Purpose

Doxorubicin-induced cardiotoxicity (DIC) is a common side effect of doxorubicin chemotherapy, and a major mechanism of DIC is inflammation. However, no effective method exists to prevent DIC. In the present study, we investigated the cardioprotective effects of nicorandil against DIC using multiparametric cardiac magnetic resonance (CMR) imaging and elucidated the anti-inflammatory properties of nicorandil in rat models.

Methods

Male Sprague-Dawley rats received four weekly intraperitoneal doxorubicin doses (4 mg/kg/injection) to establish the DIC model. After treatment with or without nicorandil (3 mg/kg/day) or diazoxide (10 mg/kg/day) orally, all the groups underwent weekly CMR examinations, including cardiac function and strain assessment and T2 mapping, for 6 weeks. Additionally, blood samples and hearts were collected to examine inflammation and histopathology.

Results

According to our results, the earliest DIC CMR parameter in the doxorubicin group was T2 mapping time prolongation compared with the DIC rats treated with nicorandil (doxorubicin+nicorandil group) at week 2. Subsequently, the left ventricular ejection fraction (LVEF) and global peak systolic myocardial strain in the doxorubicin group were significantly reduced, and nicorandil effectively inhibited these effects at week 6. Our results were confirmed by histopathological evaluations. Furthermore, nicorandil treatment had a protective effect against the doxorubicin-induced inflammatory response. Interestingly, similar protective results were obtained using the K_ATP channel opener diazoxide.

Conclusion

Collectively, our findings indicate that nicorandil application ameliorates DIC in rats with significantly higher cardiac function and myocardial strain and less fibrosis, apoptosis and inflammatory cytokine production. Nicorandil prevents T2 abnormalities in the early stages of DIC, showing a high clinical value for early nicorandil treatment in chemotherapy patients.

中文翻译：

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7 T 心血管磁共振成像评估尼可地尔可改善多柔比星诱导的大鼠心脏毒性

目的

阿霉素诱导的心脏毒性（DIC）是阿霉素化疗的常见副作用，DIC的主要机制是炎症。然而，目前尚无预防 DIC 的有效方法。在本研究中，我们使用多参数心脏磁共振 (CMR) 成像研究了尼可地尔对 DIC 的心脏保护作用，并阐明了尼可地尔在大鼠模型中的抗炎特性。

方法

雄性 Sprague-Dawley 大鼠每周接受四次腹膜内阿霉素剂量（4 mg/kg/注射）以建立 DIC 模型。在口服或不口服尼可地尔（3 mg/kg/天）或二氮嗪（10 mg/kg/天）治疗后，所有组均接受为期 6 周的每周 CMR 检查，包括心脏功能和应变评估以及 T2 映射。此外，还收集了血液样本和心脏以检查炎症和组织病理学。

结果

根据我们的结果，与第 2 周用尼可地尔治疗的 DIC 大鼠（多柔比星 + 尼可地尔组）相比，多柔比星组最早的 DIC CMR 参数是 T2 映射时间延长。随后，左心室射血分数（LVEF）和全局峰值阿霉素组的收缩期心肌应变显着降低，而尼可地尔在第 6 周时有效抑制了这些作用。组织病理学评估证实了我们的结果。此外，尼可地尔治疗对多柔比星诱导的炎症反应具有保护作用。有趣的是，使用 K _ATP通道开启剂二氮嗪获得了类似的保护结果。

结论

总的来说，我们的研究结果表明，尼可地尔的应用改善了大鼠的 DIC，其心功能和心肌应变显着更高，纤维化、细胞凋亡和炎性细胞因子的产生更少。尼可地尔可预防DIC早期T2异常，对化疗患者早期尼可地尔治疗具有较高的临床价值。