An Zhao, Wu Jun, Li Shu-Hong, Chen Shanglin, Lu Fang-Lin, Xu Zhi-Yun, Sung Hsing-Wen, Li Ren-Ke
Toronto General Hospital Research Institute, Division of Cardiovascular Surgery, University Health Network, Toronto, Ontario, Canada.
Department of Cardiovascular Surgery, Changhai Hospital, Naval Medical University, Shanghai, China.
Theranostics. 2021 Feb 6;11(8):3948-3960. doi: 10.7150/thno.54959. eCollection 2021.
Pacemaker implantation is currently used in patients with symptomatic bradycardia. Since a pacemaker is a lifetime therapeutic device, its energy consumption contributes to battery exhaustion, along with its voltage stimulation resulting in local fibrosis and greater resistance, which are all detrimental to patients. The possible resolution for those clinical issues is an injection of a conductive hydrogel, poly-3-amino-4-methoxybenzoic acid-gelatin (PAMB-G), to reduce the myocardial threshold voltage for pacemaker stimulation. PAMB-G is synthesized by covalently linking PAMB to gelatin, and its conductivity is measured using two-point resistivity. Rat hearts are injected with gelatin or PAMB-G, and pacing threshold is evaluated using electrocardiogram and cardiac optical mapping. PAMB-G conductivity is 13 times greater than in gelatin. The model shows that PAMB-G significantly enhances cardiac tissue stimulation. Injection of PAMB-G into the stimulating electrode location at the myocardium has a 4 times greater reduction of pacing threshold voltage, compared with electrode-only or gelatin-injected tissues. Multi-electrode array mapping reveals that the cardiac conduction velocity of PAMB-G group is significantly faster than the non- or gelatin-injection groups. PAMB-G also reduces pacing threshold voltage in an adenosine-induced atrial-ventricular block rat model. PAMB-G hydrogel reduces cardiac pacing threshold voltage, which is able to enhance pacemaker efficacy.
目前，起搏器植入用于有症状的心动过缓患者。由于起搏器是一种终身治疗设备，其能量消耗会导致电池耗尽，同时其电压刺激会导致局部纤维化和更大的电阻，这些对患者都是有害的。解决这些临床问题的可能方法是注射一种导电水凝胶，即聚-3-氨基-4-甲氧基苯甲酸-明胶（PAMB-G），以降低起搏器刺激的心肌阈值电压。PAMB-G是通过将PAMB与明胶共价连接合成的，其电导率使用两点电阻率测量。向大鼠心脏注射明胶或PAMB-G，并使用心电图和心脏光学映射评估起搏阈值。PAMB-G的电导率比明胶高13倍。该模型表明，PAMB-G能显著增强心脏组织刺激。与仅植入电极或注射明胶的组织相比，在心肌刺激电极位置注射PAMB-G可使起搏阈值电压降低4倍。多电极阵列映射显示，PAMB-G组的心脏传导速度明显快于未注射或注射明胶的组。PAMB-G还能降低腺苷诱导的房室传导阻滞大鼠模型的起搏阈值电压。PAMB-G水凝胶可降低心脏起搏阈值电压，从而提高起搏器疗效。
