C O M U N IC A Ç Ã O
A B S E N C E O F H Y P E R S E N S IT IV IT Y T O T H E N E G A T IV E C H R O N O T R O P IC E F F E C T O F A C E T Y L C H O L IN E IN
T H E A T R IA O F M IC E A C U T E L Y IN F E C T E D W IT H
T R Y P A N O S O M A C R U Z I , C L S T R A IN .
R e v i s t a d a S o c i e d a d e B r a s i l e i r a d e M e d ic i n a T r o p i c a l
2 4 ( 4 ) : 2 5 9 - 2 6 1 , o u t - d e z , 1 9 9 1
J o sé G u ilh erm e P . P ires a n d F a u sto E . L im a P ereira
Cardiac parasym pathetic denervation during the acute phase o f T r y p a n o s o m a c r u z i infection is b eliev e d to p lay an im p o rtan t ro le in the p a th o g e n e s is o f C h a g a s 'c a rd io p a th y 5. As
T r y p a n o s o m a c r u z i infection in mice produces m y o ca rd itis w ith ch a rac te ristic s sim ilar to Chagas 'm yocarditis in hum ans25, this model was chosen to investigate the sensitivity o f atrial m uscarinic receptors to exogenously administered acetylcholine (ACh). In a previous study10 using atria o f m ice chronically infected w ith either a reticulotropic (Y) o r a m yotropic (CL) strain of T r y p a n o s o m a c r u z i, it was reported no significant change in the sensitivity to ACh, a result that m ight be due to reinnervation processes occuring after the acute phase, as shown in rats78. So, itw as decided to investigate the atrial reactivity to ACh during the acute phase o f T r y p a n o s o m a c r u z i infection in mice. The CL strain was choses because it induces a m ore severe myocarditis than the Y strain 1.
Albino mice weighing 24-32 g were inoculated intraperitonally w ith 200 trypam astigotes/g o f a CL strain o f T r y p a n o s o m a c r u z i .
All infected animals exhibited blood parasites after infectio n, as determ ined by m eans o f m icroscopic exam ination o f a drop o f blood 14 days after infection. A fter 30 days o f infection
(acute phase) the anim als w ere killed for in v i t r o
recording o f the effects o f ACh. Age-matched
Departments ofPhysiological Sciences and Pathology, Biomedical Center, Espirito Santo Federal University, Vitória, ES, Brazil. Research partially supported by Fundação Ceciliano Abel de Almeida.
Address f o r correspondence: Prof. José Guilherme Pinheiro Pires, Dept” de Ciências Fisiológicas/CB/UFES. Caixa Postal 780, 29001 Vitória, ES, Brasil.
Recebido para publicação em 20/06/91.
noninfected mice w ere used as controls. A tria (left and right) w ere mounted in a 7 m l-organ bath (32°C), filled w ith m odified Locke solution (154 mM N aCl, 5.6 mM KC1, 2 .2 m M CaCl2, 0.08 mM NaH2P 0 4, 1.9 mM N a H C 0 3 and 5 .5 mM glucose) and bubbled w ith 02. The atria w ere attached to a force transducer (Narco F-50) and tension was recorded on a N arco DPM -4B polygraph. An initial tension o f 0.1 g was applied to the tissues. An equilibration period o f 40 m in was allow ed before experim ents w ere started. A cetylcholine chloride (from Sigma C o.) was added to the organ bath and a dose-response curve produced. T he effect or ACh was expressed as the decrease in beating rate relative to the previous basal value (bpm). D ata were expressed as m ean ± S .E .M . and analyzed statistically by the S tu d e n t's i-test, P less than 0.05 being considered significant. A fter the experim ents, the atria w ere fixed in 10% form alin and were paraffin embedded for ligh t m icroscopy.
H istological exam ination o f the atria from infected mice showed m ultifocal m yocarditis with destruction o f some cardiac cells and presence of m ononuclear exudate. The atrial ganglia observed in each case showed focal inflam m atory lesions, w ith apparent low level o f neuronal destruction. Basal atrial rate was sim ilar in both groups: 250 + 1 1 bpm in chagasic (n = 6 ) and 253 ± 1 0 bpm in control (n = 6 ) mice. The dose-response curve to ACh in atria from infected mice did no t significantly differ from the control (Figure 1).
These results dem onstrate that acute infection o f mice w ith the C L strain o f T r y p a n o s o m a c r u z i d o e s not induce cholinergic supersensitivity, as it had already been dem onstrated during the chronic phase11. Chagas 'd isease is still considered to be a natural hum an m odel o f peripheral autonom ic denervation10, and lesions in cardiac ganglia have
C o m u n i c a ç ã o . P ir e s J G P , P e r e i r a F E L . A b s e n c e o f h y p e r s e n s i t i v i t y to th e n e g a t i v e c h r o n o t r o p i c e f e c t o f a c e t y l c h o l i n e in th e a tr i a o f m i c e a c u t e l y i n fe c t e d w ith T rypanosom a cruzi, C L s t r a i n . R e v i s t a d a S o c i e d a d e B r a s i l e i r a d e M e d i c i n a T r o p i c a l 2 4 : 2 5 9 - 2 6 1 , o u t- d e z , 1 9 9 1
been described in mice acutely infected with
T r y p a n o s o m a c r u z i2. However, the intensity of denervation in atrial ganglia has notbeen established in mice w ith acute T r y p a n o s o m a c r u z i infection. The lesions that w e observed in atrial ganglia were focal and do n ot suggest a severe depletion of nerve cells in those ganglia. Reduction o f cardiac neurons has been reported in rats during the acute phase o f T r y p a n o s o m a c r u z i infection1. However, quantitative studies o f rats chronically infected w ith T r y p a n o s o m a c r u z i showed no significant differences in the num ber of neurons in respect to
age- and sex-matched control rats49. Therefore, it is possible that the absence o f supersensitivity to ACh that w e observed in isolated atria o f acutely infected m ice w ould be due to the low intensity of denervation in atrial ganglia.
A CKNOW LEDGM ENTS
W e wish to thank D r. F. N egreiros Gomes and M r. Nilo Faria for their invaluable help during the preparation o f the m anuscript.
C o m u n ic a ç ã o . P ir e s J G P , P e r e ir a F E L . A b s e n c e o f h y p e r s e n s i tiv ity to th e n e g a tiv e c h r o n o t r o p ic e f e c t o f
a c e ty lc h o lin e in th e a tr ia o f m ic e a c u te ly in f e c te d w ith Trypanosoma cruzi, C L s tr a in . R e v is ta d a S o c ie d a d e B r a s i le i r a d e M e d ic in a T r o p ic a l 2 4 : 2 5 9 - 2 6 1 , o u t- d e z , 1 9 9 1
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