ArticleJournal of the American College of Cardiology2015
The Classically Cardioprotective Agent Diazoxide Elicits Arrhythmias in Type 2 Diabetes Mellitus.
Article in Journal of the American College of Cardiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 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
13 citing papers in PubMed, 20 citations in OpenAlex.
- Mitochondrial network remodeling of the diabetic heart: implications to ischemia related cardiac dysfunction.Cardiovascular diabetology · 2024Review
- Quantitative Assessment of Mitochondrial Morphology and Electrophysiological Function in the Diabetic Heart.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Right predominant electrical remodeling in a pure model of pulmonary hypertension promotes reentrant arrhythmias.Heart rhythm · 2022Article
- Cardiomyocyte-Specific STIM1 (Stromal Interaction Molecule 1) Depletion in the Adult Heart Promotes the Development of Arrhythmogenic Discordant Alternans.Circulation. Arrhythmia and electrophysiology · 2019Article
- Intra-tracheal gene delivery of aerosolized SERCA2a to the lung suppresses ventricular arrhythmias in a model of pulmonary arterial hypertension.Journal of molecular and cellular cardiology · 2019Article
- Functional protection against cardiac diseases depends on ATP-sensitive potassium channels.Journal of cellular and molecular medicine · 2018Review
- The Mitochondrial Translocator Protein and the Emerging Link Between Oxidative Stress and Arrhythmias in the Diabetic Heart.Frontiers in physiology · 2018Review
- The Pattern of mRNA Expression Is Changed in Sinoatrial Node from Goto-Kakizaki Type 2 Diabetic Rat Heart.Journal of diabetes research · 2018Article
- Protein Phosphatase Inhibitor-1 Gene Therapy in a Swine Model of Nonischemic Heart Failure.Journal of the American College of Cardiology · 2017Article
- Oral treatment with a zinc complex of acetylsalicylic acid prevents diabetic cardiomyopathy in a rat model of type-2 diabetes: activation of the Akt pathway.Cardiovascular diabetology · 2016Article
- Molecular and Electrophysiological Mechanisms Underlying Cardiac Arrhythmogenesis in Diabetes Mellitus.Journal of diabetes research · 2016Review
- KATP Channels in the Cardiovascular System.Physiological reviews · 2016Review
- How Does Diazoxide Elicit Arrhythmias in Rats With Type 2 Diabetes?: Is This Effect Clinically Significant?Journal of the American College of Cardiology · 2015Article
Corrections and comments
- Commented on by
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
backgroundType 2 diabetes mellitus (T2DM) is associated with an enhanced propensity for ventricular tachyarrhythmias (VTs) under conditions of metabolic demand. Activation of mitochondrial adenosine triphosphate-sensitive potassium (KATP) channels by low-dose diazoxide (DZX) improves hypoglycemia-related complications, metabolic function, and triglyceride and free fatty acid levels and reverses weight gain in T2DM.
objectivesIn this study, we hypothesized that DZX prevents ischemia-mediated arrhythmias in T2DM via its putative cardioprotective and antidiabetic property.
methodsZucker obese diabetic fatty (ZO) rats (n = 43) with T2DM were studied. Controls consisted of Zucker lean (ZL; n = 13) and normal Sprague-Dawley (SprD; n = 30) rats. High-resolution optical action potential mapping was performed before and during challenge with no-flow ischemia for 12 min.
resultsElectrophysiological properties were relatively stable in T2DM hearts at baseline. In contrast, ischemia uncovered major differences between groups, because action potential duration (APD) in T2DM failed to undergo progressive adaptation to ischemic challenge. DZX promoted the incidence of arrhythmias, because all DZX-treated T2DM hearts exhibited ischemia-induced VTs that persisted on reperfusion. In contrast, untreated T2DM and controls did not exhibit VT during ischemia. Unlike DZX, pinacidil promoted ischemia-mediated arrhythmias in both control and T2DM hearts. Rapid and spatially heterogeneous shortening of APD preceded the onset of arrhythmias in T2DM. DZX-mediated proarrhythmia in T2DM was not related to changes in the messenger ribonucleic acid expression of Kir6.1, Kir6.2, SUR1A, SUR1B, SUR2A, SUR2B, or ROMK (renal outer medullary potassium channel).
conclusionsIschemia uncovers a paradoxical resistance of T2DM hearts to APD adaptation. DZX reverses this property, resulting in rapid and heterogeneous APD shortening. This promotes reentrant VT during ischemia. DZX should be avoided in diabetic patients at risk of ischemic events.
Indexed as
Identifiers
What OpenQuestion holds
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.