Resuscitation Outcomes Consortium (ROC) Amiodarone, Lidocaine or Neither for Out-Of-Hospital Cardiac Arrest Due to Ventricular Fibrillation or Ventricular Tachycardia (ALPS)(ROC-ALPS-BioLINCC)
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PROVIDER: PRJNA1163441 | ENA |
REPOSITORIES: ENA
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Project description:Resuscitation Outcomes Consortium (ROC) Amiodarone, Lidocaine or Neither for Out-Of-Hospital Cardiac Arrest Due to Ventricular Fibrillation or Ventricular Tachycardia (ALPS)(ROC-ALPS-BioLINCC)
| PRJNA1163442 | ENA
Project description:BackgroundDespite their wide use, whether antiarrhythmic drugs improve survival after out-of-hospital cardiac arrest (OHCA) is not known. The ROC-ALPS is evaluating the effectiveness of these drugs for OHCA due to shock-refractory ventricular fibrillation or pulseless ventricular tachycardia (VF/VT).MethodsALPS will randomize 3,000 adults across North America with nontraumatic OHCA, persistent or recurring VF/VT after ≥1 shock, and established vascular access to receive up to 450 mg amiodarone, 180 mg lidocaine, or placebo in the field using a double-blind protocol, along with standard resuscitation measures. The designated target population is all eligible randomized recipients of any dose of ALPS drug whose initial OHCA rhythm was VF/VT. A safety analysis includes all randomized patients regardless of their eligibility, initial arrhythmia, or actual receipt of ALPS drug. The primary outcome of ALPS is survival to hospital discharge; a secondary outcome is functional survival at discharge assessed as a modified Rankin Scale score ≤3.ResultsThe principal aim of ALPS is to determine if survival is improved by amiodarone compared with placebo; secondary aim is to determine if survival is improved by lidocaine vs placebo and/or by amiodarone vs lidocaine. Prioritizing comparisons in this manner acknowledges where differences in outcome are most expected based on existing knowledge. Each aim also represents a clinically relevant comparison between treatments that is worth investigating.ConclusionsResults from ALPS will provide important information about the choice and value of antiarrhythmic therapies for VF/VT arrest with direct implications for resuscitation guidelines and clinical practice.
| S-EPMC4014351 | biostudies-literature
Project description:This study aimed to explore the possible mechanism of lidocaine-induced neurotoxicity. A total of 40 rats were randomly assigned to 4 groups (n = 10 per group): control group; sham group, received only intrathecal catheter insertion; saline group, received an intrathecal injection of saline; and lidocaine group, received an intrathecal injection of 10% lidocaine. Neurobehavioral tests were performed on rats in each group before injection and 1, 2, 3, and 4 days after the intrathecal injection. On the fourth day, after completing neurobehavioral tests, the spinal cords of all rats from L2 to L6 were removed and immediately stored in liquid nitrogen. In the control and lidocaine groups, parts of the spinal cord tissues of three rats were selected for gene microarray analysis.Based on the results of the gene chip analysis,Five rats in each group underwent real-time quantitative polymerase chain reaction (PCR) and five Western blot analysis to verify Differentially expressed genes at the mRNA transcription and protein levels. The aim of gene chip analysis is to screen potential genes involved in lidocaine-induced neurotoxicity.
2019-09-05 | GSE136833 | GEO
Project description:BackgroundOut-of-hospital cardiac arrest (OHCA) commonly presents with nonshockable rhythms (asystole and pulseless electric activity). It is unknown whether antiarrhythmic drugs are safe and effective when nonshockable rhythms evolve to shockable rhythms (ventricular fibrillation/pulseless ventricular tachycardia [VF/VT]) during resuscitation.MethodsAdults with nontraumatic OHCA, vascular access, and VF/VT anytime after ≥1 shock(s) were prospectively randomized, double-blind, to receive amiodarone, lidocaine, or placebo by paramedics. Patients presenting with initial shock-refractory VF/VT were previously reported. The current study was a prespecified analysis in a separate cohort that initially presented with nonshockable OHCA and was randomized on subsequently developing shock-refractory VF/VT. The primary outcome was survival to hospital discharge. Secondary outcomes included discharge functional status and adverse drug-related effects.ResultsOf 37 889 patients with OHCA, 3026 with initial VF/VT and 1063 with initial nonshockable-turned-shockable rhythms were treatment-eligible, were randomized, and received their assigned drug. Baseline characteristics among patients with nonshockable-turned-shockable rhythms were balanced across treatment arms, except that recipients of a placebo included fewer men and were less likely to receive bystander cardiopulmonary resuscitation. Active-drug recipients in this cohort required fewer shocks, supplemental doses of their assigned drug, and ancillary antiarrhythmic drugs than recipients of a placebo (P<0.05). In all, 16 (4.1%) amiodarone, 11 (3.1%) lidocaine, and 6 (1.9%) placebo-treated patients survived to hospital discharge (P=0.24). No significant interaction between treatment assignment and discharge survival occurred with the initiating OHCA rhythm (asystole, pulseless electric activity, or VF/VT). Survival in each of these categories was consistently higher with active drugs, although the trends were not statistically significant. Adjusted absolute differences (95% confidence interval) in survival from nonshockable-turned-shockable arrhythmias with amiodarone versus placebo were 2.3% (-0.3, 4.8), P=0.08, and for lidocaine versus placebo 1.2% (-1.1, 3.6), P=0.30. More than 50% of these survivors were functionally independent or required minimal assistance. Drug-related adverse effects were infrequent.ConclusionsOutcome from nonshockable-turned-shockable OHCA is poor but not invariably fatal. Although not statistically significant, point estimates for survival were greater after amiodarone or lidocaine than placebo, without increased risk of adverse effects or disability and consistent with previously observed favorable trends from treatment of initial shock-refractory VF/VT with these drugs. Together the findings may signal a clinical benefit that invites further investigation.Clinical trial registrationURL: https://www.clinicaltrials.gov. Unique identifier: NCT01401647.
