Browsing by Author "Larsen, Timothy R."

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    Intercalated Disk Extracellular Nanodomain Expansion in Patients With Atrial Fibrillation
    Raisch, Tristan B.; Yanoff, Matthew S.; Larsen, Timothy R.; Farooqui, Mohammed A.; King, D. Ryan; Veeraraghavan, Rengasayee; Gourdie, Robert G.; Baker, Joseph W.; Arnold, William S.; AlMahameed, Soufian T.; Poelzing, Steven (Frontiers, 2018-05-04)
    Aims: Atrial fibrillation (AF) is the most common sustained arrhythmia. Previous evidence in animal models suggests that the gap junction (GJ) adjacent nanodomain - perinexus - is a site capable of independent intercellular communication via ephaptic transmission. Perinexal expansion is associated with slowed conduction and increased ventricular arrhythmias in animal models, but has not been studied in human tissue. The purpose of this study was to characterize the perinexus in humans and determine if perinexal expansion associates with AF. Methods: Atrial appendages from 39 patients (pts) undergoing cardiac surgery were fixed for immunofluorescence and transmission electron microscopy (TEM). Intercalated disk distribution of the cardiac sodium channel Nav1.5, its beta 1 subunit, and connexin43 (C x 43) was determined by confocal immunofluorescence. Perinexal width (Wp) from TEM was manually segmented by two blinded observers using ImageJ software. Results: Nav1.5, beta 1, and C x 43 are co-adjacent within intercalated disks of human atria, consistent with perinexal protein distributions in ventricular tissue of other species. TEM revealed that the GJ adjacent intermembrane separation in an individual perinexus does not change at distances greater than 30 nm from the GJ edge. Importantly, Wp is significantly wider in patients with a history of AF than in patients with no history of AF by approximately 3 nm, and Wp correlates with age (R = 0.7, p < 0.05). Conclusion: Human atrial myocytes have voltage-gated sodium channels in a dynamic intercellular cleft adjacent to GJs that is consistent with previous descriptions of the perinexus. Further, perinexal width is greater in patients with AF undergoing cardiac surgery than in those without.
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    Systemic Embolization from an Unusual Intracardiac Mass in the Left Ventricular Outflow Tract
    Okoro, Kelechukwu U.; Larsen, Timothy R.; Lystash, John C. (Hindawi, 2017-06-07)
    Endocarditis can affect any endocardial surface; in the vast majority of cases, the cardiac valves are involved. It is exceedingly rare to develop infective endocarditis on the endocardium of the left ventricular outflow tract due to the high velocity of blood that traverses this area. Herein, we present a rare case of left ventricular outflow tract endocarditis that likely occurred secondary to damage to the aortic valve leaflets (from healed prior aortic valve endocarditis) causing a high velocity aortic valve regurgitant jet that impinged upon the interventricular septum which damaged the endocardium and resulted in a fibrotic “jet lesion.” This fibrous jet lesion served as a nidus for bacterial proliferation and vegetation formation. The high shear stress (due to high blood flow velocity through the left ventricular outflow tract) likely promoted the multiple embolic events observed in this case. Our patient was successfully treated with aortic valve replacement, vegetation resection, and antibiotics.