Adverse cardiovascular effects of antiretrovirals in female mice  during gestation

doi:10.12047/j.cjap.6192.2022.038

CJAP ›› 2022, Vol. 38 ›› Issue (3): 252-257.doi: 10.12047/j.cjap.6192.2022.038

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Adverse cardiovascular effects of antiretrovirals in female mice during gestation

YU Hai-juan^1,2, CHEN Zu-sheng¹, CHEN Tong², WU Yi-jing², SUN Ke-yue², LI Yu-jing², XU Qin³, YE Han-hui⁴, CHEN Ya-hong⁴, RUAN Qin-yun⁵, FU Li-yun⁵, HUANG Chun-yan⁵, ZHOU Lin-ying⁶, WANG Min-hua⁷, FANG Qiu-juan^1△

1. The Key Laboratory of Fujian Province University on Ion Channel and Signal Transduction in Cardiovascular Disease, Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fujian Medical University;
2. Department of Clinical Medicine, Fujian Medical University;
3. School of Nursing, Fujian Medical University;
4. Mengchao Hepatobiliary Hospital of Fujian Medical University;
5. Department of Ultrasound, The First Affiliated Hospital of Fujian Medical University;
6. Electron Microscopy Lab of Public Technology Service Center, Fujian Medical University;
7. Department of Obstetrics and Gynecology, the Second Affiliated Hospital of Fujian University of Traditional Chinese Medicine, Fuzhou 350108, China

Received:2021-03-18 Revised:2022-05-03 Online:2022-05-28 Published:2022-09-05

Abstract

Abstract: Objective: To evaluate the effects of antiretrovirals on cardiovascular function and some biochemical indexes in gestational female rats. Methods: Nineteen 9-week-old female and six 10-week-old male SD rats were divided into normal control group (CON) and highly active antiretroviral therapy group (HARRT), 9/10 female rats and 3 male rats were combined into one cage, totally 2 cages. Female rats in CON group were intragastrically given with normal saline (NS, 10 ml/kg) every morning and evening, while female rats in HARRT group were treated with equal volume antiretrovirals (AZT 31.25 mg/kg + 3TC 15.63 mg/kg + LPV/r (41.67/10.42) mg/kg) for 3 months. The body weight and survival rate of female rats were recorded. Echocardiography and multichannel physiological recorder were used to detect arterial blood pressure and cardiac hemodynamic parameters. The levels of blood glucose, blood lipids, myocardial enzymes and liver enzymes were detected by corresponding kits. Myocardial collagen fibers were observed by Masson staining and the ultrastructure of myocardial cells were observed by transmission electron microscopy. Results: All female rats in CON group survived (9/9), while only 6 rats in HARRT group survived (6/10). Compared with CON group, the body weight of female rats in HAART group was decreased significantly(P＜0.01); the levels of left ventricular end diastolic diameter (LVDd), interventricular septal thickness (IVST), thickness of left ventricular posterior wall (LVPWT) , left atrial diameter (LAD) and arterial diastolic pressure were increased significantly (P＜0.05); the level of LVP+dP/dtmax was decreased (P＜0.01). The levels of triglyceride, creatine kinase, and glutamic oxaloacetic transaminase were decreased (P＜0.05 or P＜0.01), while the level of glucose was increased (P＜0.05). The collagen fibers were increased in myocardial tissue, and ultrastructure of myocardial cells was abnormal. Conclusion: Antiretrovirals during gestation can cause cardiovascular diseases in female rats.

Key words: female rats, gestational period, highly active anti-retroviral therapy, adverse cardiovascular reactions

CLC Number:

R363.3+3

YU Hai-juan, CHEN Zu-sheng, CHEN Tong, WU Yi-jing, SUN Ke-yue, LI Yu-jing, XU Qin, YE Han-hui, CHEN Ya-hong, RUAN Qin-yun, FU Li-yun, HUANG Chun-yan, ZHOU Lin-ying, WANG Min-hua, FANG Qiu-juan. Adverse cardiovascular effects of antiretrovirals in female mice during gestation[J]. CJAP, 2022, 38(3): 252-257.

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Adverse cardiovascular effects of antiretrovirals in female mice during gestation

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