Fwd: [ARVD-FORUM] Naxos' disease in dogs? Dr. Perez Riera
ARVD Symposium
info at arvd-symposium.org
Tue Apr 5 16:21:23 ART 2005
English - Spanish
Dear Dr Carlos H. Lightowler due to scant existing animal models, the etiology
and pathogenesis of ARVC/D remain unknown or incompletely solved (the
pathophysiological mechanisms have been impaired by lack of suitable animal
models. To this date, three animals have been used for this purpose:
1) COMMON DOMESTIC CAT: Fox et al have identified a ctinically relevant
cardiomyopathy. Such cardiomyopathy closely resembles human ARVC/D. The
relevance of this unique feline model of human disease will be important in
the definition of pathogenesis and in the research of mechanisms accountable
for the progression of the disease in ARVC/D. (Fox PR, Maron BJ, Basso C, Liu
SK, Thiene G. Spontaneously occurring arrhythmogenic right ventricular
cardiomyopathy in the domestic cat: A new animal model similar to the human
disease. Circulation. 2000; 102:1863-1870).
Recently Harvey et al. sowed two cat affected. On 24-hour (Holter)
electrocardiogram recording revealed complete atrioventricular block and
multiform ventricular ectopics in both cats, with the addition of ventricular
tachycardia, ventricular bigeminy and R-on-T phenomenon in one of them.
(Harvey AM, Battersby IA, Faena M, Fews D, Darke PG, Ferasin L.Arrhythmogenic
right ventricular cardiomyopathy in two cats. J Small Anim Pract. 2005;
46:151-156.). One cat had also experienced previous episodes of syncope. On
echocardiography, the right ventricle and atrium were massively dilated and
hypokinetic. The survival times of the cats were three days and 16 days
following diagnosis. Histopathology in one case revealed fibro-fatty
infiltration of the myocardium, predominantly affecting the right ventricular
free wall.
2) BOXER DOGS: this seems to be the ideal animal model to study the
human disease, since it reproduces spontaneously and transmits genetically
the same etiopathogenic, histopathological, anatomopathological and clinical
features as in humans. (Basso C, Fox PR, Meurs KM, Towbin JA, Spier AW,
Calabrese F, Maron BJ, Thiene G. Arrhythmogenic right ventricular
cardiomyopathy causing sudden cardiac death in boxer dogs: a new animal model
of human disease. Circulation. 2004; 109: 1180-1185.). This model could be
helpful to grasp the pathogenic mechanisms of ARVC/D;
3) GENETICALLY MODIFIED MICE. (Asano Y, Takashima S, Asakura M, et al.
Lamr1 functional retroposon causes right ventricular dysplasia in mice. Nat
Genet. 2004; 36:123-130.).
The possible causes and mechanism include:
(1) APOPTOSIS;
(2) INFLAMMATION;
(3) DYSPLASIA;
(4) TRANSDIFFERENTIATION (Fontaine G, Mallat Z, Fornes P, et al.
Etiopathogenesis of arrhythmogenic right ventricular dysplasia Ann Cardiol
Angeiol (Paris). 2000; 49:37-47.) (Wang QW, Liu L. Arrhythmogenic right
ventricular cardiomyopathy Fa Yi Xue Za Zhi. 2004; 20:35-36.), and
(5) TRANSCRIPTIONAL REGULATION (Asano Y, Takashima S, Asakura M, et al.
Lamr1 functional retroposon causes right ventricular dysplasia in mice. Nat
Genet. 2004; 36:123-130.).