| S-EPMC5705566 | biostudies-literature
Project description:In order to identify microRNAs (miRNAs) that were involved in the effects of anesthetics on breast cancer cells, Illumina next generation miRNA sequencing was performed to search for any differentially expressed miRNAs in responding to lidocaine and bupivacaine treatments in MCF7 breast cancer cells. The filtering criteria for identifying differentially expressed miRNAs in the lidocaine and bupivacaine groups were fold change ≥ 2.0X and P-value ≤ 0.05. In total, there were 1,228 significantly upregulated miRNAs in lidocaine group and 133 miRNAs in bupivacaine group. On the contrary, there were 25 significantly downregulated miRNAs in lidocaine group and 36 miRNAs in bupivacaine group.
2022-01-13 | GSE171282 | GEO
Project description:(1) Background: Catheter ablation (CA) is an accepted treatment option for drug-refractory ventricular tachycardia (VT) in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC). This study investigates the effect of amiodarone on ablation outcomes in ARVC. (2) Methods: The study enrolled patients with ARVC undergoing CA of sustained VT. In all patients, substrate modification was performed to achieve non-inducible VT. The patients were categorized into two groups according to whether they had used amiodarone before CA. Baseline and electrophysiological characteristics, substrate, and outcomes were compared. (3) Results: A total of 72 ARVC patients were studied, including 29 (40.3%) "off" amiodarone and 43 (56.7%) "on" amiodarone. The scar area was similar between the two groups. Patients "off" amiodarone had smaller endocardial and epicardial areas with abnormal electrograms. Twenty of 43 patients (47.5%) "on" amiodarone discontinued it within 3 months after CA. During a mean follow-up period of 43.2 ± 29.5 months, higher VT recurrence was observed in patients "on" amiodarone. Patients "on" amiodarone who discontinued amiodarone after CA had a lower recurrence than those without. (4) Conclusions: Patients with ARVC "on" amiodarone before CA had distinct substrate characteristics and worse ablation outcomes than patients "off" amiodarone, especially in those who had used amiodarone continuously.
| S-EPMC9787968 | biostudies-literature
Project description:We conducted RNA-sequencing of lidocaine hydrochloride in treating rat dorsal root ganglion neurons to detect lidocaine’s effect of transcriptome profiling changes compared with control.
2019-11-09 | GSE140162 | GEO
Project description:Amiodarone (AMD) and nifekalant (NIF) are used in the treatment of ventricular fibrillation or tachycardia; however, only few studies have been conducted on their efficacies. Therefore, a meta-analysis was conducted. Relevant sources were identified from PubMed, Cochrane Central Register of Controlled Trials, and Igaku Chuo Zasshi. The outcomes were short-term and long-term survival in patients with shock-resistant ventricular fibrillation /pulseless ventricular tachycardia. Thirty-three studies were analysed. The results showed that, compared to the control treatment, AMD did not improve short-term survival (odds ratio (OR): 1.25, 95% confidence interval (CI): 0.91-1.71) or long-term survival (OR: 1.00, 95% CI: 0.63-1.57). However, compared to the control treatment, NIF significantly improved short-term survival (OR: 3.23, 95% CI: 2.21-4.72) and long-term survival (OR: 1.88, 95% CI: 1.36-2.59). No significant difference was observed in short-term survival (OR: 0.85, 95% CI: 0.63-1.15) or long-term survival (OR: 1.25, 95% CI: 0.67-2.31) between AMD- and NIF-treated patients. The results suggest that NIF is beneficial for short-term and long-term survival in shock-resistant ventricular fibrillation/pulseless ventricular tachycardia; however, the efficacy of AMD in either outcome is not clear.
| S-EPMC5627292 | biostudies-literature
Project description:To investigate changes in hippocampal genes mice after lidocaine injections
2024-07-01 | GSE270941 | GEO
Project description:Autophagy plays important roles in malignant pathogenesis and drug resistance. We used medicinal chemistry approaches to generate a series of novel agents that inhibit autophagic degradation. ROC-325 was selected as a lead compound for further evaluation. Comprehensive in vitro and in vivo studies were conducted to evaluate the selectivity, tolerability, and efficacy of ROC-325 in preclinical models of renal cell carcinoma (RCC). ROC-325 exhibited superior in vitro anticancer effects than the existing autophagy inhibitor hydroxychloroquine in 12 different tumor models with diverse genetic backgrounds. Focused studies of the mechanism of action and efficacy of ROC-325 in RCC cells showed that drug treatment induced hallmark characteristics of autophagy inhibition including accumulation of autophagosomes with undegraded cargo, lysosomal deacidification, p62 stabilization, and disruption of autophagic flux. Subsequent experiments showed that ROC-325 antagonized RCC growth and survival in an ATG5/7-dependent manner, induced apoptosis, and exhibited favorable selectivity. Oral administration of ROC-325 to mice bearing 786-0 RCC xenografts was well tolerated, significantly more effective at inhibiting tumor progression than HCQ, and inhibited autophagy in vivo. We used microarrays to determine gene expression changes following 24 h treatment with ROC-325 in RCC cell lines and identified differentially expressed genes.
2018-02-16 | GSE89766 | GEO