{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:19:25Z","timestamp":1760059165127,"version":"build-2065373602"},"reference-count":49,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2025,5,27]],"date-time":"2025-05-27T00:00:00Z","timestamp":1748304000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Foundation for Heart Science","award":["2214008"],"award-info":[{"award-number":["2214008"]}]},{"name":"Daniel M. Soref Charitable Trust at Medical College of Wisconsin","award":["2214008"],"award-info":[{"award-number":["2214008"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Radiation therapy (RT) plays a vital role in managing thoracic cancers, though it can lead to adverse effects, including significant cardiotoxicity. Understanding the risk factors like hypertension in RT is important for patient prognosis and management. A Dahl salt-sensitive (SS) female rat model was used to study hypertension effect on RT-induced cardiotoxicity. Rats were fed a high-salt diet to induce hypertension and then divided into RT and sham groups. The RT group received 24 Gy of whole-heart irradiation. Cardiac function was evaluated using MRI and blood pressure measurements at baseline, 8 weeks and 12 weeks post-RT. Histological examination was performed after the last timepoint or animal death. The hypertensive RT rats demonstrated significant decreases in left-ventricular ejection fraction (EF) (45 \u00b1 7.2%) compared to sham (68 \u00b1 7.3%). Furthermore, circumferential (Ecc) and radial (Err) myocardial strains were significantly reduced (Ecc: \u22127.4 \u00b1 2.0% RT rats vs. \u221211 \u00b1 2.4% sham; Err: 15 \u00b1 6.5% RT rats vs. 23 \u00b1 8.9% sham). Histological analysis revealed significant pathophysiological remodeling post-RT, including nuclear size, interstitial fibrosis, necrosis, and the presence of inflammatory cells. This study provides valuable insights into the cardiotoxic effects of RT in the context of hypertension, highlighting the potential of using MRI for improved risk assessment with potential for future clinical translation.<\/jats:p>","DOI":"10.3390\/life15060862","type":"journal-article","created":{"date-parts":[[2025,5,29]],"date-time":"2025-05-29T06:25:04Z","timestamp":1748499904000},"page":"862","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Radiation-Induced Cardiotoxicity in Hypertensive Salt-Sensitive Rats: A Feasibility Study"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9367-6605","authenticated-orcid":false,"given":"Dayeong","family":"An","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering, Medical College of Wisconsin, Milwaukee, WI 53226, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alison","family":"Kriegel","sequence":"additional","affiliation":[{"name":"Deaprtment of Physiology, Medical College of Wisconsin, Milwaukee, WI 53226, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6479-0046","authenticated-orcid":false,"given":"Suresh","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Pathology & Laboratory Medicine, Medical College of Wisconsin, Milwaukee, WI 53226, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heather","family":"Himburg","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI 53226, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian","family":"Fish","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI 53226, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Slade","family":"Klawikowski","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI 53226, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Rowe","sequence":"additional","affiliation":[{"name":"Department of Mathematical and Statistical Sciences, Marquette University, Milwaukee, WI 53233, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marek","family":"Lenarczyk","sequence":"additional","affiliation":[{"name":"Department of Surgery, Medical College of Wisconsin, Milwaukee, WI 53226, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7899-3266","authenticated-orcid":false,"given":"John","family":"Baker","sequence":"additional","affiliation":[{"name":"Department of Surgery, Medical College of Wisconsin, Milwaukee, WI 53226, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4292-4669","authenticated-orcid":false,"given":"El-Sayed","family":"Ibrahim","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Medical College of Wisconsin, Milwaukee, WI 53226, USA"},{"name":"Department of Radiology, Medical College of Wisconsin, Milwaukee, WI 