Background In the early stages of the coronavirus disease pandemic, the anti-malarial drug hydroxychloroquine (HCQ) and the antibiotic drug azithromycin (AZM) were widely used as emerging treatments. However, controversial cardiac toxicity results obtained from clinical trials and epidemic studies suggest that the cardiotoxicity of these two drugs should be re-evaluated. In the present study, we aimed to assess the impact of a short course of AZM or HCQ + AZM combination treatment on ECG and cardiac function in healthy guinea pigs. Methods Thirty-two male guinea pigs were randomly divided into four groups: control; AZM; HCQ; and HCQ + AZM groups. At 3, 6, and 9 days after treatment, electrocardiograms (ECGs) and echocardiographic techniques were used to determine important ECG parameters and cardiac functional parameters of the left ventricle (including posterior wall thickness, end systolic/end diastolic volume, ejection fraction, and fractional shortening). Results Although AZM decreased the heart rates of guinea pigs on day 9 (under anesthetized conditions), HCQ + AZM decreased heart rates on days 3, 6, and 9. The corrected QT intervals of guinea pigs after AZM and HCQ + AZM treatments were significantly increased, compared with CON and HCQ treatment respectively, on days 3, 6, and 9. However, QRS complex durations were not significantly different between the groups. AZM significantly decreased left ventricular ejection fraction (LVEF) and left ventricular fraction shortening (LVFS) on days 3, 6, and 9, whereas HCQ + AZM only decreased LVEF and LVFS on day 9. Posterior wall thickness and of the left ventricle in the diastolic and systolic states were not significantly different between these groups. In addition, compared with CON, AZM and HCQ decreased the EDV. And, in comparison with HCQ treatment, HCQ + AZM treatment increased ESV on day 9. Conclusions According to our study, AZM significantly prolongs the QT interval and damages cardiac function. Moreover, HCQ + AZM treatment increased the risk of cardiac dysfunction compared with HCQ treatment.

中文翻译：

---

阿奇霉素或羟氯喹加阿奇霉素联合治疗对豚鼠心脏传导和功能的评价

背景技术在冠状病毒大流行的早期阶段，抗疟疾药物羟氯喹（HCQ）和抗生素药物阿奇霉素（AZM）被广泛用作新兴治疗方法。但是，从临床试验和流行病学研究获得的有争议的心脏毒性结果表明，应重新评估这两种药物的心脏毒性。在本研究中，我们旨在评估短期AZM或HCQ + AZM联合治疗对健康豚鼠ECG和心脏功能的影响。方法将32只豚鼠随机分为4组：对照组; AZM；HCQ；以及HCQ + AZM组。治疗后第3、6和9天，心电图（ECG）和超声心动图技术用于确定左心室的重要ECG参数和心脏功能参数（包括后壁厚度，收缩末期/舒张末期容积，射血分数和缩短分数）。结果尽管AZM在麻醉后第9天降低了豚鼠的心率，但是HCQ + AZM在第3、6和9天降低了心率。AZM和HCQ + AZM治疗后，豚鼠的校正QT间隔显着在第3天，第6天和第9天，与CON和HCQ治疗相比分别增加。但是，两组之间QRS复杂持续时间无显着差异。在第3、6和9天，AZM显着降低左心室射血分数（LVEF）和缩短左心室分数（LVFS）。而HCQ + AZM仅在第9天降低LVEF和LVFS。在这两组之间，后壁厚度以及舒张期和收缩期左心室的厚度没有显着差异。此外，与CON相比，AZM和HCQ降低了EDV。并且，与HCQ治疗相比，HCQ + AZM治疗在第9天增加了ESV。结论根据我们的研究，AZM显着延长了QT间隔并损害了心功能。此外，与HCQ治疗相比，HCQ + AZM治疗增加了心脏功能障碍的风险。HCQ + AZM治疗在第9天增加了ESV。结论根据我们的研究，AZM显着延长了QT间隔并损害了心脏功能。此外，与HCQ治疗相比，HCQ + AZM治疗增加了心脏功能障碍的风险。HCQ + AZM治疗在第9天增加了ESV。结论根据我们的研究，AZM显着延长了QT间隔并损害了心脏功能。此外，与HCQ治疗相比，HCQ + AZM治疗增加了心脏功能障碍的风险。