{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T06:40:54Z","timestamp":1790318454855,"version":"4.1.0"},"reference-count":45,"publisher":"American Physiological Society","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"published-print":{"date-parts":[[2012,1]]},"abstract":"<jats:p> Cardiac conduction through gap junctions is an important determinant of arrhythmia susceptibility. Yet, the relationship between degrees of G<jats:sub>j<\/jats:sub> uncoupling and conduction velocity (\u03b8) remains controversial. Conflicting results in similar experiments are normally attributed to experimental differences. We hypothesized that interstitial volume modulates conduction velocity and its dependence on G<jats:sub>j<\/jats:sub>. Interstitial volume (V<jats:sub>IS<\/jats:sub>) was quantified histologically from guinea pig right ventricle. Optical mapping was used to quantify conduction velocity and anisotropy (AR<jats:sub>\u03b8<\/jats:sub>). Albumin (4 g\/l) decreased histologically assessed V<jats:sub>IS<\/jats:sub>, increased transverse \u03b8 by 71 \u00b1 10%, and lowered AR<jats:sub>\u03b8<\/jats:sub>. Furthermore, albumin did not change isolated cell size. Conversely, mannitol increased V<jats:sub>IS<\/jats:sub>, decreased transverse \u03b8 by 24 \u00b1 4%, and increased AR<jats:sub>\u03b8<\/jats:sub>. Mannitol also decreased cell width by 12%. Furthermore, mannitol was associated with spontaneous ventricular tachycardias in three of eight animals relative to zero of 15 during control. The \u03b8-G<jats:sub>j<\/jats:sub> relationship was assessed using the G<jats:sub>j<\/jats:sub> uncoupler carbenoxolone (CBX). Whereas 13 \u03bcM CBX did not significantly affect \u03b8 during control, it slowed transverse \u03b8 by 38 \u00b1 9% during mannitol (edema). These data suggest changes in V<jats:sub>IS<\/jats:sub> modulate \u03b8, AR<jats:sub>\u03b8<\/jats:sub>, and the \u03b8-G<jats:sub>j<\/jats:sub> relationship and thereby alter arrhythmia susceptibility. Therefore, V<jats:sub>IS<\/jats:sub> may underlie arrhythmia susceptibility, particularly in diseases associated with gap junction remodeling. <\/jats:p>","DOI":"10.1152\/ajpheart.00868.2011","type":"journal-article","created":{"date-parts":[[2011,10,22]],"date-time":"2011-10-22T02:58:46Z","timestamp":1319252326000},"page":"H278-H286","source":"Crossref","is-referenced-by-count":88,"title":["Interstitial volume modulates the conduction velocity-gap junction relationship"],"prefix":"10.1152","volume":"302","author":[{"given":"Rengasayee","family":"Veeraraghavan","sequence":"first","affiliation":[{"name":"Nora Eccles Harrison Cardiovascular Research and Training Institute,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed E.","family":"Salama","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Utah, Salt Lake City, 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