53226, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"193","DOI":"10.7150\/ijms.3635","article-title":"Cancer and radiation therapy: Current advances and future directions","volume":"9","author":"Baskar","year":"2012","journal-title":"Int. J. Med. Sci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1016\/j.ijrobp.2009.09.064","article-title":"Radiation-related heart disease: Current knowledge and future prospects","volume":"76","author":"Darby","year":"2010","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1038\/bjc.2012.575","article-title":"Radiation-related mortality from heart disease and lung cancer more than 20 years after radiotherapy for breast cancer","volume":"108","author":"Henson","year":"2013","journal-title":"Br. J. Cancer"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/j.molonc.2012.01.007","article-title":"Individualization of cancer treatment from radiotherapy perspective","volume":"6","author":"Yaromina","year":"2012","journal-title":"Mol. Oncol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1388","DOI":"10.1007\/s11864-022-01012-9","article-title":"Radiation-induced cardiovascular toxicities","volume":"23","author":"Badiyan","year":"2022","journal-title":"Curr. Treat. Options Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e021686","DOI":"10.1161\/JAHA.121.021686","article-title":"Radiation-induced cardiovascular disease: Review of an underrecognized pathology","volume":"10","author":"Eisenberg","year":"2021","journal-title":"J. Am. Heart Assoc."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1172","DOI":"10.1016\/j.ijrobp.2012.09.022","article-title":"Subclinical cardiotoxicity detected by strain rate imaging up to 14 months after breast radiation therapy","volume":"85","author":"Erven","year":"2013","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1038\/s41569-020-0348-1","article-title":"Adverse cardiac effects of cancer therapies: Cardiotoxicity and arrhythmia","volume":"17","author":"Herrmann","year":"2020","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"256","DOI":"10.33963\/KP.a2022.0066","article-title":"Radiation-induced cardiac dysfunction: Practical implications","volume":"80","author":"Pedersen","year":"2022","journal-title":"Kardiol. Pol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Zhu, D., Li, T., Zhuang, H., and Cui, M. (2022). Early detection of cardiac damage by two-dimensional speckle tracking echocardiography after thoracic radiation therapy: Study protocol for a prospective cohort study. Front. Cardiovasc. Med., 26.","DOI":"10.3389\/fcvm.2021.735265"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1136\/heartjnl-2019-315852","article-title":"Pericardial diseases in patients with cancer: Contemporary prevalence, management and outcomes","volume":"106","author":"Imazio","year":"2020","journal-title":"Heart"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1007\/s11886-019-1192-y","article-title":"Radiation-associated pericardial disease","volume":"21","author":"Szpakowski","year":"2019","journal-title":"Curr. Cardiol. Rep."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Wang, H., Wei, J., Zheng, Q., Meng, L., Xin, Y., Yin, X., and Jiang, X. (2019). Radiation-induced heart disease: A review of classification, mechanism and prevention. Int. J. Biol. Sci., 15.","DOI":"10.7150\/ijbs.35460"},{"key":"ref_14","first-page":"381","article-title":"Coronary artery disease in young women after radiation therapy for breast cancer: The WECARE Study","volume":"3","author":"Carlson","year":"2021","journal-title":"Cardio Oncol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1007\/s11883-019-0810-x","article-title":"Effects of radiotherapy in coronary artery disease","volume":"21","year":"2019","journal-title":"Curr. Atheroscler. Rep."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"251","DOI":"10.7861\/clinmed.2021-0600","article-title":"Radiation-induced coronary artery disease: A difficult clinical conundrum","volume":"22","author":"Kirresh","year":"2022","journal-title":"Clin. Med."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Aluru, J.S., Barsouk, A., Saginala, K., Rawla, P., and Barsouk, A. (2022). Valvular heart disease epidemiology. Med. Sci., 10.","DOI":"10.3390\/medsci10020032"},{"key":"ref_18","first-page":"257","article-title":"Risks of heart disease after radiotherapy","volume":"38","author":"Cutter","year":"2011","journal-title":"Tex. Heart Inst. J."