Best Regard
Andrés Ricardo Pérez Riera
----------------------------------------------------------
Português
Prezado Dr Carlos H. Lightowler devido a escassez modelos animais existentes a
etiologia e patogênese da DAVD permanece desconhecida ou incompletamente
esclarecida. O mecanismo patofisiológicos não tem sido esclarecido pela
pouca divulgação do modelo animal. Até o presente momento três animais têm
sido empregados com este propósito:
1) GATO DOMÉSTICO: Foxe e col. identificaram neste animal
cardiomiopatia clínica relevante. Esta cardiomiopatia é muito semelhante e
lembra muito a DAVD humana. A relevância de este unico modelo felino da
doença huana será importante na definição da patogênese e na pesquiza de
mecanismos implicados na progressão da doença (Fox PR, Maron BJ, Basso C,
Liu SK, Thiene G. Spontaneously occurring arrhythmogenic right ventricular
cardiomyopathy in the domestic cat: A new animal model similar to the human
disease. Circulation. 2000; 102:1863-1870..)
Recentemente Harvey et al. apresentou 2 gatos afetados, No Holter de 24h e
ECG detectou bloqueio AV completo extrasistoles polimórficas em ambos os
gatose TV bigeminsimo ventricular e fenômeno R sobre T em um dos gatos
(Harvey AM, Battersby IA, Faena M, Fews D, Darke PG, Ferasin L.Arrhythmogenic
right ventricular cardiomyopathy in two cats. J Small Anim Pract. 2005;
46:151-156.). Um dos gato teve eposôdio de síncope. No Ecocardiograma o VD e
AD estavam massivamente dilatados, o VD estava hipocinético. A sobrevida dos
gatos foi de 3 dias e 16 após o diagnóstico. Histopatologicamente um caso
revelou Infiltração fibro-gordurosa predominantemente no VD na sua parede
livre.
2) CÃES BOXERS: Este parece ser o modelo animal ideal para o estudo da
enfermidade humana uma vez que se transmite geneticamente, possui a mesma
etiopatogenia histopatologia, anatomopatologia e clínica dos humanos (Basso
C, Fox PR, Meurs KM, Towbin JA, Spier AW, Calabrese F, Maron BJ, Thiene G.
Arrhythmogenic right ventricular cardiomyopathy causing sudden cardiac death
in boxer dogs: a new animal model of human disease. Circulation. 2004; 109:
1180-1185.). Este modelo poderá ahudar a entender a patogenia da DAVD.
3) RATOS GENETICAMENTE MODIFICADOS (Asano Y, Takashima S, Asakura M,
Shintani Y, Liao Y, Minamino T, Asanuma H, Sanada S, Kim J, Ogai A, Fukushima
T, Oikawa Y, Okazaki Y, Kaneda Y, Sato M, Miyazaki J, Kitamura S, Tomoike H,
Kitakaze M, Hori M. Lamr1 functional retroposon causes right ventricular
dysplasia in mice. Nat Genet. 2004; 36:123-130.).
As possíveis causas e mecanismos incluem:
1) APOPTOSE;
2) INFLAMAÇÃO;
3) DISPLASIA;
4) TRANSDIFERENCIAÇÃO.
5) REGULAÇÃO TRANSCRIPCIONAL.
Saudações
Andrés Ricardo Pérez Riera.
---------- Mensaje reenviado ----------
English - Spanish
Dear friends,
Let me send this comment to the Forum, which I think may be interesting. I
am a veterinarian and Professor of Veterinarian Cardiology at the Faculty of
Veterinary Sciences of the Universidad de Buenos Aires.
In a breed of our canine patients, the Boxer, there is a disease called
arrhythmogenic right ventricular cardiomyopathy, which presents outstanding
similarities to the humane ARVD. Its presents most frequently at around two
years old (equivalent to about 20 years old in a man).
