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Exercise duration, time to onset of angina, and time to 1-mm ST-segment depression significantly increased with increased dose.

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Revascularization needs to be discussed in patients with symptoms of occlusion or large ischaemic areas.

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Hindleg glucose uptake was calculated as the A-V glucose difference multiplied by average FBF.

We next determined the effect of 10 μM ranolazine on hippocampal I Na during voltage protocols designed to selectively engage fast inactivation.

HF using isotopic tracers and found no differences in myocardial glucose, lactate, or fatty acid metabolism compared with normal dogs.

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In subsequent experiments from the same laboratory, Chandler et al reproduced these findings and determined that the improvement in left ventricular performance was not associated with an increase in myocardial oxygen consumption (MV̇ o 2) compared with an intravenous infusion of dobutamine that improved left ventricular performance to a similar extent but was associated with a significant increase in MV̇ o 2 requirements.

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Rehabilitation hospitals or units may provide the most extensive and comprehensive care and should be a consideration for patients who have good potential for recovery and can participate in and tolerate aggressive therapy.

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Early withdrawal from the study because of adverse events occurred in 2, 1, 1, and 11 patients, respectively.

QTc interval and electrocardiographic changes by type of shift work.

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Relationship between nonsustained ventricular tachycardia after non-ST-elevation acute coronary syndrome and sudden cardiac death: observations from the metabolic efficiency with ranolazine for less ischemia in non-ST-elevation acute coronary syndrome-thr.

Ranolazine improves exercise parameters with no detectable effect on heart rate and blood pressure in patients with chronic stable angina pectoris.

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You agree to consult a physician or professional healthcare provider for your medical and prescription drug care.

Reactivation of unstable angina after discontinuance of heparin has been documented among subjects not receiving concomitant aspirin therapy.

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Over time, coronary-related microvascular disease can increase the risk of heart failure and heart attacks.

Patients with more symptomatic heart disease, including moderate angina, may be guided by an exercise stress test as a means of assessing risk and reassuring the patient.

Ask your health care provider any questions you may have about how to use ranolazine.

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Compared with placebo, ranolazine significantly reduced the weekly average frequency of self-reported angina episodes (primary endpoint) and nitroglycerin use.

We and others have previously reported that microvascular recruitment is associated with increased muscle delivery of insulin and glucose use (; ) due to increased microvascular surface area.

Yet ranolazine was effective in abating this form of diastolic dysfunction.

The two aims of the pharmacological management of stable CAD patients are to obtain relief of symptoms and to prevent CV events.

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With regard to LPL, functional LPL present on the capillary endothelial cell surface is initially synthesized as an inactive monomeric proenzyme in the endoplasmic reticulum (ER) of the cardiac myocyte itself (for review, see Ref.

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However, drug-induced QT-interval prolongation does not always progress to TdP.

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Ranolazine at clinically relevant concentrations of 5 and 10 μM prolonged the duration of the action potential (APD 90, duration of the action potential at 90% of repolarization) in atria but had minimal or no effect on APD in ventricular myocardium (Burashnikov et al.

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Ranolazine infusion did not alter the plasma insulin concentration ().

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QTc prolongation for the 2 drugs ().

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All study participants underwent comprehensive 2-dimensional (2D) echocardiographic examination with Doppler and tissue Doppler imaging (TDI) at rest and at peak bicycle exercise using a commercially available exercise ergometer (MPI; Medical Positioning, Kansas City, MO) at both the baseline and 3-month study visits.

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Dronedarone is incorporated into hydrogels that adhere to the tissues to which the anti-arrhythmic drugs are to be delivered and then biodegrade.

Shown are representative action potentials and summary data of the effect on APD 50 and APD 90 in coronary-perfused atrial and ventricular preparations stimulated at a cycle of length (CL) of 500 ms (millisecond or msec).

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The event prevention is optimally achieved by the prescription of antiplatelet agents and statins.

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RANEXA 750 mg twice daily increases the plasma concentrations of a single dose of immediate release metoprolol (100 mg), a CYP2D6 substrate, by 80% in extensive CYP2D6 metabolizers with no need for dose adjustment of metoprolol.

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Validity and Reliability of Seattle Angina Questionnaire Japanese Version in Patients With Coronary Artery Disease.

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The antianginal efficacy of ranolazine was examined in several patient subsets in the MARISA and CARISA trials.

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Continue to take the tablets unless you are advised otherwise by your doctor.

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Surprisingly, these mice also showed an increased cardiac glucose uptake and oxidation, a phenotype opposite of PPARα overexpression.

Tell all of your health care providers that you take this drug.

