This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.This study aims to identify adenovirus as a possible association with atrial fibrillation, as part of a larger investigation into a possible role as a cardiovascular pathogen. In vitro studies have established that adenovirus (Ad) can infect human vascular and myocardial cells. Adenovirus can be isolated in myocardial biopsies from patients with non-ischemic cardiomypathy. More recent studies have identified that adenovirus alters the expression of connexins in gap junctions, which comprise the cell-to-cell communication or electrical coupling of myocytes. Almost no infectious organisms have been studied as possible multifactorial agents in atrial fibrillation or atrial myocarditis. Connexins are a group of at least 20 highly conserved proteins; they allow for cellular communication through passage of ions, nutrients, second messengers, and small metabolites, as well as facilitating electrical coupling from one cell to neighboring cells. Disruption of these critical channels may lead to chaotic electrical activity (uncoupling) in the atria or ventricles of the heart. Adenovirus is a double-stranded DNA virus that causes respiratory, enteric, and conjunctival disease in humans. The virus is responsible for acute respiratory disease that has affected military recruits; for this reason an oral vaccine against certain serotypes was manufactured by the military and used extensively in the 1970's. Adenovirus is as common as the enteroviruses in cases of viral myocarditis leading to cardiomyopathy, predominantly adenovirus serotype 2. Atrial fibrillation is characterized electrocardiographically by the presence of rapid, irregular, fibrillatory waves that vary in size, shape, and timing. It is a disease with substantial morbidity; non-valvular atrial fibrillation confers a three to five-fold elevated risk of stroke. Focal areas of atrial myocarditis have been identified in patients with lone atrial fibrillation. Genetic mutations have been identified in some cases of lone and familial atrial fibrillation; viral insult could operate in addition to or independently of these genetic mutations. This study hypothesizes that adenoviral infection of myocytes or cardiac tissue leads to alterations in cell-to-cell communication, thereby disrupting normal atrial myocardial function leading to atrial fibrillation. The objective of the study is to identify the presence or absence of adenoviral DNA in bodily fluids in patients with lone atrial fibrillation. Serum and urine samples from patients with atrial fibrillation and controls will be tested by PCR for evidence of viral infection. PCR results will be reported as positive or negative and an odds ratio will be calculated.
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