Published Online
on October 25, 2004

A more recent version of this article appeared on November 2, 2004

This Article Full Text (PDF) All Versions of this Article: 110/18/2910    most recent 01.CIR.0000147538.92263.3Av1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Afanasyeva, M. Articles by Rose, N. R. Search for Related Content PubMed PubMed Citation Articles by Afanasyeva, M. Articles by Rose, N. R. Pubmed/NCBI databases Substance via MeSH Medline Plus Health Information Autoimmune Diseases Cardiomyopathy Related Collections Pericardial disease Remodeling Animal models of human disease Genetically altered mice Growth factors/cytokines Heart failure - basic studies Myocardial cardiomyopathy disease

Submitted on June 9, 2004
Revised on August 5, 2004
Accepted on August 11, 2004

Novel Model of Constrictive Pericarditis Associated With Autoimmune Heart Disease in Interferon--Knockout Mice

Marina Afanasyeva MD, MPH, PhD^*, Dimitrios Georgakopoulos PhD, DeLisa Fairweather PhD, Patrizio Caturegli MD, David A. Kass MD, and Noel R. Rose MD, PhD

From the Department of Pathology (M.A., D.F., P.C., N.R.R.), Department of Medicine (D.G., D.A.K.), and W. Harry Feinstone Department of Molecular Microbiology and Immunology (N.R.R.), Johns Hopkins Medical Intitutions, Baltimore, Md.

^* To whom correspondence should be addressed. E-mail: afanasym{at}ucalgary.ca.

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)--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--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--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--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.

Key words: cardiac output • pressure-volume relation • hemodynamics • inflammation • myocarditis

This article has been cited by other articles:

				J. Morton, B. Coles, K. Wright, A. Gallimore, J. D. Morrow, E. S. Terry, P. B. Anning, B. P. Morgan, V. Dioszeghy, H. Kuhn, et al. Circulating neutrophils maintain physiological blood pressure by suppressing bacteria and IFN{gamma}-dependent iNOS expression in the vasculature of healthy mice Blood, May 15, 2008; 111(10): 5187 - 5194. [Abstract] [Full Text] [PDF]

				D. Cihakova, J. G. Barin, M. Afanasyeva, M. Kimura, D. Fairweather, M. Berg, M. V. Talor, G. C. Baldeviano, S. Frisancho, K. Gabrielson, et al. Interleukin-13 Protects Against Experimental Autoimmune Myocarditis by Regulating Macrophage Differentiation Am. J. Pathol., May 1, 2008; 172(5): 1195 - 1208. [Abstract] [Full Text] [PDF]

				D. Fairweather, S. Frisancho-Kiss, D. B. Njoku, J. F. Nyland, Z. Kaya, S. A. Yusung, S. E. Davis, J. A. Frisancho, M. A. Barrett, and N. R. Rose Complement Receptor 1 and 2 Deficiency Increases Coxsackievirus B3-Induced Myocarditis, Dilated Cardiomyopathy, and Heart Failure by Increasing Macrophages, IL-1beta, and Immune Complex Deposition in the Heart J. Immunol., March 15, 2006; 176(6): 3516 - 3524. [Abstract] [Full Text] [PDF]