f 1 3 6 c h a g a s i c p a t i e n t s w h o w e r e s u b m i t t e d t o c a r d i a c c a t h e t e r i z a t i o n b e c a u s e o f a n a s s o c i a t e d c a r d i o p a t h y , h e m o d y n a m i c a l l y s i g n i f i c a n t c o r o n a r y o b s t r u c t i o n s w e r e f o u n d i n 5 1 p a t i e n t s ( 3 7 % ) ( 1 2 ) .
A r e t r o s p e c t i v e s t u d y i n o u r i n s t i t u t i o n ( 5 ) d i r e c t l y t e s t e d t h e h y p o t h e s i s t h a t t h e a s s o c i a t i o n o f m y o c a r d i a l i n f a r c t i o n a n d n o r m a l c o r o n a r y a r t e r i e s w o u l d b e m o r e f r e q u e n t i n c h a g a s i c a s c o m p a r e d t o n o n c h a g a s i c p a t i e n t s . T h e c l i n i c a l f i l e s , a n d n e c r o p s y r e p o r t s o f 3 9 5 c o n s e c u t i v e p a t i e n t s p r e s e n t i n g w i t h a c u t e m y o c a r d i a l i n f a r c t i o n f r o m
1 9 8 1 t o 1 9 8 8 w e r e a n a l y z e d . I n a l l c a s e s t h e d i a g n o s i s o f i n f a r c t i o n w a s c o n f i r m e d b y e l e c t r o c a r d i o g r a p h i c a n d / o r e n z y m a t i c c r i t e r i a . C o r o n a r y a n g i o g r a p h i c f i n d i n g s w e r e a n a l y z e d b y c o m p u t e r a s s i s t e d d e t e c t i o n o f v a s c u l a r e d g e s , a n d s u b s e q u e n t q u a n t i t a t i o n o f t h e s t e n o s e s . O f t h e 3 9 5 p a t i e n t s w i t h m y o c a r d i a l i n f a r c t i o n s t u d i e d , 3 9 ( 9 .9 % ) h a d a l s o a d i a g n o s i s o f C h a g a s ' d i s e a s e c o n f i r m e d b y s e r o l o g i c a l t e s t s . I n 2 6 o f t h e m , t h e c o r o n a r y a n a t o m y w a s d e t e r m i n e d b y a n g i o g r a p h y a n d / o r a u t o p s y . I n t h e n o n c h a g a s i c p o p u l a t i o n w i t h a c u t e m y o c a r d i a l i n f a r c t i o n t h e c o r o n a r y a n a t o m y w a s k n o w n i n 2 1 9 p a t i e n t s . T h e f r e q u e n c y o f n o r m a l c o r o n a r y a r t e r i e s w a s s t a t i s t i c a l l y c o m p a r a b l e f o r b o t h g r o u p s : 2 i n 2 6 ( 7 .7 % ) a n d 1 7 i n 2 1 9 ( 7 .8 % ) r e s p e c t i v e l y f o r t h e c h a g a s i c a n d n o n c h a g a s i c g r o u p s . ( T a b l e I).T h e d i s t r i b u t i o n o f h e m o d y n a m i c a l l y s i g n i f i c a n t s t e n o s e s ( > 5 0 % o f l u m i n a l d i a m e t e r n a r r o w i n g ) i n t h e c h a g a s i c p o p u l a t i o n s h o w e d u n i v a s c u l a r i n v o l v e m e n t i n 3 8 % , a n d m u l t i v a s c u l a r i n 5 3 % o f p a t i e n t s . T h e m y o c a r d i a l a r e a o f i n f a r c t c o r r e s p o n d e d t o t h e l e s i o n i n t h e c u l p r i t c o r o n a r y a r t e r y i n a l l c a s e s , a n d n o a n t h r o p o m e t r i c , c l i n i c a l , r i s k f a c t o r d i s t r i b u t i o n o r i n -h o s p i t a l e v o l u t i o n c h a r a c t e r i s t i c s w e r e f o u n d t o d i s c r i m i n a t e b e t w e e n t h e t w o g r o u p s o f p a t i e n t s . T h e p r e v a l e n c e o f c o r o n a r y a r t e r i e s w i t h n o d e t e c t a b l e l e s i o n s f o u n d i n t h i s s t u d y , f o r b o t h t h e c h a g a s i c a n d n o n c h a g a s i c p a t i e n t s i s s i m i l a r t o t h a t r e p o r t e d f o r n o n s e l e c t e d p o p u l a t i o n s i n t h e l i t e r a t u r e , o f 6 % ( 3 1 ) .