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1056\/NEJMoa1209825","article-title":"Risk of ischemic heart disease in women after radiotherapy for breast cancer","volume":"368","author":"Darby","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"914","DOI":"10.3949\/ccjm.83a.15104","article-title":"Radiation-induced heart disease: A practical guide to diagnosis and management","volume":"83","author":"Donnellan","year":"2016","journal-title":"Clevel. Clin. J. Med."},{"key":"ref_21","first-page":"343","article-title":"Past, present, and future of radiation-induced cardiotoxicity: Refinements in targeting, surveillance, and risk stratification","volume":"3","author":"Bergom","year":"2021","journal-title":"Cardio Oncol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"S77","DOI":"10.1016\/j.ijrobp.2009.04.093","article-title":"Radiation dose\u2013volume effects in the heart","volume":"76","author":"Gagliardi","year":"2010","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1001\/archopht.118.3.351","article-title":"Hypertension, cardiovascular disease, and age-related macular degeneration","volume":"118","author":"Hyman","year":"2000","journal-title":"Arch. Ophthalmol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1001\/archinte.1913.00070060147012","article-title":"A clinical study of hypertensive cardiovascular disease","volume":"12","author":"Janeway","year":"1913","journal-title":"Arch. Intern. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.1161\/01.HYP.37.4.1053","article-title":"Diabetes, hypertension, and cardiovascular disease: An update","volume":"37","author":"Sowers","year":"2001","journal-title":"J. Hypertens."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/S0039-6257(01)00234-X","article-title":"Retinal microvascular abnormalities and their relationship with hypertension, cardiovascular disease, and mortality","volume":"46","author":"Wong","year":"2001","journal-title":"Surv. Ophthalmol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"3673","DOI":"10.1200\/JCO.2013.49.3205","article-title":"Modifiable risk factors and major cardiac events among adult survivors of childhood cancer","volume":"31","author":"Armstrong","year":"2013","journal-title":"J. Clin. Oncol."},{"key":"ref_28","first-page":"576","article-title":"Radio-induced cardiotoxicity: From physiopathology and risk factors to adaptation of radiotherapy treatment planning and recommended cardiac follow-up","volume":"24","author":"Kirova","year":"2020","journal-title":"Cancer Rad. Ther."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e30","DOI":"10.1161\/CIR.0000000000000556","article-title":"Cardiovascular disease and breast cancer: Where these entities intersect: A scientific statement from the American Heart Association","volume":"137","author":"Mehta","year":"2018","journal-title":"Circulation"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1016\/j.jtho.2020.11.002","article-title":"Cardiac toxicity of thoracic radiotherapy: Existing evidence and future directions","volume":"16","author":"Banfill","year":"2021","journal-title":"J. Thorac. Oncol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"36","DOI":"10.3390\/tomography9010004","article-title":"Myocardial contractility pattern characterization in radiation-induced cardiotoxicity using magnetic resonance imaging: A pilot study with ContractiX","volume":"9","author":"Ibrahim","year":"2022","journal-title":"Tomography"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e13662","DOI":"10.1111\/apha.13662","article-title":"Dietary influences on the Dahl SS rat gut microbiota and its effects on salt-sensitive hypertension and renal damage","volume":"232","author":"Saravia","year":"2021","journal-title":"Acta Physiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"F837","DOI":"10.1152\/ajprenal.90341.2008","article-title":"Chromosome substitution reveals the genetic basis of Dahl salt-sensitive hypertension and renal disease","volume":"295","author":"Mattson","year":"2008","journal-title":"Am. J. Physiol.-Ren. Physiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1291\/hypres.23.613","article-title":"Time-course changes in left ventricular geometry and function during the development of hypertension in Dahl salt-sensitive rats","volume":"23","author":"Qu","year":"2000","journal-title":"Hypertens. Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1161\/01.HYP.4.6.753","article-title":"Dahl salt-susceptible and salt-resistant rats. A review","volume":"4","author":"Rapp","year":"1982","journal-title":"J. Hypertens."