A pilot clinical assessment of biphasic asymmetric pulsed field ablation catheter for pulmonary vein isolation.

Pulsed field ablation (PFA) is a new treatment for atrial fibrillation (AF), and its selective ablation characteristics give it a significant advantage in treatment. In previous cellular and animal experiments, we have demonstrated that biphasic asymmetric pulses can be used to ablate myocardial tissue. However, small-scale clinical trials are needed to test whether this approach is safe and feasible before extensive clinical trials can be performed. Therefore, the purpose of this experiment is to determine the safety and feasibility of biphasic asymmetric pulses in patients with AF and is to lay the foundation for a larger clinical trial. Ablation was performed in 10 patients with AF using biphasic asymmetric pulses. Voltage mapping was performed before and after PFA operation to help us detect the change in the electrical voltage of the pulmonary veins (PV). 3-Dimensional mapping system showed continuous low potential in the ablation site, and pulmonary vein isolation (PVI) was achieved in all four PV of the patients. There were no recurrences, PV stenosis, or other serious adverse events during the 12 months follow-up. The results suggest that PFA using biphasic asymmetric waveforms for patients with AF is safe, durable, and effective and that a larger clinical trial could begin. Clinical Trial Registration: https://www.chictr.org.cn/, identifier, ChiCTR2100051894.

Study on the process of cardiomyocyte apoptosis after pulsed field ablation.

Background: The development of pulsed field ablation (PFA) as a new technique for pulmonary vein isolation (PVI) has been advancing rapidly in recent years. My team's previous work has shown the safety and long-term efficacy of bipolar asymmetric pulses in animal experiments. However, in ongoing clinical trials, we have observed that atrial fibrillation (AF) recurs in some patients after surgery, but the rhythm returns to normal without surgical intervention after seven days, and there is no recurrence in the follow-up.Based on this observation, we have proposed the hypothesis that myocardial cell apoptosis may play a role in AF recurrence after PFA. Our team has designed animal experiments to verify this hypothesis and further investigate the process of PFA-induced cardiomyocyte apoptosis. Methods: Pulse field ablation was performed on 15 dogs and the animals were dissected at various time points after the operation (immediately, 3 days, 7 days, 30 days, and 150 days). To obtain ablation voltage maps, electroanatomic mapping was performed before and after ablation and before dissection. The ablation area was also subjected to HE and TUNEL staining to analyze apoptosis and pathological results. Results: The edge area of the ablation in the pulmonary vein (PV) demonstrated continuous dynamic changes from 0 to 2 h after the operation and a slight expansion of the ablation range was observed in the long-term follow-up. Myocardial intima hyperplasia was observed from 0 to 7 days. Local apoptosis was detected from 0 to 2 h and massive, concentrated apoptosis was observed at 3 days. No recurrence of apoptosis was seen at 7 days, 30 days, and 150 days. Conclusions: The results of this study showed that after pulse field ablation (PFA), the central ablation area of the canine heart experienced immediate cardiomyocyte death. Meanwhile, cardiomyocytes in the edge ablation area underwent apoptosis, which began from 0 to 2 h post-operation and ended between 3 and 7 days. This process occurred simultaneously with intimal thickening.In the long-term follow-up group, there was no recovery of isolation and no recurrence of cardiomyocyte apoptosis, and no change was observed in the endomyocardial intima.

Preclinical Study of Biphasic Asymmetric Pulsed Field Ablation.

Pulsed field ablation (PFA) is a novel method of pulmonary venous isolation in atrial fibrillation ablation and is featured by tissue-selective ablation. Isolation is achieved via the application of high-voltage microsecond pulses that create irreversible perforations in cell membranes (i.e., electroporation). We proposed a new biphasic asymmetric pulse mode and verified the lesion persistence and safety of this mode for pulmonary vein ostia ablation in preclinical studies. We found that biphasic asymmetric pulses can effectively reduce muscle contractions and drop ablation threshold. In the electroanatomic mapping, the ablation site showed a continuous low potential area, and the atrium was not captured after 30 days of pacing. Pathological staining showed that cardiomyocytes in the ablation area were replaced by fibroblasts and there was no damage outside the ablation zone. Our results show that pulmonary venous isolation using the biphasic asymmetric discharge mode is safe, durable, effective, and causes no damage to other tissues.

Effects of the Tibetan medicine Byur dMar Nyer lNga Ril Bu on Alzheimer's disease in mice models.

