Department of Clinical Pharmacy, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, 211198, Jiangsu Province, People's Republic of China.
Department of Clinical Pharmacology, School of Pharmacy, Nanjing Medical University, Nanjing, 211166, Jiangsu Province, People's Republic of China.
Drug Deliv Transl Res. 2020 Feb;10(1):23-33. doi: 10.1007/s13346-019-00656-9.
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.
我们使用了一种新型主动液压心室支持药物输送系统(ASD)装置,这是一种非移植手术方法,可以附着在心脏表面,并将药物直接输送到心脏外膜。本研究旨在比较通过 ASD 和静脉注射给予硝酸甘油(NTG)对急性心肌梗死(AMI)期间缺血损伤的影响。30 只雄性 SD 大鼠分为 5 组(n = 6):假手术组、AMI 组、静脉注射组、ASD 高剂量组(ASDH)和 ASD 低剂量组(ASDL)。结扎左前降支(LAD)冠状动脉诱导心肌梗死。监测心电图,并评估血清肌红蛋白(Mb)。观察术前和术后血流动力学。进行苏木精和伊红(H&E)染色进行组织学诊断。在所有模型动物中,结扎 LAD 引起 ST 段抬高和 Mb 水平升高。在 ASDH 组,Mb 明显低于其他治疗组。ASDH 和 ASDL 组的血流动力学参数明显优于静脉注射组。H&E 染色显示 AMI 组大鼠的纤维呈波浪状,横纹消失,而 ASD 组大鼠有明显改善。与静脉注射组不同,ASD 组大鼠表现出明显的血管扩张。因此,通过 ASD 将 NTG 输送到心肌细胞可以提高治疗效果。已经证明了一种向 AMI 局部输送药物的新的有效途径。