An animal model of chronic rheumatic valvulitis induced by formalin-killed streptococci

Rheumatol Int. 2010 Nov;30(12):1621-5. doi: 10.1007/s00296-009-1246-3. Epub 2009 Dec 12.

Abstract

Rheumatic heart disease is the most severe complication of rheumatic fever. Till date, very few successful animal models of rheumatic valvular disease have been reported. This study aimed at developing a suitable animal model of chronic rheumatic valvulitis for further investigation and prevention of rheumatic heart disease. Lewis rats were immunized with one administration of formalin-killed and sonicated group A streptococci together with Complete Freund's Adjuvant every 7 days for three cycles followed by group A streptococci alone till killing. Control rats were administered adjuvants and saline. Rats in group 1 were killed 12 weeks after the initial injection. Rats in group 2 and control group were killed 24 weeks after the initial injection. Results 62.5% (5/8) of rats in group 1 developed myocarditis and 50% (4/8) developed valvulitis. Histological examination of cardiac sections showed only cellular infiltrates. In contrast, 75% (6/8) of rats in group 2 developed rheumatic-like myocarditis and 62.5% (5/8) developed chronic valvulitis. Histological manifestations of the hearts in group 2 animals involved not only acute damage such as cellular infiltrates, Aschoff-like cells, verrucous vegetation, but also chronic lesions such as fibrosis, vascular neogenesis. None of the rats (0/8) in control group presented myocarditis or valvulitis. Lewis rat repeatedly immunized with formalin-killed GAS may be a suitable animal model of chronic rheumatic valvulitis. It may be useful for future investigation of the pathogenesis and possible preventive strategies of human rheumatic heart disease.

MeSH terms

  • Animals
  • Antigens, Bacterial / immunology*
  • Disease Models, Animal
  • Female
  • Formaldehyde / pharmacology
  • Heart / microbiology
  • Heart Valve Diseases / immunology*
  • Heart Valve Diseases / microbiology
  • Heart Valve Diseases / pathology
  • Myocarditis / immunology*
  • Myocarditis / pathology
  • Myocardium / immunology
  • Myocardium / pathology
  • Rats
  • Rats, Inbred Lew
  • Rheumatic Heart Disease / immunology*
  • Rheumatic Heart Disease / microbiology
  • Rheumatic Heart Disease / pathology
  • Rheumatic Nodule / immunology
  • Rheumatic Nodule / microbiology
  • Rheumatic Nodule / pathology
  • Streptococcal Infections / complications
  • Streptococcal Infections / immunology
  • Streptococcus pyogenes / drug effects
  • Streptococcus pyogenes / immunology*
  • Streptococcus pyogenes / pathogenicity

Substances

  • Antigens, Bacterial
  • Formaldehyde