Viral infections of the heart are important causes of morbidity and mortality in children, but the exact mechanism(s) of myocardial damage are not fully understood. Acute myocarditis typically presents with severe clinical manifestations and, unfortunately, in many cases cardiac dysfunction is progressive. It has been hypothesized that idiopathic dilated cardiomyopathy (IDCM) may occur as a late sequela of acute or chronic viral myocarditis, either due to persistence of virus or due to an ongoing autoimmune process occurring secondary to previous exposure to the inciting virus. In addition to these conditions, viral infection of the heart is known to occur in the immunosuppressed post-operative cardiac transplant patient, and is unable to be differentiated histologically from acute graft rejection. Definitive diagnosis of viral myocarditis is often difficult, and available methods lack sensitivity and specificity. Previous work by others suggests that cytokines and/or cell adhesion molecules (CAMs) may play an important role in the pathogenesis of cardiac inflammatory conditions. We hypothesize that specific patterns of cytokine and/or CAM expression may occur in the setting of active viral myocarditis, IDCM, and virus-associated allograft rejection. The following specific aims are therefore proposed: 1) To investigate the frequency of occurrence and type of viral nucleic acid in cardiac tissue obtained from patients with the above conditions using the polymerase chain reaction (PCR); 2) To investigate the expression of intercellular adhesion molecule-1 (ICAM-1) and relevant cytokines such as interleukin-1 (IL-1) and tumor necrosis factor (TNF) by reverse transcriptase-PCR (RT-PCR) and correlate the results with routine histologic findings and presence or absence of viral genome; and 3) To develop reproducible methods of PCR amplification of ICAM-1 and relevant cytokines, in conjunction with amplification of viral nucleic acid, as a means of providing a rapid and more sensitive test to aid in the diagnosis of viral myocarditis or virus-associated cardiac allograft rejection. Further understanding of the role of CAMs and cytokines in these disease processes should lead to the development and clinical use of therapeutic agents directed against these molecules, thereby providing a means of altering the progression of inflammatory injury and reducing morbidity and mortality.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08HL003254-04
Application #
2466668
Study Section
Research Training Review Committee (RTR)
Project Start
1995-08-01
Project End
2000-06-30
Budget Start
1997-07-01
Budget End
1998-06-30
Support Year
4
Fiscal Year
1997
Total Cost
Indirect Cost
Name
University of Florida
Department
Pediatrics
Type
Schools of Medicine
DUNS #
073130411
City
Gainesville
State
FL
Country
United States
Zip Code
32611