T h e s e f i n d i n g s w e r e c o r r o b o r a t e d b y t h o s e r e p o r t e d f r o m a n o t h e r i n s t i t u t i o n ( 3 4 ) , w i t h 1 3 c o n s e c u t i v e c h a g a s i c p a t i e n t s c a t h e t e r i z e d d u r i n g t h e a c u t e p h a s e o f a n a c u t e m y o c a r d i a l i n f a r c t i o n . O n l y 1 p a t i e n t ( 8 % ) h a d
T h e p e rfu s io n d is tu rb a n c e s w e re a ls o d e te c te d u s in g 2 0 I-th a lliu m a t re s t (3 9 ), a n d d u rin g e x e rc is e (2 8 ), in c h ro n ic c h a g a s ic p a tie n ts . In th e la tte r in v e s tig a tio n , fix e d p e rfu s io n d e fe c ts d e te c te d in th e a p ic a l re g io n o c c u rre d in 3 7 % o f th e p a tie n ts w ith th e c a rd ia c fo rm a n d in 2 5 % o f th e p a tie n ts in th e in d e te rm in a te p h a s e o f C h a g a s ' d is e a s e . T h e fix e d p e rfu s io n d e fe c ts w e re in te rp re te d a s p ro b a b ly c o rre s p o n d in g to lo c a liz e d fib ro s is in th e ty p ic a l a p ic a l re g io n , c o m m o n ly le a d in g to a n e u ry s m s in C h a g a s ' d is e a s e p a tie n ts (2 8 ).
T h e o c c u rre n c e o f re g io n a l p e rfu s io n d e fe c ts in c h a g a s ic p a tie n ts a t s e v e ra l s ta g e s o f th e d is e a s e w a s c o n firm e d b y o th e r in d e p e n d e n t in v e s tig a tio n s , u s in g 2 0 1 -th a lliu m (1 3 ,2 3 ), o r 9 9 m -te c h n e tiu m la b e lle d s e x ta m ib i (6 ). In a d d itio n to th e fix e d d e fe c ts a lre a d y m e n tio n e d , th e s tu d ie s w ith 2 0 I -th a lliu m s h o w e d p e rfu s io n d is tu rb a n c e s o c c u rrin g o n ly d u rin g s tre s s (re v e rs ib le ) o r a s re v e rs e re d is trib u tio n (p a ra d o x d e fe c ts ) (2 3 ). T h e re v e rs ib le p e rfu s io n a b n o rm a litie s s u g g e s te d th a t s tre s s -in d u c e d is c h e m ia c o u ld o c c u r in C h a g a s ' d is e a s e p a tie n ts . T h e p a ra d o x d e fe c ts , d e te c te d in 6 1 % o f th e p a tie n ts , w e re c o m p a tib le w ith d is tu rb a n c e s a t th e s a rc o le m m a l le v e l, p o s s ib ly d u e to im p a irm e n t o f c a p a c ity to re ta in th e tra c e r d u rin g th e re s t p h a s e o f th e s c in tig ra p h ic s tu d y (2 3 ).
In a re c e n t s tu d y w e u s e d a n s p e c ific m a rk e r o f re g io n a l m y o c a rd ia l flo w , w h o s e d is trib u tio n is in d e p e n d e n t o f th e m e ta b o lic p ro p e rtie s o f th e s a rc o le m m a (2 5 ). H u m a n a lb u m in m ic ro s p h e re s la b e lle d w ith 9 9 m -te c h n e tiu m w e re in je c te d in th e le ft v e n tric le o f 1 8 c h a g a s ic p a tie n ts s u b m itte d to c o ro n a ry a n g io g ra p h y b e c a u s e o f re c u rre n t s e v e re c h e s t p a in . T h e s c in tig ra p h ic d is trib u tio n o f th e m ic ro s p h e re s w a s a s s e s s e d in th e th re e p la n a r s ta n d a rd v ie w s , a llo w in g th e a n a ly s is o f 7 s e g m e n ts p e r p a tie n t fo r b o th p e rfu s io n a n d re g io n a l w a ll m o tio n (T a b le 2 ).
