ArticleHeart rhythm2006
Blinded validation of the isolated arterially perfused rabbit ventricular wedge in preclinical assessment of drug-induced proarrhythmias.
Article in Heart rhythm, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
46 citing papers in PubMed, 124 citations in OpenAlex.
- Evaluation of the QT effect of a combination of piperaquine and a novel anti-malarial drug candidate OZ439, for the treatment of uncomplicated malaria.British journal of clinical pharmacology · 2015Trial
- Role of mixed ion channel effects in the cardiovascular safety assessment of the novel anti-MRSA fluoroquinolone JNJ-Q2.British journal of pharmacology · 2012Trial
- Overview and Prospects of the Clinical Application of Oliceridine.Drug design, development and therapy · 2025Review
- Mechanisms of Chemical Atrial Defibrillation by Flecainide and Ibutilide.JACC. Clinical electrophysiology · 2024Article
- Effect of Flecainide and Ibutilide Alone and in Combination to Terminate and Prevent Recurrence of Atrial Fibrillation.Circulation. Arrhythmia and electrophysiology · 2024Article
- The Potential Mechanisms behind Loperamide-Induced Cardiac Arrhythmias Associated with Human Abuse and Extreme Overdose.Biomolecules · 2023Article
- Cross clinical-experimental-computational qualification ofFrontiers in toxicology · 2022Article
- Intracellular uptake of agents that block the hERG channel can confound the assessment of QT interval prolongation and arrhythmic risk.Heart rhythm · 2021Article
- Comprehensive in vitro pro-arrhythmic assays demonstrate that omecamtiv mecarbil has low pro-arrhythmic risk.Clinical and translational science · 2021Article
- Evaluation of Index of Cardio-Electrophysiological Balance in Patients With Atrial Fibrillation on Antiarrhythmic-Drug Therapy.Cardiology research · 2021Article
- Integrated Isogenic Human Induced Pluripotent Stem Cell-Based Liver and Heart Microphysiological Systems Predict Unsafe Drug-Drug Interaction.Frontiers in pharmacology · 2021Article
- Novel method for action potential measurements from intact cardiac monolayers with multiwell microelectrode array technology.Scientific reports · 2019Article
- Identification of GSK3186899/DDD853651 as a Preclinical Development Candidate for the Treatment of Visceral Leishmaniasis.Journal of medicinal chemistry · 2019Article
- Identification of Quinoline-Based RIP2 Kinase Inhibitors with an Improved Therapeutic Index to the hERG Ion Channel.ACS medicinal chemistry letters · 2018Article
- Therapeutic effects of a taurine-magnesium coordination compound on experimental models of type 2 short QT syndrome.Acta pharmacologica Sinica · 2018Article
- Synergistic Effect of Dofetilide and Mexiletine on Prevention of Atrial Fibrillation.Journal of the American Heart Association · 2017Article
- HumanFrontiers in physiology · 2017Article
- Evolution of strategies to improve preclinical cardiac safety testing.Nature reviews. Drug discovery · 2016Review
- Protective Effects of Carvedilol and Vitamin C against Azithromycin-Induced Cardiotoxicity in Rats via Decreasing ROS, IL1-β, and TNF-α Production and Inhibiting NF-κB and Caspase-3 Expression.Oxidative medicine and cellular longevity · 2016Article
- Effects of neferine on Kv4.3 channels expressed in HEK293 cells and ex vivo electrophysiology of rabbit hearts.Acta pharmacologica Sinica · 2015Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
backgroundThe development of preclinical models with high predictive value for the identification of drugs with a proclivity to induce Torsade de Pointes (TdP) in the clinic has long been a pressing goal of academia, industry and regulatory agencies alike. The present study provides a blinded appraisal of drugs, in an isolated arterially-perfused rabbit ventricular wedge preparation, with and without the potential to produce TdP. METHODS AND
resultsThirteen compounds were tested for their potential for TdP using the rabbit left ventricular wedges. All investigators were blinded to the names, concentrations and molecular weights of the drugs. The compounds were prepared by the study sponsor and sent to the investigator as 4 sets of 13 stock solutions with the order within each set being assigned by a random number generator. Each compound was scored semi-quantitatively for its relative potential for TdP based on its effect on ventricular repolarization measured as QT interval, dispersion of repolarization measured as T(p-e)/QT ratio and early afterdepolarizations. Disclosure of the names and concentrations after completion of the study revealed that all compounds known to be free of TdP risk received a score of less or equal to 0.25, whereas those with known TdP risk received a score ranging from 1.00 to 7.25 at concentrations less than 100X their free therapeutic plasma C(max).
conclusionsOur study provides a blinded evaluation of the isolated arterially-perfused rabbit wedge preparation demonstrating both a high sensitivity and specificity in the assessment of 13 agents with varying propensity for causing TdP.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.