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Schlaak, R.A., SenthilKumar, G., Boerma, M., and Bergom, C. (2020). Advances in preclinical research models of radiation-induced cardiac toxicity. J. Cancer, 12.","DOI":"10.3390\/cancers12020415"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1161\/HYPERTENSIONAHA.114.04179","article-title":"Maternal diet during gestation and lactation modifies the severity of salt-induced hypertension and renal injury in Dahl salt-sensitive rats","volume":"65","author":"Geurts","year":"2015","journal-title":"J. Hypertens."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1152\/physiolgenomics.00054.2008","article-title":"Substitution of Brown Norway chromosome 16 preserves cardiac function with aging in a salt-sensitive Dahl consomic rat","volume":"36","author":"Kriegel","year":"2008","journal-title":"Physiol. Genom."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"H1267","DOI":"10.1152\/ajpheart.00482.2018","article-title":"Mapping genetic modifiers of radiation-induced cardiotoxicity to rat chromosome 3","volume":"316","author":"Schlaak","year":"2019","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.mri.2020.08.020","article-title":"Optimized cardiac functional MRI of small-animal models of cancer radiation therapy","volume":"73","author":"Ibrahim","year":"2020","journal-title":"Magn. Reson. Imaging"},{"key":"ref_41","first-page":"113","article-title":"Cardiac magnetic resonance for early detection of radiation therapy-induced cardiotoxicity in a small animal model","volume":"3","author":"Ibrahim","year":"2021","journal-title":"Cardio Oncol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.mri.2018.05.008","article-title":"Regional cardiac function analysis from tagged MRI images. Comparison of techniques: Harmonic-Phase (HARP) versus Sinusoidal-Modeling (SinMod) analysis","volume":"54","author":"Ibrahim","year":"2018","journal-title":"Magn. Reson. Imaging"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1114","DOI":"10.1109\/TMI.2009.2037955","article-title":"Mapping displacement and deformation of the heart with local sine-wave modeling","volume":"29","author":"Arts","year":"2010","journal-title":"IEEE Trans. Med. Imaging"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1667\/RR15043.1","article-title":"Age at exposure to radiation determines severity of renal and cardiac disease in rats","volume":"192","author":"Lenarczyk","year":"2019","journal-title":"Radiat. Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/S0140-6736(86)90837-8","article-title":"Statistical methods for assessing agreement between two methods of clinical measurement","volume":"327","author":"Bland","year":"1986","journal-title":"Lancet"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2519","DOI":"10.1161\/HYPERTENSIONAHA.122.19316","article-title":"Knockout of the circadian clock protein PER1 (Period1) exacerbates hypertension and increases kidney injury in dahl salt-sensitive rats","volume":"79","author":"Zietara","year":"2022","journal-title":"J. Hypertens."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1104","DOI":"10.1136\/heart.89.9.1104","article-title":"Cardiac and vascular pathophysiology in hypertension","volume":"89","author":"Mayet","year":"2003","journal-title":"Heart"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1161\/01.HYP.6.4.475","article-title":"Cardiac hypertrophy and performance of Dahl hypertensive rats on graded salt diets","volume":"6","author":"Pfeffer","year":"1984","journal-title":"J. Hypertens."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1161\/01.HYP.0000215579.81408.8e","article-title":"Development of heart failure in chronic hypertensive Dahl rats: Focus on heart failure with preserved ejection fraction","volume":"47","author":"Klotz","year":"2006","journal-title":"J. Hypertens."}],"container-title":["Life"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-1729\/15\/6\/862\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:41:08Z","timestamp":1760031668000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-1729\/15\/6\/862"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,27]]},"references-count":49,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2025,6]]}},"alternative-id":["life15060862"],"URL":"https:\/\/doi.org\/10.3390\/life15060862","relation":{},"ISSN":["2075-1729"],"issn-type":[{"type":"electronic","value":"2075-1729"}],"subject":[],"published":{"date-parts":[[2025,5,27]]}}}