Nicorandil Ameliorates Doxorubicin-Induced Cardiotoxicity in Rats, as Evaluated by 7 T Cardiovascular Magnetic Resonance Imaging

Figures

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  Fig. 1. Study design

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  Fig. 2. Body weight of the rats in the control, Nic, Dox, Dox + Nic, and Dox + DZ groups at different time points. The data are expressed as means ± SD

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  Fig. 3. Effect of nicorandil on doxorubicin-induced cardiac injury. (A) Representative gross images of the whole heart. (B) Representative images of HE staining in the left ventricles (LV) of the five groups (×400) (n = 5–8). (C) CK, CK-MB, and LDH levels in the five groups measured by ELISA (n = 5–8). (D) Late gadolinium enhancement (LGE) images (red arrow, hyperintense). The data are expressed as means ± SD. ***p < 0.001 versus control. ###p < 0.001 versus Dox

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  Fig. 4. Nicorandil treatment improves cardiac function. (A) Representative diastolic and systolic CMR images of the left ventricles from five groups at week 6 (n = 5–8) (red arrow, pericardial effusion). (B) Progression of the LVEF during the protocol (n = 5–8). (C–E) Progression of the LVM (C), LVEDV (D) and LVESV (E) during the protocol (n = 5–8). The data are expressed as means ± SD. LVEF, left ventricular ejection fraction; LVM, left ventricular mass; LVEDV, left ventricular end-diastolic volume; LVESV, left ventricular end-systolic volume

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  Fig. 5. Nicorandil treatment reduces myocardial oedema. (A) Representative images of T2 mapping in the five groups at week 2 (n = 5–8) (red arrow, hyperintense). (B) Progression of T2 mapping during the protocol (n = 5–8). The data are expressed as means ± SD

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  Fig. 6. Nicorandil treatment improves cardiac strain. (A) Representative short-axis strain and 2,4-chamber long-axis strain images. (B) GLS, GRS and GCS at 6 weeks (n = 5–8) (C) Representative strain time curves of the five groups at 6 weeks. GLS, global peak longitudinal strain; GRS, global peak radial strain; GCS, global peak circumferential strain; LV, left ventricle. The data are expressed as means ± SD. ***p < 0.001 versus control. ##p < 0.01, ###p < 0.001 versus Dox

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  Fig. 7. Effects of nicorandil on myocardial fibrosis and apoptosis. (A) Representative Masson’s trichrome staining images illustrating myocardial interstitial fibrosis at 6 weeks (×400) (n = 5–8). (B) Cell apoptosis as determined by the TUNEL assay (n = 5): apoptotic cells stained green; nuclei stained blue with DAPI. (C) Quantification of the relative fibrotic area by Masson’s trichrome staining (n = 5–8). (D) The apoptosis rate was determined by the TUNEL assay (n = 5). The data are expressed as means ± SD. ***p < 0.001 versus control. ###p < 0.001 versus Dox

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  Fig. 8. Nicorandil treatment attenuates the inflammatory response. (A) NLRP3 expression in the five groups as visualized by IHC (×400) (n = 5). (B) IL-1β, IL-18 and TNF-α levels in the five groups as measured by ELISA (n = 5). The data are expressed as means ± SD. ***p < 0.001 versus control. ###p < 0.001 versus Dox