ArticleAmerican journal of physiology. Heart and circulatory physiology2014
Beneficial effects of acute inhibition of the oxidative pentose phosphate pathway in the failing heart.
Article in American journal of physiology. Heart and circulatory physiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
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
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 34 citations in OpenAlex.
- Metabolic remodeling of substrate utilization during heart failure progression.Heart failure reviews · 2019Pooled it
- The Role of the Pentose Phosphate Pathway in Cardiovascular Diseases.Cardiovascular drugs and therapy · 2026Review
- NRF2 activation in the heart induces glucose metabolic reprogramming and reduces cardiac dysfunction via upregulation of the pentose phosphate pathway.Cardiovascular research · 2025Article
- Improving metabolic support during normothermicFrontiers in cardiovascular medicine · 2025Review
- Metabolomics in Atrial Fibrillation: Unlocking Novel Biomarkers and Pathways for Diagnosis, Prognosis, and Personalized Treatment.Journal of clinical medicine · 2024Review
- Review
- SGLT2 Inhibitors and How They Work Beyond the Glucosuric Effect. State of the Art.American journal of cardiovascular drugs : drugs, devices, and other interventions · 2024Review
- Metabolic adaptations in pressure overload hypertrophic heart.Heart failure reviews · 2024Review
- Integration of proteomic and metabolomic characterization in atrial fibrillation-induced heart failure.BMC genomics · 2022Article
- Metabolomic Profiling of End-Stage Heart Failure Secondary to Chronic Chagas Cardiomyopathy.International journal of molecular sciences · 2022Article
- Boosting the Discovery of Small Molecule Inhibitors of Glucose-6-Phosphate Dehydrogenase for the Treatment of Cancer, Infectious Diseases, and Inflammation.Journal of medicinal chemistry · 2022Review
- Effects of Bergamot Polyphenols on Mitochondrial Dysfunction and Sarcoplasmic Reticulum Stress in Diabetic Cardiomyopathy.Nutrients · 2021Review
- Targeting Adrenergic Receptors in Metabolic Therapies for Heart Failure.International journal of molecular sciences · 2021Review
- Evidence of a hormonal reshuffle in the cecal metabolome fingerprint of a strain of rats resistant to decompression sickness.Scientific reports · 2021Article
- Glucose Metabolism in Cardiac Hypertrophy and Heart Failure.Journal of the American Heart Association · 2019Review
- Article
- Metabolic Coordination of Physiological and Pathological Cardiac Remodeling.Circulation research · 2018Review
- Metabolic Response of the Immature Right Ventricle to Acute Pressure Overloading.Journal of the American Heart Association · 2018Article
- Glucose-6-phosphate dehydrogenase inhibition attenuates acute lung injury through reduction in NADPH oxidase-derived reactive oxygen species.Clinical and experimental immunology · 2018Article
- Pyridine Dinucleotides from Molecules to Man.Antioxidants & redox signaling · 2018Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 6 institutions in 3 countries.
Funding
Abstract
In vitro studies suggested that glucose metabolism through the oxidative pentose phosphate pathway (oxPPP) can paradoxically feed superoxide-generating enzymes in failing hearts. We therefore tested the hypothesis that acute inhibition of the oxPPP reduces oxidative stress and enhances function and metabolism of the failing heart, in vivo. In 10 chronically instrumented dogs, congestive heart failure (HF) was induced by high-frequency cardiac pacing. Myocardial glucose consumption was enhanced by raising arterial glycemia to levels mimicking postprandial peaks, before and after intravenous administration of the oxPPP inhibitor 6-aminonicotinamide (80 mg/kg). Myocardial energy substrate metabolism was measured with radiolabeled glucose and oleic acid, and cardiac 8-isoprostane output was used as an index of oxidative stress. A group of five chronically instrumented, normal dogs served as control. In HF, raising glycemic levels from ∼ 80 to ∼ 170 mg/dL increased cardiac isoprostane output by approximately twofold, whereas oxPPP inhibition normalized oxidative stress and enhanced cardiac oxygen consumption, glucose oxidation, and stroke work. In normal hearts glucose infusion did not induce significant changes in cardiac oxidative stress. Myocardial tissue concentration of 6P-gluconate, an intermediate metabolite of the oxPPP, was significantly reduced by ∼ 50% in treated versus nontreated failing hearts, supporting the inhibitory effect of 6-aminonicotinamide. Our study indicates an important contribution of the oxPPP activity to cardiac oxidative stress in HF, which is particularly pronounced during common physiological changes such as postprandial glycemic peaks.
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.