Novel model of constrictive pericarditis associated with autoimmune heart disease in interferon-γ-knockout mice

Marina Afanasyeva, Dimitrios Georgakopoulos, De Lisa Fairweather, Patrizio Caturegli, David A. Kass, Noel R. Rose

Research output: Contribution to journalArticlepeer-review

Abstract

Background - Constrictive pericarditis represents a serious hemodynamic syndrome that may lead to heart failure. Studies of its pathophysiological mechanisms have been impeded by the lack of an animal model. Methods and Results - Cardiac myosin-induced experimental autoimmune myocarditis in Interferon (IFN)-γ-knockout (KO) mice results in increased cardiac inflammation and development of severe grossly detectable pericarditis. Using in vivo pressure-volume studies, we found that the acute phase of experimental autoimmune myocarditis in IFN-γ-KO mice was characterized by reduced left ventricular (LV) volumes compared with wild-type mice. The KO mice exhibited a classic restrictive/constrictive phenotype with decreased cardiac output, increased chamber stiffness, preserved ejection fraction, and impaired diastolic filling, characterized by reduced deceleration time and pressure tracings showing the square root sign similar to that observed in clinical cases of constrictive pericarditis. This phenotype was not associated with the severity of myocarditis but correlated with the presence of grossly detectable adhesive pericarditis present only in the KO group and characterized by increased pericardial inflammation and fibrosis. Comparison of IFN-γ-KO and wild-type mice matched for the severity of myocardial disease further confirmed that pericarditis, and not myocarditis, was responsible for smaller LV volumes, reduced cardiac output, increased cardiac stiffness, and increased peak filling rate adjusted for end-diastolic volumes in KO mice. Conclusions - Autoimmune heart disease in IFN-γ-KO mice results in increased pericardial inflammation and fibrosis, leading to constrictive phenotype during the acute phase of disease. It represents a novel animal model of constrictive pericarditis.

Original languageEnglish (US)
Pages (from-to)2910-2917
Number of pages8
JournalCirculation
Volume110
Issue number18
DOIs
StatePublished - Nov 2 2004

Keywords

  • Cardiac output
  • Hemodynamics
  • Inflammation
  • Myocarditis
  • Pressure-volume relation

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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