ORIGINAL ARTICLE An epicardial delivery of nitroglycerine by active hydraulic ventricular support drug delivery system improves cardiac function in a rat model Xue Li 1 & Reyaj Mikrani 1 & Cunyu Li 1 & Muhammad Naveed 2 & Ziwei Liu 1 & Muhammad Abbas 3 & Yijie Cheng 1 & Lei Han 4 & Zhijie Wang 5 & Xiaohui Zhou 1,6,7 # Controlled Release Society 2019 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. Keywords Myocardial infarction . Local cardiac drug delivery . Hemodynamics . Nitroglycerin . Active hydraulic ventricular support drug delivery system (ASD) Xue Li and Reyaj Mikrani are co-first authors Lei Han, Zhijie Wang and Xiaohui Zhou are co-corresponding authors * Xiaohui Zhou zhxh@cpu.edu.cn 1 Department of Clinical Pharmacy, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing 211198, Jiangsu Province, Peoples Republic of China 2 Department of Clinical Pharmacology, School of Pharmacy, Nanjing Medical University, Nanjing 211166, Jiangsu Province, Peoples Republic of China 3 State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210023, Jiangsu Province, China 4 Department of Pharmacy, Jiangsu Health Vocational College, Nanjing 211800, Jiangsu Province, Peoples Republic of China 5 Key Laboratory of Semiconductor Materials Science, Institute of Semiconductors, Chinese Academy of Sciences, Beijing 100083, Peoples Republic of China 6 Department of Surgery, Zhongda Hospital, Southeast University, Nanjing 210017, Jiangsu Province, Peoples Republic of China 7 Department of Surgery, Nanjing Shuiximen Hospital, Nanjing 210017, Jiangsu Province, Peoples Republic of China Drug Delivery and Translational Research https://doi.org/10.1007/s13346-019-00656-9