A ll p a tie n ts h a d a n g io g ra p h ic a lly n o rm a l c o ro n a ry a rte rie s a n d th e m e a n le ft v e n tric le e je c tio n fra c tio n w a s 5 2 ::t 1 2 . A t le a s t 1 p e rfu s io n d e fe c t w a s d e te c te d in a ll p a tie n ts . T e n o f th e m h a d > 3 a b n o rm a l s e g m e n ts (F ig .
I ). T h e n u m b e r o f re g io n a l p e rfu s io n d e fe c ts p e r s e g m e n t, a n d th e re s p e c tiv e w a ll m o tio n p a tte rn a re fo u n d in T a b le
2 .
T h e re s u lts o f th is in v e s tig a tio n le a d to th e c o n c lu s io n th a t tru e p e rfu s io n . d e fe c ts d C ?o c c u r in c h ro n ic c h a g a s ic p a tie n ts . T h e d e fe c ts a s s o c ia te d w ith a k in e s is o r d y s k in e s ia a re p re d o m in a n t in th e a p ic a l re g io n , a n d m a y c o rre s p o n d to lo c a l fib ro s is . O n th e o th e r h a n d , th e p e rfu s io n d e fe c ts fo u n d in z o n e s w ith p re s e rv e d w a ll m o tio n o r w ith m ild h y p o k in e s is , a re lik e ly to b e c a u s e d b y m ic ro v a s c u la r d is tu rb a n c e s , a s th e e p ic a rd ia l c o ro n a ry c irc u la tio n is e s s e n tia lly n o rm a l in th e s e c h a g a s ic p a tie n ts (2 5 ).
T a b le 2
N u m b e r o f p e rfu s io n a l d e fe c ts p e r s e g m e n t, c o rre la te d to th e re g io n a l w a ll m o tio n p a tte rn , in c h a g a s ic p a tie n ts in je c te d w ith 9 9 m -te c h n e tiu m
m ic ro s p h e re s .
A I A p S e p P I A P
N o rm a l/
H y p o k in e s is 6 5 6 3 8
A k in e s is /
D y s k in e s ia 0 1 5 2 0 0
S e g m e n t a n a ly s is : a n te ro la te ra l (A I), a p ic a l (A p ), in fe rio r
(I), s e p ta l (S e p ), p o s te ro la te ra l (P I), a n te rio r (A );
p o s te rio r (P ).
F ig u re 1 - P la n a r m y o c a rd ia l s c in tig ra p h y fo llo w in g le ft v e n tric u la r in je c tio n o f 9 9 m -te c h n e tiu m la b e lle d m ic ro s p h e re s , in a c h ro n ic c h a g a s ic p a tie n t w ith m a rk e d c h a m b e r d ila ta tio n . H y p o p e rfu s io n is s e e n in th e la te ra l p ro je c tio n , in th e a p ic a l (s h o rt a rro w ) a n d h ig h p o s te rio r (lo n g a rro w ) re g io n s .
2 -
Studies of the relation between regional perfusion
and
contraction in Chagas' disease.
T h e h ig h ly c o m p le x in te rd e p e n d e n c y b e tw e e n re g io n a l p e rfu s io n a n d w a ll m o tio n th a t u s u a lly p re v a ils in th e n o rm a l m y o c a rd iu m m a y th e o re tic a lly b e d is ru p te d in C h a g a s 'd is e a s e b y s e v e ra l m e c h a n is m s . F o r in s ta n c e , it s e e m s p la u s ib le to s p e c u la te th a t c h ro n ic re g io n a l h y p o p e rfu s io n , a s d e m o n s tra te d in th e in v e s tig a tio n s
m en tio n ed ab o v e, m ig h t lead to lo calized , p o ten tially rev ersib le d y ssy n erg y . T h is h y p o th esis is co m p atib le w ith th e resu lts o f stu d ies sh o w in g im p ro v em en t o f left v en tricu lar fu n ctio n in ch ro n ic ch ag asic p atien ts, w h o receiv ed acu te o r ch ro n ic ad m in istratio n o f d ip y rid am o le (1 8 ,2 0 ) an d iso so rb id e d in itrate (1 7 ,2 6 ). It is p o ssib le th at su ch am elio ratio n o f th e v en tricu lar p erfo rm an ce sh o w n in ch ag asic p atien ts co u ld m erely reflect m o re fav o rab le p relo ad an d afterlo ad co n d itio n s d u rin g th e effect o f th ese v aso d ilato r. H o w ev er, th e o b serv atio n o f d isap p earan ce o f 2 0 I-th alliu m p erfu sio n d efects after ch ro n ic treatm en t o f ch ag asic p atien ts w ith d ip y rid am o le, su p p o rts th e co n cep t th at ab o lish in g reg io n al u n d erp erfu sio n m ay co n trib u te to th e rev ersal o f w all m o tio n ab n o rm alities d o cu m en ted after ad m in istratio n o f v aso d ilato r (3 9 ).