ETHNOPHARMACOLOGICAL RELEVANCE: Byur dMar Nyer lNga Ril Bu (BdNlRB) is a classic Tibetan medicine prescription for treating " white vein disease". Alzheimer's disease (AD) is a chronic degenerative disease of the central nervous system, characterized by distinct "white vein disease". In the absence of effective drugs for AD, BdNlRB may be a possible treatment for AD. AIM OF THE STUDY: To verify the therapeutic effect and possible mechanism of the proved Tibetan medicine BdNlRB on Alzheimer's disease. MATERIALS AND METHODS: 60 APP/PS1 double transgenic AD mice (Mt) and 60 Aß1-40 protein-induced AD mice (Mi) were divided into 3 groups according to the dose of BdNlRB: BdNlRB-100, BdNlRB-200 and BdNlRB-400, with 100, 200 and 400 mg/kg*weight, respectively. The mice were administrated by gavage for 8 weeks. The cognitive ability of mice was detected by Morris Water Maze, the expression of Aß protein, p-tau and microglia was detected by immunofluorescent staining, the protein expression in the hippocampus was detected by proteomics, and the abundance of fecal intestinal flora was detected by 16S RNA. RESULTS: The learning ability and memory ability of Mi mice were significantly improved after BdNlRB administration. The learning ability of Mt mice was significantly improved, while the memory ability was not improved after BdNlRB administration. After the treatment with low and medium doses of BdNlRB, the expression of p-tau decreased significantly (the rate of decrease in BdNlRB-100 and BdNlRB-200 groups was 8.05% and 12.7%, respectively), and the number of microglia increased (39.3% and 31.6%, respectively). BdNlRB significantly affected the protein expression in the hippocampus of Mt mice. 382 proteins in different expression in all three groups mainly involved in amino acid synthesis, fatty acid degradation, glutamine metabolism, synaptic vesicular cycle and oxidative phosphorylation, PPAR signaling pathway and Fc gamma-mediated phagocytosis were activated. Meanwhile, the administration of BdNlRB can regulate the intestinal flora of Mt mice, which reduces the abundance of Muribaculum and uncultured bacteroidales bacterium, and improves the abundance of Ruminococcus-1 and Ruminiclostridium-9. CONCLUSION: The oral administration of BdNlRB significantly improved the cognitive ability of AD mice, and neuroinflammation and intestinal flora regulation were the possible mechanisms.

Study on Optimal Parameter and Target for Pulsed-Field Ablation of Atrial Fibrillation.

Pulsed-field ablation (PFA) had potential advantages in atrial fibrillation ablation, and we aim to confirm the optimal parameter and target of PFA for atrial fibrillation. Two ablation modes in vitro of single-cell system (ablation in electrode cup) and monolayer cell system (ablation in inserts with electrode tips) were established to perform PFA for myocardial cell H9C2 and smooth muscle cell A7r5. Ablation effect, calcium ion influx, the expression of Cx45, and surface morphological change were observed. Three Bama minipigs were used to verify the in vivo ablation effect of PFA. In monolayer cell system, H9C2 was significantly sensitive to PFA compared with A7r5, with shrinking of the whole monolayer. The ablation effect of bidirectional pulse was weaker than that of the two mono-polar pulses. Expressed Cx45 proteins were increased in H9C2 but decreased in A7r5 cells. Bidirectional PFA performed on Bama minipigs was able to effectively block electrical activity from the pulmonary vein to the atrium with week muscle contraction, not generating pulmonary vein stenosis. Bidirectional PFA was able to significantly ablate myocardial cells, maintain cell-cell connection, and reduce muscle contraction, which was a kind of optimized PFA strategy for atrial fibrillation.

Gut flora-targeted photobiomodulation therapy improves senile dementia in an Aß-induced Alzheimer's disease animal model.

BACKGROUND: Emerging evidence suggests that the gut microbiota plays an important role in the pathological progression of Alzheimer's disease (AD). Photobiomodulation (PBM) therapy is believed to have a positive regulatory effect on the imbalance of certain body functions, including inflammation, immunity, wound healing, nerve repair, and pain. Previous studies have found that the intestinal flora of patients with AD is in an unbalanced state. Therefore, we have proposed the use of gut flora-targeted PBM (gf-targeted PBM) as a method to improve AD in an Aß-induced AD mouse model. METHODS: PBM was performed on the abdomen of the mice at the wavelengths of 630 nm, 730 nm, and 850 nm at 100 J/cm2 for 8 weeks. Morris water maze test, immunofluorescence and proteomic of hippocampus, and intestinal flora detection of fecal were used to evaluate the treatment effects of gf-targeted PBM on AD rats. RESULTS: PBM at all three wavelengths (especially 630 nm and 730 nm) significantly improved learning retention as measured by the Morris water maze. In addition, we found reduced amyloidosis and tau phosphorylation in the hippocampus by immunofluorescence in AD mice. By using a quantitative proteomic analysis of the hippocampus, we found that gf-targeted PBM significantly altered the expression levels of 509 proteins (the same differentially expressed proteins in all three wavelengths of PBM), which involved the pathways of hormone synthesis, phagocytosis, and metabolism. The 16 s rRNA gene sequencing of fecal contents showed that PBM significantly altered the diversity and abundance of intestinal flora. Specifically, PBM treatment reversed the typical increase of Helicobacter and uncultured Bacteroidales and the decrease of Rikenella seen in AD mice. CONCLUSIONS: Our data indicate that gf-targeted PBM regulates the diversity of intestinal flora, which may improve damage caused by AD. Gf-targeted PBM has the potential to be a noninvasive microflora regulation method for AD patients.