Weekly Doxorubicin Increases Coronary Arteriolar Wall and Adventitial Thickness

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dc.contributor.authorEckman, Delrae M.en
dc.contributor.authorStacey, R. Brandonen
dc.contributor.authorRowe, Roberten
dc.contributor.authorD'Agostino, Ralph, Jr.en
dc.contributor.authorKock, Nancy D.en
dc.contributor.authorSane, David C.en
dc.contributor.authorTorti, Frank M.en
dc.contributor.authorYeboah, Josephen
dc.contributor.authorWorkman, Susanen
dc.contributor.authorLane, Kimberly S.en
dc.contributor.authorHundley, W. Gregoryen
dc.date.accessioned2018-10-23T17:18:39Zen
dc.date.available2018-10-23T17:18:39Zen
dc.date.issued2013-02-21en
dc.description.abstractBackground Doxorubicin (DOX) is associated with premature cardiovascular events including myocardial infarction. This study was performed to determine if the weekly administration of DOX influenced coronary arteriolar medial and/or adventitial wall thickening. Methods Thirty-two male Sprague-Dawley rats aged 25.1± 2.4 weeks were randomly divided into three groups and received weekly intraperitoneal injections of normal saline (saline, n = 7), or low (1.5 mg/kg to 1.75 mg/kg, n = 14) or high (2.5 mg/kg, n = 11) doses of DOX. The animals were treated for 2–12 weeks, and euthanized at pre-specified intervals (2, 4, 7, or 10+ weeks) to obtain histopathologic assessments of coronary arteriolar lumen diameter, medial wall thickness, adventitial wall thickness, and total wall thickness (medial thickness + adventitial thickness). Results Lumen diameter was similar across all groups (saline: 315±34 µm, low DOX: 286±24 µm, high DOX: 242±27 µm; p = 0.22). In comparison to animals receiving weekly saline, animals receiving weekly injections of 2.5 mg/kg of DOX experienced an increase in medial (23±2µm vs. 13±3µm; p = 0.005), and total wall thickness (51±4µm vs. 36±5µm; p = 0.022), respectively. These increases, as well as adventitial thickening became more prominent after normalizing for lumen diameter (p<0.05 to p<0.001) and after adjusting for age, weight, and total cumulative DOX dose (p = 0.02 to p = 0.01). Animals receiving low dose DOX trended toward increases in adventitial and total wall thickness after normalization to lumen diameter and accounting for age, weight, and total cumulative DOX dose (p = 0.06 and 0.09, respectively). Conclusion In conclusion, these data demonstrate that weekly treatment of rats with higher doses of DOX increases coronary arteriolar medial, adventitial, and total wall thickness. Future studies are warranted to determine if DOX related coronary arteriolar effects are reversible or preventable, exacerbate the known cardiomyopathic effects of DOX, influence altered resting or stress-induced myocardial perfusion, or contribute to the occurrence of myocardial infarction.en
dc.description.versionPublished versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1371/journal.pone.0057554en
dc.identifier.eissn1932-6203en
dc.identifier.issue2en
dc.identifier.othere57554en
dc.identifier.pmid23437398en
dc.identifier.urihttp://hdl.handle.net/10919/85462en
dc.identifier.volume8en
dc.language.isoenen
dc.publisherPLOSen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttps://creativecommons.org/licenses/by/4.0en
dc.titleWeekly Doxorubicin Increases Coronary Arteriolar Wall and Adventitial Thicknessen
dc.title.serialPLOS ONEen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten

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