W e co n sid er th at th ese in v estig atio n s sh o u ld b e v alid ated b y sp ecific stu d ies aim in g at th e co n firm atio n o f th e ex isten ce o f ch ro n ically u n d erp erfu sed , h y p o co n tractile m y o card iu m in C h ag as' h eart d isease. T h is w o u ld b e sim ilar to th e h ib ern atin g m y o card iu m seen in ch ro n ic co ro n ary artery d isease, an d m ig h t h av e relev an t clin ical im p licatio n s fo r th e m an ag em en t o f ch ag asic p atien ts.
T h is h y p o th esis, co h eren t w ith th e ex p erim en tal o b serv atio n s th at u n d erlie th e v ascu lar p ath o g en etic th eo ry o f C h ag as' d isease (8 ,1 1 ,3 8 ), is also co m p atib le w ith th e resu lts o f p relim in ary stu d ies in an im al m o d els o f th e d isease (3 0 ), an d in h u m an s (3 9 ), sh o w in g p ro m isin g b en eficial effects o f th erap eu tic in terv en tio n s w ith v aso d ilato rs.
iso so rb id e. Q u an titativ e an g io g rap h y w as p erfo rm ed in p ro x im al an d d istal seg m en ts o f th e left an terio r d escen d in g artery .
A ll 2 5 p atien ts h ad n o rm al co ro n ary arteries o r n o n sig n ifican t lesio n s
«
5 0 % red u ctio n o f lu m in al d iam eter). N o ep iso d e o f fo cal o r d iffu se co ro n ary sp asm co u ld b e d etected in an y o f th e p atien ts, w h o also h ad n o isch em ic electro card io g rap h ic ch an g es fo llo w in g h y p erv en tilatio n . M in o r co m p arab le ch an g es w ere o b serv ed in b o th g ro u p s, fo r h eart rate an d b lo o d p ressu re, after h y p erv en tilatio n an d n itrate ad m in istratio n . T h e PaC 02 d ecreased to 2 1 .9 an d 1 9 .8 m m h g , fo llo w in g
h y p erv en tilatio n , resp ectiv ely fo r th e ch ag asic an d co n tro l g ro u p s. T h e ab so lu te v alu es fo r th e lu m in al d iam eters, in m m , are p resen ted in T ab le 3 . B aselin e d iam eters w ere sig n ifican tly larg er in th e ch ag asic g ro u p . In co n trast, d iam eter ch an g es ev o k ed b y h y p erv en tilatio n an d n itrate ad m in istratio n w ere sig n ifican tly m o re p ro n o u n ced in th e co n tro l g ro u p , fo r b o th th e p ro x im al an d th e d istal seg m en ts o f th e left an terio r d escen d in g artery .
T a b le 3
A b s o lu te lu m in a l d ia m e te r (m m ) o f p ro x im a l (P -L A D ) a n d d is ta l (D -L A D ) s e g m e n ts o f th e le ft a n te rio r d e s c e n d in g c o ro n a ry a rte ry in c h ro n ic c h a g a s ic c a rd io m y o p a th y (C C C ) p a tie n ts a n d in n o rm a l
c o n tro ls (N ).
B 2 .7 2 :t0 .6 1 A O :t0 .2 2 .5 6 :tO A 1 A 4 :t0 .3
H -5 m in 2 .6 5 :t0 .5 1 .3 4 :t0 .2
2A7:tOA
1 A 1 :t0 .3H -1 0 m in 2 .6 1 :t0 .5 1 A O :t0 .2 2 A 2 :t0 .3 * 1 .2 5 :t0 .2 *
H -1 5 m in 2 .6 9 :t0 .6 1 .3 4 :t0 .1 2 .5 3 :tO A 1 .2 9 :t0 .2
O N IS 2 .8 6 :t0 .6 1 A 7 :t0 .2 2 .9 8 :t0 .6 **1 .7 4 :tO A **
B
=
b a s e lin e ; H -5 , 1 0 m in , 1 5 m in=
a fte r 5 , 1 0 a n d 1 5 m in u te s o f h y p e rv e n tila tio n ; O N IS = a fte r a d m in is tra tio no f 5 m g o f d in itra te is o s o rb id e b y s u b lin g u a l ro u te . * p <
0 .0 5 - ** P < 0 .0 1 , re la tiv e to th e re s p e c tiv e b a s e lin e
v a lu e s .