The process sometimes evolves without symptoms, except for the presence of
right ventricular extrasystoles or the consultation is made because of the
development of "syncopes", most of the times associated to long ventricular
paroxysmal tachycardias (I attach a tracing, typical of the disease).
http://www.arvd-symposium.org/files/CVDA.jpg
Generally, asymptomatic patients, but with presence of right ventricular
extrasystoles, are studied with 24 hours Holter. If they present ventricular
extrasystoles more frequently than 20 per hour, they are treated with
beta-blockers (generally Atenolol), and if there is some run of paroxysmal
ventricular tachycardia, mexiletine is added. In general, early treatment
delays the appearance of ventricular dysfunction, which in all cases comes
to the end of the process (some four years, if the patient is on
medication). First, right ventricular dysfunction appears (% FA lower than
28% and Tei index of >0.40), and then it becomes global cardiac dysfunction
and death. Sudden deaths are not uncommon (generally, undiagnosed or
untreated patients).
There are not many references about the anatomopathologic aspects of the
disease, though the replacement of the work muscle with fiber tissue has
been mentioned. There is a clear hereditary predisposition. However, studies
about it are incomplete.
Another interesting data. In a series of 57 cases of the disease, all the
diseased people were associated to a certain type of hair: striped dark
brown (the breed has various types of hair: light brown, light brown with
white chest, light brown with white neck, and the mentioned striped dark
brown). Some possible resemblance to the Naxus illness?
I hope these comments are useful, at least as an anecdote. However, this
breed could be an excellent experimental natural model for the study of this
disease.
Best regards for all,
Carlos H. Lightowler DVM
--------------------------------------------------
Estimados amigos
Me permito enviar al foro este comentario porque creo que puede
ser de interés. Soy médico veterinario y Profesor de Cardiología Veterinaria
en la Facultad de Ciencias veterinarias de la Universidad de Buenos Aires.
En una raza de nuestros pacientes caninos, la Bóxer existe una enfermedad
denominada Cardiomiopatía ventricular derecha arritmogénica que presenta
llamativas similitudes con la AVRD del hombre. Su presentación más frecuente
es alrededor de los 2 años de edad (equivalente a unos 20 años del hombre).
El proceso cursa a veces asintomáticamente, salvo por la presencia de
extrasístoles ventriculares derechas o se realiza la consulta por el
desarrollo de "síncopes", la mayoría de las veces asociados a taquicardias
paroxísticas ventriculares prolongadas (adjunto un trazado, típico de la
enfermedad).
http://www.arvd-symposium.org/files/CVDA.jpg
Generalmente los pacientes asintomático pero con presencia de
extrasístoles ventriculares derechas son estudiados con Holter de 24 hs. Si
presentan extrasístoles ventriculares con mayor frecuencia de 20 por hora,
son tratados con betabloqueantes (generalmente Atenolol) y si existe alguna
corrida de taquicardia ventricular paroxística, se agrega mexiletina. En
general el tratamiento precoz, retrasa la aparición de la disfunción
ventricular, la cual en todos los casos llega hacia el final del proceso
(unos cuatro años si el paciente está medicado). Primero aparece disfunción
ventricular derecha (%AF menor de 28% e índice de Tei de >0,40), para luego
convertirse en disfunción cardiaca global y muerte. No son raras las muertes
súbitas (generalmente en los pacientes no diagnosticados o no tratados).
No existen demasiadas referencias respecto a los aspectos
anatomopatológicos de la enfermedad, si bien se ha mencionado en algunos
casos el reemplazo del músculo de trabajo por tejido fibroso. Existe una
clara predisposición hereditaria. Sin embargo los estudios al respecto son
incompletos.
Otro dato interesante. En una serie de 57 casos de la
enfermedad, todos los enfermos estaban asociados a un determinado pelaje:
marrón oscuro atigrado (la raza posee varios pelajes: marrón claro, marrón
claro con pecho blanco, marrón claro con cuello blanco y el mencionado
marrón oscuro atigrado). Alguna posible semejanza con la enfermedad de Naxos?
.
Espero que estos comentarios sirvan, aunque se como anécdota.
Sin embargo, esta raza puede ser un excelente modelo experimental natural
para el estudio de la enfermedad.
Afectuosos saludos para todos
Carlos H. Lightowler DVM
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