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Although ranolazine is not approved for the treatment of type 2 diabetes, in post hoc analyses of pivotal angina trials, ranolazine was associated with reductions in percent glycosylated hemoglobin (HbA 1c) in subjects with type 2 diabetes.

Concomitant QT-prolonging drugs, major P-gp inhibitors, and CYP3A4 inducers and inhibitors including: cyclosporine, rifampin, rifabutin, rifapentine, phenobarbital, phenytoin, carbamazepine, St.

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Changes from baseline in postprandial serum insulin 3-h AUC were similar between ranolazine and placebo.

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Ranolazine has also been demonstrated to be superior to amiodarone in reducing the incidence of AF following coronary artery bypass graph surgery and in combination therapy to improve conversion from recent onset AF over amiodarone alone.

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Long-term prognostic value of exercise echocardiography compared with exercise 201Tl, ECG, and clinical variables in patients evaluated for coronary artery disease.

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Further evidence of inherited long QT syndrome gene mutations in antiarrhythmic drug-associated torsades de pointes.

The control provided by ranolazine and dronedarone of atrial rhythm (i.

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Comparison of effectiveness of ranolazine plus amiodarone versus amiodarone alone for conversion of recent-onset atrial fibrillation.

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Several other treatment strategies including b-blockers, angiotensin-converting enzyme inhibitors, ranolazine, l-arginine, statin drugs and potentially estrogen replacement therapy have been shown to relieve anginal symptoms as well as improve vascular function.

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Effects were independent of potassium concentration.

N-terminal pro-B-type natriuretic peptide after high-dose chemotherapy: a marker predictive of cardiac dysfunction?

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Epidemiological studies show that obese people have a decrease in life expectancy and greater mortality from cardiovascular disease (, ) and a greater risk for developing HF ().

Collaborative overview of randomised trials of antiplatelet therapy-I: Prevention of death, myocardial infarction, and stroke by prolonged antiplatelet therapy in various categories of patients.

Steady state was also assessed by comparing means for C 48h, C 72h and C 96h using a mixed effects ANOVA model and untransformed and log, transformed data.

This process requires FACS, which consumes the equivalent of two molecules of ATP as the reaction releases AMP and pyrophosphate.

By selecting peer-reviewed literature in Pubmed and Cochrane Library, this review provides an overview on ranolazine pharmacology and efficacy, focusing on recent evidence suggesting its usefulness in management of primary MVA.

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This site is an invaluable resource for pharmacists who need to assess the QT-prolongation risk of medications.

Neal Barnard wrote a compelling editorial, in the American Medical Association's Journal of Ethics.

RANEXA may be used with other medicines that are used for heart problems and blood pressure control.

Insulin antagonizes AMP-activated protein kinase activation by ischemia or anoxia in rat hearts, without affecting total adenine nucleotides.

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DTE was not significantly affected by either ranolazine (5 μM) or dronedarone (10 μM) in either atria or ventricles at pacing CLs of 500 and 300 ms ( FIG.

Additionally, the placebo-corrected change from baseline in total and incremental 3-h glucose AUCs derived from MMTTs were significantly decreased in the ranolazine group at week 12 and remained decreased at week 24.

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Your heart muscle needs a constant supply of oxygen.

Chronic stable angina is the most common manifestation of coronary heart disease and it results from the imbalance between myocardial oxygen supply and demand due to reduction in coronary blood flow.

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D) Number of action potentials evoked during the 4 seconds of depolarizing current injection.

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Heparin and the low-molecular-weight heparins are often used to lower the risk that unstable angina will progress to myocardial infarction.

Impaired left ventricular relaxation and increased left ventricular end-diastolic pressure are early manifestations of myocardial ischemia, caused in part by calcium overload.

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Moreover, an increase in or addition of an anti-anginal drug was less frequent (ranolazine 10.

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Synergism between K-rasVal12 and mutant Apc accelerates murine large intestinal tumourigenesis.

Fentanyl plasma concentrations may be elevated, increasing the pharmacologic effects and risk of toxicity.

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Ranolazine may be taken with or without food.

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Diuretics may indirectly increase the risk of TdP by causing the excretion of potassium and magnesium.

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Higher doses were associated with an increased risk of TdP.

Traditional therapies for ischemia aim at restoring the balance between mitochondrial ATP production and breakdown by reducing the need for ATP via suppression of heart rate, blood pressure and cardiac contractility, or by increasing oxygen delivery via increased myocardial blood flow.

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The antianginal drug trimetazidine shifts cardiac energy metabolism from fatty acid oxidation to glucose oxidation by inhibiting mitochondrial long-chain 3-ketoacyl coenzyme A thiolase".

Together, these 2 findings point toward ranolazine as an attractive antianginal agent for patients with chronic angina and impaired glucose metabolism.

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