Evaluation of azithromycin or hydroxychloroquine plus azithromycin combination therapy on cardiac conduction and function in guinea pigs
Evaluation of azithromycin or hydroxychloroquine plus azithromycin combination therapy on cardiac conduction and function in guinea pigs
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阿奇霉素或羟氯喹联合阿奇霉素联合治疗对豚鼠心脏传导和功能的评价
DOI：
10.1101/2020.10.31.362566
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发表时间：
2020-11
期刊：
影响因子：
--
通讯作者：
Feng Hua Yang
中科院分区：
文献类型：
--
作者：
Xiang Li;Weijiang Tan;Shuang Zheng;Huan Sun;Xiaosheng Zhang;Xiaohui Li;Honghua Chen;Xuecong Ren;Tianzhen He;Caiyi Zhu;Yu Zhang;Feng Hua Yang
在新冠肺炎大流行早期，抗疟药物羟氯喹（HCQ）和抗生素药物阿奇霉素（AZM）作为新兴治疗药物被广泛使用。然而，从临床试验和流行病研究中获得的有争议的心脏毒性结果表明，这两种药物的心脏毒性应重新评估。在本研究中，我们旨在评估短疗程AZM或HCQ + AZM联合治疗对健康豚鼠心电图和心功能的影响。方法32只雄性豚鼠随机分为4组：对照组；AZM;HCQ;和HCQ + AZM组。在治疗后3、6和9天，采用心电图（ECGs）和超声心动图技术确定左心室的重要心电图参数和心功能参数（包括后壁厚度、收缩期末/舒张期末容积、射血分数和分数缩短）。结果AZM在麻醉条件下降低豚鼠第9天的心率，HCQ + AZM在第3、6、9天降低心率。与CON和HCQ处理相比，AZM和HCQ + AZM处理豚鼠在第3、6和9天的校正QT间期显著增加。然而，QRS复杂持续时间组间无显著差异。AZM在第3,6和9天显著降低左室射血分数（LVEF）和左室缩短分数（LVFS），而HCQ + AZM仅在第9天降低LVEF和LVFS。舒张期和收缩期左心室后壁厚度和左心室壁厚度在两组间无显著差异。此外，与CON相比，AZM和HCQ降低了EDV。与HCQ处理相比，HCQ + AZM处理提高了第9天的ESV。结论AZM明显延长QT间期，损害心功能。此外，与HCQ治疗相比，HCQ + AZM治疗增加了心功能障碍的风险。
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.
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影响因子：
3.4
作者：
McGowan JV;Chung R;Maulik A;Piotrowska I;Walker JM;Yellon DM
通讯作者：
Yellon DM
DOI：
10.1016/0160-5402(89)90015-6
发表时间：
1989-11-01
期刊：
JOURNAL OF PHARMACOLOGICAL METHODS
影响因子：
--
作者：
VANDEWATER, A;VERHEYEN, J;RENEMAN, RS
通讯作者：
RENEMAN, RS
影响因子：
158.5
作者：
Cavalcanti, A. B.;Zampieri, F. G.;Berwanger, O.
通讯作者：
Berwanger, O.
影响因子：
18.2
作者：
Davey, P
通讯作者：
Davey, P
影响因子：
37.8
作者：
NADOR, F;BERIA, G;SCHWARTZ, PJ
通讯作者：
SCHWARTZ, PJ