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An epicardial delivery of nitroglycerine by active hydraulic ventricular support drug delivery system improves cardiac function in a rat model

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Abstract

We have used a novel active hydraulic ventricular support drug delivery system (ASD) device, which is a non-transplant surgical approach, can adhere to heart surface, and deliver the drug directly into the epicardium. This study is intended to compare the effect of administration of nitroglycerine (NTG) through ASD and intravenous injection on the ischemic injury during acute myocardial infarction (AMI). 30 male SD rats were allocated into five groups (n = 6): sham, AMI, I.V., ASD high dose (ASDH), and ASD low dose (ASDL) respectively. Ligation of the left anterior descending (LAD) coronary artery was performed to induce myocardial infarction. Electrocardiograms were monitored, and serum myoglobin (Mb) was assessed. Hemodynamics was observed on pre- and post-operation. Hematoxylin and eosin (H&E) staining was performed for histological diagnosis. In all model animals, ligation of LAD provoked ST segment elevation and Mb level augmentation. In ASDH group, Mb showed obvious decrease as compared with other treatment groups. Hemodynamic parameters showed significant improvement in ASDH and ASDL groups than the I.V. group. H&E staining showed that AMI group rats had wavy fibers and loss of transverse striations while ASD group rats had obvious improvement. Unlike the I.V. group, ASD group rats showed significant vasodilation. Therefore, delivery of NTG through ASD to the cardiomyocytes could improve the therapeutic efficacy. A novel effective route for local delivery of agents to manage AMI has been proved.

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Funding

This work was supported by the National Found for Fostering Talents of Basic Science (NFFTBS), [grant number J1030830], the National Natural Science Foundation of China [grant numbers 30973003; 30901993], and the Administration of TCM of Jiangsu Province [grant number LZ11093].

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Authors and Affiliations

  1. Department of Clinical Pharmacy, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, 211198, Jiangsu Province, People’s Republic of China

    Xue Li, Reyaj Mikrani, Cunyu Li, Ziwei Liu, Yijie Cheng & Xiaohui Zhou

  2. Department of Clinical Pharmacology, School of Pharmacy, Nanjing Medical University, Nanjing, 211166, Jiangsu Province, People’s Republic of China

    Muhammad Naveed

  3. State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, 210023, Jiangsu Province, China

    Muhammad Abbas

  4. Department of Pharmacy, Jiangsu Health Vocational College, Nanjing, 211800, Jiangsu Province, People’s Republic of China

    Lei Han

  5. Key Laboratory of Semiconductor Materials Science, Institute of Semiconductors, Chinese Academy of Sciences, Beijing, 100083, People’s Republic of China

    Zhijie Wang

  6. Department of Surgery, Zhongda Hospital, Southeast University, Nanjing, 210017, Jiangsu Province, People’s Republic of China

    Xiaohui Zhou

  7. Department of Surgery, Nanjing Shuiximen Hospital, Nanjing, 210017, Jiangsu Province, People’s Republic of China

    Xiaohui Zhou

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  1. Xue Li
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Xue Li and Reyaj Mikrani are co-first authors

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Li, X., Mikrani, R., Li, C. et al. An epicardial delivery of nitroglycerine by active hydraulic ventricular support drug delivery system improves cardiac function in a rat model. Drug Deliv. and Transl. Res. 10, 23–33 (2020). https://doi.org/10.1007/s13346-019-00656-9

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