ArticlePharmacological research2011
Ranolazine reduces Ca2+ overload and oxidative stress and improves mitochondrial integrity to protect against ischemia reperfusion injury in isolated hearts.
Article in Pharmacological research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 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
60 citing papers in PubMed, 110 citations in OpenAlex.
- Late sodium channel blockade improves angina and myocardial perfusion in patients with severe coronary microvascular dysfunction: Women's Ischemia Syndrome Evaluation-Coronary Vascular Dysfunction ancillary study.International journal of cardiology · 2019Trial
- Protective Effects of Ranolazine in a Rat Model of Ovarian Ischemia/Reperfusion Injury.International journal of molecular sciences · 2026Article
- Review
- Effects of Ranolazine on Vascular Adrenergic Receptors in Rabbit Aorta.International journal of medical sciences · 2026Article
- Ranolazine neuroprotection against middle cerebral artery occlusion/reperfusion ischemic injury via modulation of brain-derived neurotrophic factor and brain mitochondrial tu translation elongation factor (TUFM).Metabolic brain disease · 2025Article
- AEOL-induced NRF2 activation and DWORF overexpression mitigate myocardial I/R injury.Molecular medicine (Cambridge, Mass.) · 2025Article
- Cerebral Small Vessel Disease: Therapeutic Approaches Targeting Neuroinflammation, Oxidative Stress, and Endothelial Dysfunction.Current issues in molecular biology · 2025Review
- Differential CaFrontiers in synaptic neuroscience · 2025Article
- Effects of GS-967, GS-6615 and ranolazine on the responses of the rabbit aorta to adrenergic nerve stimulation.Frontiers in physiology · 2025Article
- Mitochondrial dysfunction is a key link involved in the pathogenesis of sick sinus syndrome: a review.Frontiers in cardiovascular medicine · 2024Review
- Improvement of Vascular Insulin Sensitivity by Ranolazine.International journal of molecular sciences · 2023Article
- Administration of metformin rescues age-related vulnerability to ischemic insults through mitochondrial energy metabolism.Biochemical and biophysical research communications · 2023Article
- Mitochondrial Dysfunction in Cardiac Diseases and Therapeutic Strategies.Biomedicines · 2023Review
- Calcium and Reactive Oxygen Species Signaling Interplays in Cardiac Physiology and Pathologies.Antioxidants (Basel, Switzerland) · 2023Review
- Facilitation of Insulin Effects by Ranolazine in Astrocytes in Primary Culture.International journal of molecular sciences · 2022Article
- CD137 Signal Mediates Cardiac Ischemia-Reperfusion Injury by Regulating the Necrosis of Cardiomyocytes.Journal of cardiovascular translational research · 2022Article
- Hypothermia Prevents Cardiac Dysfunction during Acute Ischemia Reperfusion by Maintaining Mitochondrial Bioenergetics and by Promoting Hexokinase II Binding to Mitochondria.Oxidative medicine and cellular longevity · 2022Article
- Verapamil Alleviates Myocardial Ischemia/Reperfusion Injury by Attenuating Oxidative Stress via Activation of SIRT1.Frontiers in pharmacology · 2022Article
- Ranolazine: An Old Drug with Emerging Potential; Lessons from Pre-Clinical and Clinical Investigations for Possible Repositioning.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Late sodium current and calcium homeostasis in arrhythmogenesis.Channels (Austin, Tex.) · 2021Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Ranolazine is a clinically approved drug for treating cardiac ventricular dysrhythmias and angina. Its mechanism(s) of protection is not clearly understood but evidence points to blocking the late Na+ current that arises during ischemia, blocking mitochondrial complex I activity, or modulating mitochondrial metabolism. Here we tested the effect of ranolazine treatment before ischemia at the mitochondrial level in intact isolated hearts and in mitochondria isolated from hearts at different times of reperfusion. Left ventricular (LV) pressure (LVP), coronary flow (CF), and O2 metabolism were measured in guinea pig isolated hearts perfused with Krebs-Ringer's solution; mitochondrial (m) superoxide (O2·-), Ca2+, NADH/FAD (redox state), and cytosolic (c) Ca2+ were assessed on-line in the LV free wall by fluorescence spectrophotometry. Ranolazine (5 μM), infused for 1 min just before 30 min of global ischemia, itself did not change O2·-, cCa2+, mCa2+ or redox state. During late ischemia and reperfusion (IR) O2·- emission and m[Ca2+] increased less in the ranolazine group vs. the control group. Ranolazine decreased c[Ca2+] only during ischemia while NADH and FAD were not different during IR in the ranolazine vs. control groups. Throughout reperfusion LVP and CF were higher, and ventricular fibrillation was less frequent. Infarct size was smaller in the ranolazine group than in the control group. Mitochondria isolated from ranolazine-treated hearts had mild resistance to permeability transition pore (mPTP) opening and less cytochrome c release than control hearts. Ranolazine may provide functional protection of the heart during IR injury by reducing cCa2+ and mCa2+ loading secondary to its effect to block the late Na+ current. Subsequently it indirectly reduces O2·- emission, preserves bioenergetics, delays mPTP opening, and restricts loss of cytochrome c, thereby reducing necrosis and apoptosis.
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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.