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

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.

[Expression patterns of ectodysplasin and ectodysplasin receptor during early dental development in zebrafish].

OBJECTIVE: This study aims to study the expression patterns of ectodysplasin (EDA) and ectodysplasin receptor (EDAR) during the early development of zebrafish and provide a foundation for further research of the Eda signaling pathway in tooth development. METHODS: Total RNA was extracted from zebrafish embryos at 48 hours postfertilization (hpf) and then reverse transcribed for cDNA library generation. The corresponding RNA polymerase was selected for the synthesis of the digoxin-labeled antisense mRNA probe of zebrafish pharyngeal tooth specific marker dlx2b and Eda signaling-associated genes eda and edar in vitro. The three sequences were ligated into a pGEMT vector with a TA cloning kit, and polymerase chain reaction (PCR) was applied to linearize the plasmid. The resultant PCR sequences were used as templates for synthesizing Dig-labeled mRNA probe dlx2b, eda, and edar. Zebrafish embryos were collected at 36, 48, 56, 60, 72, and 84 hpf, then whole mount in situ hybridization was performed for the detection of eda and edar expression patterns. Then, their expression patterns at 72 hpf were compared with the expression pattern of dlx2b. RESULTS: The mRNA antisense probes of dlx2b, eda, and edar were successfully obtained. The positive signals of eda and edar were observed in zebrafish pharyngeal tooth region at 48-72 hpf and thus conform to the signals of dlx2b in the positive regions. CONCLUSIONS: The ligand eda and edar, which are associated with the Eda signaling pathway, are strongly expressed only at the pharyngeal tooth region in zebrafish from tooth initiation to the morphogenesis stage. Thus, the Eda signaling pathway may be involved in the regulation of the early development of zebrafish pharyngeal teeth.

Does PGA external stenting reduce compliance mismatch in venous grafts?

BACKGROUND: Autogenous vein grafting is widely used in regular bypassing procedures. Due to its mismatch with the host artery in both mechanical property and geometry, the graft often over expands under high arterial blood pressure and forms a step-depth where eddy flow develops, thus causing restenosis, fibrous graft wall, etc. External stents, such as sheaths being used to cuff the graft, have been introduced to eliminate these mismatches and increase the patency. Although histological and immunochemical studies have shown some positive effects of the external stent, the mechanical mismatch under the protection of an external stent remains poorly analyzed. METHODS: In this study, the jugular veins taken from hypercholesterolemic rabbits were transplanted into the carotid arteries, and non-woven polyglycolic acid (PGA) fabric was used to fabricate the external stents to study the effect of the biodegradable external stent. Eight weeks after the operation, the grafts were harvested to perform mechanical tests and histological examinations. An arc tangent function was suggested to describe the relationship between pressure and cross-sectional area to analyse the compliance of the graft. RESULTS: The results from the mechanical tests indicated that grafts either with or without external stents displayed large compliance in the low-pressure range and were almost inextensible in the high-pressure range. This was very different from the behavior of the arteries or veins in vivo. The data from histological tests showed that, with external stents, collagen fibers were more compact, whilst those in the graft without protection were looser and thicker. No elastic fiber was found in either kind of grafts. Furthermore, grafts without protection were over-expanded which resulted in much bigger cross-sectional areas. CONCLUSION: The PGA external extent contributes little to the reduction of the mechanical mismatch between the graft and its host artery while remodeling develops. For the geometric mismatch, it reduces the cross-section area, therefore matching with the host artery much better. Although there are some positive effects, conclusively the PGA is not an ideal material for external stent.

Transcatheter pulmonary valve replacement by hybrid approach using a novel polymeric prosthetic heart valve: proof of concept in sheep.

BACKGROUND: Since 2000, transcatheter pulmonary valve replacement has steadily advanced. However, the available prosthetic valves are restricted to bioprosthesis which have defects like poor durability. Polymeric heart valve is thought as a promising alternative to bioprosthesis. In this study, we introduced a novel polymeric transcatheter pulmonary valve and evaluated its feasibility and safety in sheep by a hybrid approach. METHODS: We designed a novel polymeric trileaflet transcatheter pulmonary valve with a balloon-expandable stent, and the valve leaflets were made of 0.1-mm expanded polytetrafluoroethylene (ePTFE) coated with phosphorylcholine. We chose glutaraldehyde-treated bovine pericardium valves as control. Pulmonary valve stents were implanted in situ by a hybrid transapical approach in 10 healthy sheep (8 for polymeric valve and 2 for bovine pericardium valve), weighing an average of 22.5±2.0 kg. Angiography and cardiac catheter examination were performed after implantation to assess immediate valvular functionality. After 4-week follow-up, angiography, echocardiography, computed tomography, and cardiac catheter examination were used to assess early valvular function. One randomly selected sheep with polymeric valve was euthanized and the explanted valved stent was analyzed macroscopically and microscopically. FINDINGS: Implantation was successful in 9 sheep. Angiography at implantation showed all 9 prosthetic valves demonstrated orthotopic position and normal functionality. All 9 sheep survived at 4-week follow-up. Four-week follow-up revealed no evidence of valve stent dislocation or deformation and normal valvular and cardiac functionality. The cardiac catheter examination showed the peak-peak transvalvular pressure gradient of the polymeric valves was 11.9±5.0 mmHg, while that of two bovine pericardium valves were 11 and 17 mmHg. Gross morphology demonstrated good opening and closure characteristics. No thrombus or calcification was seen macroscopically. CONCLUSIONS: This design of the novel ePTFE transcatheter pulmonary valve is safe and effective to deploy in sheep by hybrid approach, and the early valvular functionality is good.