EXPERIMENTAL VIRAL VALVULITIS 
N. P. DePasquale and George E. Burch* 
Non-congenital valvular disease is usually attributed 
to rheumatic fever even in the absence of a history of 
rheumatic carditis. The willingness of physicians to ac- 
cept occult or subclinical rheumatic fever as the cause 
of valvular disease in those patients who do not have a 
history of rheumatic fever has frustrated the search for 
etiologic factors other than rheumatic fever in acute 
and chronic valvular disease. Experimental studies in 
mice and cynomolgus monkeys have demonstrated that 
group Bi coxsackievirus infection may be associated 
with valvulitis and mural endocarditis in addition to 
pericarditis and myocarditis. Coxsackievirus Bi antigen 
was identified in damaged valve tissue by immuno- 
fluorescent technics. In some animals gross and micro- 
scopic lesions, which were strikingly similar to those of 
chronic valvular disease in man, were observed. There 
is a need to study the role of viruses in the pathogenesis 
of acute and chronic valvular disease in man. 
INTRODUCTION 
Viral disease has rarely been implicated as a 
cause of mural endocarditis or acute and 
chronic valvulitis, but clinicians and patholo- 
gists have long recognized that a variety of 
viral agents produce pericarditis and/or my- 
ocarditis. There is no knov^n mechanism to ex- 
plain why the pericardium and myocardium 
should be susceptible to viral diseases v^^hile the 
mural endocardium and valves are immune to 
viral attack. Physicians have readily accepted 
the diagnosis of rheumatic valvulitis even in the 
j absence of a history of rheumatic fever, and this 
I has possibly frustrated the search for etiologic 
alternatives. 
During the course of experiments designed to 
produce acute and chronic viral myocarditis in 
animals it v^^as found that coxsackievirus group 
B4 infection in addition to producing pericardi- 
tis and myocarditis was often associated with 
mural endocarditis and valvulitis. The pur- 
! pose of this paper is to review the results of 
I ♦ Tulane University, School of Medicine, Department of Medicine. 
these experiments and to discuss some of their 
implications in human disease. 
MATERIAL AND METHODS 
Two groups of experiments, which have been 
previously reported, were carried out.^'^ 
Group I: A random breed strain of more than 
200 HaM/ICR mice were inoculated intraperi- 
toneally with 0.1 ml of fluid containing eith- 
er 10^ 50% tissue culture infective dose 
(TCID50) or lO^TCIDso of group B4 coxsackie- 
virus. The viral stock was originally re- 
covered by Kibrick and Benirschke from a 
lO-day-old infant who died of encephalohe- 
patomyocarditis.^ The virus was obtained 
as monkey kidney culture passage strain. 
Control fluid from monkey kidney cul- 
ture was also obtained. Virus and control fluid 
were stored at — 65°C. The animals were killed 
2 to 60 days following inoculation. 
Group II: Seven cynomolgus monkeys were 
inoculated intravenously with 0.3 ml TCID50 of 
the same strain of virus as in the Group I exper- 
iments. Two monkeys were inoculated with 0.3 
ml of virus-free kidney culture fluid. The exper- 
imental animals were killed 51 to 200 days after 
inoculation and the control animals were killed 
51 to 231 days after inoculation. 
RESULTS 
Group I: Valvular endocarditis was found in 
55% and mural endocarditis in 50% of the 
mice inoculated with group B4 coxsackievirus. 
The tricuspid valve was involved in 43%, the mi- 
tral valve in 23%, the aortic valve in 10%, and 
the pulmonic valve in 5% of animals. Mural en- 
carditis involved the right ventricle in 20%, the 
right atrium in 18%, the left ventricle in 13%, 
and the left atrium in 10 % of animals. 
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