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.

Novel irreversible electroporation ablation (Nano-knife) versus radiofrequency ablation for the treatment of solid liver tumors: a comparative, randomized, multicenter clinical study.

Irreversible electroporation (IRE) is a soft tissue ablation technique that uses short electrical fields which induce the death of target cells. To evaluate the safety and efficacy of an IRE-based device compared to regular radiofrequency ablation (RFA) of solid liver tumors, in this multicenter, randomized, parallel-arm, non-inferiority study, 152 patients with malignant liver tumors were randomized into IRE (n = 78) and RFA (n = 74) groups. The primary endpoint was the success rate of tumor ablation; the secondary endpoints included the tumor ablation time, complications, tumor recurrence rates and treatment-related adverse events (TRAE). The success rate of tumor ablation using IRE was 94.9% and was non-inferior to the RFA group (96.0%) (P = 0.761). For the secondary endpoints, the average ablation time was 34.29 ± 30.38 min for the IRE group, which was significantly longer than for the RFA group (19.91 ± 16.08 min) (P < 0.001). The incidences of postoperative complications after 1 week (P = 1.000), 1 month (P = 0.610) and 3 months (P = 0.490) were not significantly different between the 2 groups. The recurrence rates of liver tumor at 1, 3 and 6 months after ablation were 0 (0.0%), 10 (13.9%) and 10 (13.3%) in the IRE group and 2.9%, 7.3% and 19.7% in the RFA control group (all P > 0.05), respectively. For safety assessments, 51 patients experienced 191 AEs (65.4%) in the IRE group, which was not different from the RFA group (73.0%, 54/184) (P = 0.646). In 7 IRE patients, 8 TRAEs (7.9%) occurred, the most common being edema of the limbs (mild grade) and fever (severe grade), while no TRAEs occurred in the RFA group. This study proved that the excellent safety and efficacy of IRE was non-inferior to the regular radiofrequency device in ablation performance for the treatment of solid liver tumors. Clinical trial registration: Chinese Clinical Trial Registry: ChiCTR1800017516.

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.

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.

High-voltage pulsed electric field plus photodynamic therapy kills breast cancer cells by triggering apoptosis.

This study evaluated the effects and mechanism of action of combining irreversible electroporation (IRE) and photodynamic therapy (PDT) in breast cancer cells in vitro and in vivo. Jin's formula was used to assess killing efficacy of different IRE+PDT dosing combinations in breast cancer MCF-7 cells. Flow cytometry, high-content imaging, and confocal laser scanning microscopy were used to detect apoptosis. qRT-PCR and western blotting were used to evaluate expression of apoptosis-related genes and proteins. IRE+PDT combination therapy was administered to BALB/C mice with breast cancer tumors in vivo; tumor size was used to assess treatment efficacy. Killing mechanisms were examined using transmission electron microscopy and immunohistochemistry. We found that IRE+PDT combination therapy produced significant synergistic killing effects in breast cancer cells (highest Jin q value of 1.32). Early apoptosis rates were significantly higher in the IRE+PDT group (16.0%) than in IRE-alone (7.6%) and PDT-alone (4.6%) groups (P<0.05). qRT-PCR showed higher Caspase-1, -3, -5, -6, -7, -8, and -9 and TNFRSF1A expression with IRE+PDT than with control. Western blots showed increased cleaved Caspase-3, -7, and -9, and PARP levels in the IRE+PDT group. In vivo tumor suppression rate for IRE (1200 V)+PDT (10 mg/kg) was 68.3%. Combination therapy produced the most obvious apoptosis effects. Compared with controls, the IRE+PDT group exhibited lower new blood vessel (VEGF, CD31), metastasis (TGF-ß), and cell proliferation (Ki-67) indicators and higher inflammation indicator (TNF-α) 1 day post-treatment. Thus, combining IRE and PDT enhanced their anti-tumor effects in breast cancer, and apoptosis played a key role in this process.

Inhibition of miR-630 enhances the cell resistance to radiation by directly targeting CDC14A in human glioma.

