Trial reportEuropean journal of nuclear medicine and molecular imaging2005
Tetrahydrobiopterin restores impaired coronary microvascular dysfunction in hypercholesterolaemia.
Trial report in European journal of nuclear medicine and molecular imaging, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 18 papers.
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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.
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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.
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Who cites it
18 citing papers in PubMed, 37 citations in OpenAlex.
- Effects of Sapropterin on Portal and Systemic Hemodynamics in Patients With Cirrhosis and Portal Hypertension: A Bicentric Double-Blind Placebo-Controlled Study.The American journal of gastroenterology · 2015Trial
- Physical Exercise Protects Against Endothelial Dysfunction in Cardiovascular and Metabolic Diseases.Journal of cardiovascular translational research · 2022Review
- Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their RegulationPhysiological reviews · 2019Review
- Hypercholesterolemia-Induced Loss of Flow-Induced Vasodilation and Lesion Formation in Apolipoprotein E-Deficient Mice Critically Depend on Inwardly Rectifying KJournal of the American Heart Association · 2018Article
- Roles of NADPH oxidase and mitochondria in flow-induced vasodilation of human adipose arterioles: ROS-induced ROS release in coronary artery disease.Microcirculation (New York, N.Y. : 1994) · 2017Article
- Mildly compromised tetrahydrobiopterin cofactor biosynthesis due to Pts variants leads to unusual body fat distribution and abdominal obesity in mice.Journal of inherited metabolic disease · 2016Article
- Validating the GTP-cyclohydrolase 1-feedback regulatory complex as a therapeutic target using biophysical and in vivo approaches.British journal of pharmacology · 2015Article
- Role for Tetrahydrobiopterin in the Fetoplacental Endothelial Dysfunction in Maternal Supraphysiological Hypercholesterolemia.Oxidative medicine and cellular longevity · 2015Review
- Tetrahydrobiopterin in cardiovascular health and disease.Antioxidants & redox signaling · 2014Review
- Tetrahydrobiopterin improves endothelial function in cardiovascular disease: a systematic review.Evidence-based complementary and alternative medicine : eCAM · 2014Review
- Synthesis and recycling of tetrahydrobiopterin in endothelial function and vascular disease.Nitric oxide : biology and chemistry · 2011Review
- Risk prediction in cardiovascular disease: the prognostic significance of endothelial dysfunction.The Canadian journal of cardiology · 2009Review
- Vascular protection by tetrahydrobiopterin: progress and therapeutic prospects.Trends in pharmacological sciences · 2009Review
- Assessment of intra- and interobserver reproducibility of rest and cold pressor test-stimulated myocardial blood flow with (13)N-ammonia and PET.European journal of nuclear medicine and molecular imaging · 2007Article
- Role of PET in the evaluation and understanding of coronary physiology.Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology · 2007Review
- PET-measured heterogeneity in longitudinal myocardial blood flow in response to sympathetic and pharmacologic stress as a non-invasive probe of epicardial vasomotor dysfunction.European journal of nuclear medicine and molecular imaging · 2006Article
- Benefits of exercise training on coronary blood flow in coronary artery disease patients.Progress in cardiovascular diseasesReview
- Assessment of myocardial perfusion by dynamic O-15-labeled water PET imaging: validation of a new fast factor analysis.Journal of nuclear cardiology : official publication of the American Society of Nuclear CardiologyArticle
Corrections and comments
- Erratum issued
Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
purposeTetrahydrobiopterin (BH4) is an essential co-factor for the synthesis of nitric oxide (NO), and BH4 deficiency may cause impaired NO synthase (NOS) activity. We studied whether BH4 deficiency contributes to the coronary microcirculatory dysfunction observed in patients with hypercholesterolaemia.
methodsMyocardial blood flow (MBF; ml min(-1) g(-1)) was measured at rest, during adenosine-induced (140 microg kg(-1) min(-1) over 7 min) hyperaemia (mainly non-endothelium dependent) and immediately after supine bicycle exercise (endothelium-dependent) stress in ten healthy volunteers and in nine hypercholesterolaemic subjects using 15O-labelled water and positron emission tomography. Measurements were repeated 60 min later, after intravenous infusion of BH4 (10 mg kg(-1) body weight over 30 min). Adenosine-induced hyperaemic MBF is considered to represent (near) maximal flow. Flow reserve utilisation was calculated as the ratio of exercise-induced to adenosine-induced hyperaemic MBF and expressed as percent to indicate how much of the maximal (adenosine-induced) hyperaemia can be achieved by bicycle stress.
resultsBH4 increased exercise-induced hyperaemia in controls (2.96+/-0.58 vs 3.41+/-0.73 ml min(-1) g(-1), p<0.05) and hypercholesterolaemic subjects (2.47+/-0.78 vs 2.70+/-0.72 ml min(-1) g(-1), p<0.01) but had no influence on MBF at rest or during adenosine-induced hyperaemia in controls (4.52+/-1.10 vs 4.85+/-0.45 ml min(-1) g(-1), p=NS) or hypercholesterolaemic subjects (4.86+/-1.18 vs 4.53+/-0.93 ml min(-1) g(-1), p=NS). Flow reserve utilisation remained unchanged in controls (70+/-17% vs 71+/-19%, p=NS) but increased significantly in hypercholesterolaemic subjects (53+/-15% vs 66+/-14%, p<0.05).
conclusionBH4 restores flow reserve utilisation of the coronary microcirculation in hypercholesterolaemic subjects, suggesting that BH4 deficiency may contribute to coronary microcirculatory dysfunction in hypercholesterolaemia.
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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.