T h u s, co ro n ary sp asm d o es n o t seem to p lay a sig n ifican t ro le in th e g en esis o f an g in a-lik e sy m p to m s in C h ag as' h eart p atien ts. F u rth erm o re, v aso m o to r resp o n ses o f th e ep icard ial co ro n ary arteries to v aso co n stricto r an d v aso d ilato r stim u li are b lu n ted in ch ro n ic ch ag asic p atien ts.
3 -
Studies of coronary reactivity
tophysiological
and
pharmacological
stimuli in chronic chagasic patients.
V aso sp asm h as b een im p lied as th e m ech an ism u n d erly in g acu te isch em ic sy n d ro m es in C h ag as' h eart p atien ts (4 6 ). S in ce p ro lo n g ed h y p erv en tilatio n h as b een d em o n strated to in d u ce co ro n ary sp asm (th at is rev ersib le w ith n itrates) in p atien ts w ith P rin zm etal an g in a (3 ), w e co n d u cted a stu d y in ch ag asic p atien ts w ith an g in a-lik e sy m p to m s sev ere en o u g h to w arran t co ro n ary an g io g rap h y , to test d irectly th e h y p o th esis th at su ch p atien ts are p ro n e to h av e co ro n ary v aso sp asm resp o n sib le fo r th eir sy m p to m s (4 0 ). V aso m o to r resp o n ses to h y p erv en tilatio n an d su b lin g u al iso so rb id e d in itrate ad m in istratio n w ere stu d ied in th e ep icard ial co ro n ary arteries o f 1 4 ch ag asic p atien ts (m ean ag e
=
5 7 1 : ]] y ears) e ] I co n tro l su b jects also p resen tin g w ith an g in a (m ean ag e=
4 5 1 : ]5 y ears). A ll p atien ts w ere stu d ied at b aselin e an d 5 , 1 0 , an d ] 5 m in u tes after h y p erv en tilatio n fo r 5 m in u tes, an d ag ain fo llo w in g th e su b lin g u al ad m in istratio n o f 5 m g o f d in itrateeee
P-L A O O -L A O
N
P-L A O O -L A O
The findings
of this investigation,
showing relative
baseline vasodilation
in the coronary epicardial circulation,
seem to represent the counterpart,
in vivo, of the increased
volumetric
coronary
capacity
demonstrated
in necropsy
studies of chronic chagasic patients (11). The mechanisms
responsible
for these findings are not clear. The autonomic
dysfunction,
postulated
following
the necropsy
studies,
remains
a possible
explanation,
requiring
a direct
investigation.
Only one study addressing
the issues of
perfusion defects and autonomic
dysfunction,
in the same
group
of chagasic
patients,
has
been
reported,
no
correlation
between
both types of abnormalities
being
found (23). However,
it must be pointed out that, in this
study, only the autonomic
control of the sinus node was
directly assessed, and no attempt to test the regulation
of
the coronary circulation
was carried out.
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&
A N D R A D E , S .G . - A patogenia da m iocardite cronica chagasica (a im portancia das les6es isquem icas). A rq B ras M ed 45: 279-290, 1955.3. A R D IS S IN O , D .;.D E S E R V I, S .; F A L C O N E , e. et al. - R ole of hypocapnic alkalosis in hyperventilation-induced coronary artery spasm in variant angina. A m J C ardiol 59: 708-710,
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T A N O W IT Z , H . - A bnorm alities of the coronary m icrocirculation in acute m urine C hagas' disease. A m J T rop M ed H yg 34: 246-253,1985. .
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K O R O S T O F F , S . - C hagas' disease m asquerading as coronary artery disease. A rch Intern M ed 143: 144-145, 1983.10. F E R R E IR A , C .S .; L O P E S , E .R .; C H A P A D E IR O , E .; A L M E ID A , H .O . & S O U Z A , W .F . - C oronariografia e ventriculografia post m ortem na cardite chagasica cronica. C orrela< ;ao anatom o-radioI6gica. In: D ecourt, L .Y .
&
C am pos, O .M . M odernos C onhecim entos sobre D oem ;a de C hagas. B elo H orizonte, U niversidade F ederal de M inas G erais; A cadem ia M ineira de M edicina, 1981. p. 29-38.
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