Radio-resistance becomes a large obstacle for effective cancer treatment. MicroRNAs (miRNAs) play important roles in response to radiation. However, the underlying mechanism of miR-630 on the radio-resistance of human glioma is less elucidated. In this study, we found that miR-630 was downregulated in glioma cell lines after radiation. MiR-630 inhibition enhanced the survival fraction, cell number in S stage and colony formation ability in glioma cells after radiation, while miR-630 overexpression resulted in inverse effects. By detecting the molecular mechanism of miR-630, we validated that CDC14A was a direct target of miR-630 and miR-630 suppressed CDC14A protein level. CDC14A overexpression can attenuate the inhibitory roles of miR-630 in survival fraction and cell proliferation. Finally, in vivo study demonstrated that miR-630 inhibition increased the volumes of xenografts bearing with glioma cells after radiation. In conclusion, our data indicate that anti-miR-630 enhances the radio-resistance of human glioma cells by targeting CDC14A, implying that miR-630 may act as a novel therapeutic target for enhancing the radiation efficiency on glioma patients.

Antiinflammatory effect of low-level laser therapy on Staphylococcus epidermidis endophthalmitis in rabbits.

A rabbit model of endophthalmitis was established to evaluate the antiinflammatory effect of low-level laser therapy (LLLT) as an adjunct to treatment for Staphylococcus epidermidis endophthalmitis. Rabbits were randomly divided into three groups to receive intravitreal injections into their left eye: group A received 0.5 mg vancomycin (100 µl), group B received 0.5 mg vancomycin + 0.2 mg dexamethasone (100 µl), and group C received 0.5 mg vancomycin (100 µl) and continuous wave semiconductor laser irradiation (10 mW, λ = 632 nm) focused on the pupil. Slit lamp examination and B-mode ultrasonography were conducted to evaluate the symptoms of endophthalmitis. Polymorphonuclear cells and tumour necrosis factor alpha (TNF-α) in aqueous fluid were measured at 0 h, and 1, 2, 3, 7 and 15 days. A histology test was conducted at 15 days. B-mode ultrasonography and histology revealed that groups B and C had less inflammation than group A at 15 days. Groups B and C had fewer polymorphonuclear cells and lower levels of TNF-α in aqueous fluid than group A at 2, 3 and 7 days (P < 0.05). There was no significant difference between groups B and C (P > 0.05). There was no significant difference between groups A, B and C at 15 days (P > 0.05). As an adjunct to vancomycin therapy to treat S. epidermidis endophthalmitis, LLLT has an antiinflammatory effect similar to that of dexamethasone.

Photoinactivation of cell-free human immunodeficiency virus by hematoporphyrin monomethyl ether.

Human immunodeficiency virus (HIV) particles that remain in the blood of patients are frequently ignored as targets for AIDS treatment. We therefore investigated the use of photodynamic therapy (PDT) with hematoporphyrin monomethyl ether (HMME) as a means of inactivating cell-free HIV in vitro. Virus particles including HIV-1(IIIB), resistant HIV-1 variants, HIV-1 clinical variants, and HIV-2 variants were incubated with HMME for 40 min, followed by irradiation with a 630-nm semiconductor laser at an energy density of 0.3 J/cm(2). The antiviral effects were evaluated by counting syncytium formation or measuring p24 antigen expression levels in supernatants by enzyme-linked immunosorbent assay. The relationships between photoinactivation and HMME concentrations, energy density, power density and antioxidants (NaN(3) and D: -mannitol) were also assessed using the above methods. All the tested virus particles were completely responsive to HMME-PDT. HMME concentration and energy density were positively correlated with photoinactivation of HIV, while power density was negatively correlated. Both sodium azide and D: -mannitol weakened the inhibitory effect of PDT on virus-induced membrane fusion, with D: -mannitol having a stronger effect. HMME-PDT can inactivate HIV particles, and may therefore represent a promising treatment for AIDS patients.

Effect of CO(2) laser sclerectomy with iridectomy on ocular hypertension in rabbits.

AIM: To evaluate the efficiency and safety of an optimized CO(2) Laser glaucoma surgery system for laser sclerectomy with iridectomy. METHODS: Rabbit trials were performed to evaluate the efficiency and safety. RESULTS: IOP was significantly decreased in laser group compared with trabeculectomy group(P<0.05) from 7(th) postoperative day to 60(th) day. Compared with trabeculectomy group, histopathology studies confirmed fewer complications and better effects were found in laser group. CONCLUSION: CO(2) laser sclerectomy with iridectomy is effective and safe in terms of IOP lowering.