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Injectable conductive hydrogel can reduce pacing threshold and enhance efficacy of cardiac pacemaker.

ABSTRACT: Background: 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. Methods: 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. Results: PAMB-G conductivity is 13 times greater than in gelatin. The ex vivo 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. Conclusion: PAMB-G hydrogel reduces cardiac pacing threshold voltage, which is able to enhance pacemaker efficacy.

SUBMITTER: An Z

PROVIDER: S-EPMC7914366 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Injectable conductive hydrogel can reduce pacing threshold and enhance efficacy of cardiac pacemaker.

An Zhao Z Wu Jun J Li Shu-Hong SH Chen Shanglin S Lu Fang-Lin FL Xu Zhi-Yun ZY Sung Hsing-Wen HW Li Ren-Ke RK

Theranostics 20210206 8

<b>Background:</b> 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 myo ...[more]

PMID: 33664872

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Project description:Myocardial infarction (MI) causes irreversible damage to the heart muscle, seriously threatening the lives of patients. Injectable hydrogels have attracted extensive attention in the treatment of MI. By promoting the coupling of mechanical and electrical signals between cardiomyocytes, combined with synergistic therapeutic strategies targeting the pathological processes of inflammation, proliferation, and fibrotic remodeling after MI, it is expected to improve the therapeutic effect. In this study, a pH/ROS dual-responsive injectable hydrogel was developed by modifying xanthan gum and gelatin with reversible imine bond and boronic ester bond double crosslinking. By encapsulating polydopamine-rosmarinic acid nanoparticles to achieve on-demand drug release in response to the microenvironment of MI, thereby exerting anti-inflammatory, anti-apoptotic, and anti-fibrosis effects. By adding conductive composites to improve the conductivity and mechanical strength of the hydrogel, restore electrical signal transmission in the infarct area, promote synchronous contraction of cardiomyocytes, avoid induced arrhythmias, and induce angiogenesis. Furthermore, the multifunctional hydrogel promoted the expression of cardiac-specific markers to restore cardiac function after MI. The in vivo and in vitro results demonstrate the effectiveness of this synergistic comprehensive treatment strategy in MI treatment, showing great application potential to promote the repair of infarcted hearts. Graphical abstract Image 1 Highlights • An injectable self-healing conductive hydrogel with pH/ROS dual-responsive drug release was prepared for the treatment of MI.• The OGDPR hydrogel has conductivity (6.27 × 10−4 S/cm) and elastic modulus (45.35 kPa) matching those of the natural heart.• The biocompatible hydrogel can resist oxidation, promote macrophage polarization and tube formation of endothelial cells.• The hydrogel can protect cardiac function, reduce arrhythmia susceptibility, and reduce infarct size and fibrosis after MI.• The hydrogel can reduce apoptosis and inflammation, and promote angiogenesis and the expression of cardiac-specific markers.

Project description:The use of temporary cardiac pacing is frequent in critical care units for severe bradycardia or electrical storm, but may be associated with frequent and potentially severe complications, especially when indwelling for several days. In some cases, transient indication or ongoing contraindication for a permanent pacemaker justifies prolonged temporary pacing. In that case, the implantation of an active-fixation lead connected to an externalized pacemaker represents a valuable option to increase safety and patient comfort. Yet, evidence remains scarce. We aimed to describe the population receiving prolonged temporary cardiac pacing (PTCP) and their outcomes. We retrospectively included all consecutive patients, admitted to our hospital from 2016 to 2021, who underwent PTCP. We collected in-hospital and six-month outcomes. Forty-six patients (median age of 73, 63% male) were included, and twenty-nine (63%) had prior heart disease. Indications for PTCP were found: seventeen (37%) potentially reversible high-grade conduction disorders, fourteen (30%) indications for permanent pacemaker but ongoing infection, seven (15%) cardiac implantable electronic device infections requiring extraction in pacing-dependent patients, seven (15%) severe vagal hyperreactivity in prolonged critical care hospitalizations, and one (2%) recurrent sustained ventricular tachycardia requiring overdrive pacing. The median PTCP duration was nine (5-13) days. Ten (22%) patients exhibited at least one complication during hospitalization. Twenty-six (56.5%) patients required definite device implantation (twenty-five pacemakers and one cardioverter-defibrillator) and twenty (43.5%) did not (fifteen PTCP device removal for recovery and five deaths under PTCP). At six months, two (5%) deaths and two (5%) new infections of a definite implanted device occurred, all in patients with initial active infection. The use of prolonged temporary cardiac pacing, with an active -fixation lead connected to an externalized pacemaker, is possible and reasonable; this would allow for the possible recovery or resolution of contraindication for definite device implantation.

Project description:The objective of this study was to develop an injectable and biocompatible hydrogel that can deliver a cocktail of therapeutic biomolecules (secretome) secreted by human adipose-derived stem cells (hASCs) to the peri-infarct myocardium. Gelatin and Laponite® were combined to formulate a shear-thinning, nanocomposite hydrogel (nSi Gel) as an injectable carrier of secretome (nSi Gel+). The growth factor composition and the pro-angiogenic activity of the secretome were tested in vitro by evaluating the proliferation, migration and tube formation of human umbilical endothelial cells. The therapeutic efficacy of the nSi Gel + system was then investigated in vivo in rats by intramyocardial injection into the peri-infarct region. Subsequently, the inflammatory response, angiogenesis, scar formation, and heart function were assessed. Biocompatibility of the developed nSi Gel was confirmed by quantitative PCR and immunohistochemical tests which showed no significant differences in the level of inflammatory genes, microRNAs, and cell marker expression compared to the untreated control group. In addition, the only group that showed a significant increase in capillary density, reduction in scar area and improved cardiac function was treated with the nSi Gel+. Our in vitro and in vivo findings demonstrate the potential of this new secretome-loaded hydrogel as an alternative strategy to treat myocardial infarction.Statement of significanceStem cell based-therapies represent a possible solution to repair damaged myocardial tissue by promoting cardioprotection, angiogenesis, and reduced fibrosis. However, recent evidence indicates that most of the positive outcomes are likely due to the release of paracrine factors (cytokines, growth factors, and exosomes) from the cells and not because of the local engraftment of stem cells. This cocktail of essential growth factors and paracrine signals is known as secretome can be isolated in vitro, and the biomolecule composition can be controlled by varying stem-cell culture conditions. Here, we propose a straightforward strategy to deliver secretome produced from hASCs by using a nanocomposite injectable hydrogel made of gelatin and Laponite®. The designed secretome-loaded hydrogel represents a promising alternative to traditional stem cell therapy for the treatment of acute myocardial infarction.

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Injectable conductive hydrogel can reduce pacing threshold and enhance efficacy of cardiac pacemaker.

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Injectable conductive hydrogel can reduce pacing threshold and enhance efficacy of cardiac pacemaker.

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