tretinoin and Arrhythmias--Cardiac

Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) hold great promise for studying inherited cardiac arrhythmias and developing drug therapies to treat such arrhythmias. Unfortunately, until now, action potential (AP) measurements in hiPSC-CMs have been hampered by the virtual absence of the inward rectifier potassium current (

Topics: Action Potentials; Arrhythmias, Cardiac; Atrial Function; Cell Differentiation; Heart Ventricles; Humans; Induced Pluripotent Stem Cells; Myocytes, Cardiac; Patch-Clamp Techniques; Potassium; Potassium Channels, Inwardly Rectifying; Tretinoin

Nickel, a metal commonly found in battery plants and welding factories, has potential cardiotoxicity, while all-trans retinoid acid (atRA) can promote cardiovascular repair and myocardial recovery. The purpose of this study was to investigate whether atRA could prevent cardiotoxicity induced by nickel both in vitro and in vivo. In the study, a rat myocardial cell line (H9c2) exposed to different concentrations of nickel chloride (NiCl(2)) displayed apoptotic features accompanied by reactive oxygen species generation. In addition, NiCl(2) also caused obvious apoptosis and systolic dysfunction in primary myocardial cells. Treatment with atRA efficiently attenuated the cytotoxicities triggered by NiCl(2) as it significantly mitigated ROS generation and decreased MAP kinases activity in NiCl(2)-treated cardiomyocytes. Additionally, NiCl(2) exposure caused obvious arrhythmia in Sprague-Dawley rats with the maximum tolerance dose of NiCl(2) between 2 and 3mg/kg. A combinational intragastric administration of 40mg/kg atRA can partially reverse NiCl(2)-induced arrhythmia in rats. Our results suggested that atRA might have therapeutic potential in alleviating the adverse effects of nickel on the cardiovascular system.

Topics: Animals; Apoptosis; Arrhythmias, Cardiac; Cell Line; Dose-Response Relationship, Drug; MAP Kinase Signaling System; Myocytes, Cardiac; Nickel; Protective Agents; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; Tretinoin

Retinoic acid syndrome is a novel complication of therapy with all-trans retinoic acid (ATRA) in patients with acute promyelocytic leukemia (APML). Primarily the syndrome consists of fever and respiratory distress. Additional features include weight gain, oedema over lower extremities, pleural or pericardial effusion and hypotension. We report electrophysiological changes in a 16 year old patient with acute promyelocytic leukemia following treatment with ATRA. Such an unusual complication is a rarity and to the best of our knowledge has not been previously reported.

Topics: Adolescent; Antineoplastic Agents; Arrhythmias, Cardiac; Dexamethasone; Dyspnea; Female; Glucocorticoids; Humans; Leukemia, Promyelocytic, Acute; Pericardial Effusion; Syndrome; Tretinoin

Topics: Adult; Arrhythmias, Cardiac; Embryonic and Fetal Development; Female; Fetal Diseases; Fetus; Humans; Leukemia, Promyelocytic, Acute; Maternal-Fetal Exchange; Permeability; Placenta; Pregnancy; Pregnancy Complications, Neoplastic; Treatment Outcome; Tretinoin

Previous studies have shown that free polyunsaturated fatty acids (PUFA) reduce the excitability of cardiac myocytes and exert antiarrhythmic effects. Therefore, we hypothesized that retinoic acid (RA, vitamin A acid), which has structural characteristics similar to those of PUFA, may have similar antiarrhythmic effects. To test this hypothesis, we used an isolated, spontaneously beating, neonatal rat cardiac myocyte preparation to examine the effects of RA, added to the perfusion solution, on the cell contraction and arrhythmias induced by isoproterenol (ISO) or lysophosphatidylcholine (LPC). All-trans-RA (10-20 microM) induced a marked and reversible reduction in the contraction rate of the cell in 2-5 min without changing the amplitude of the contractions. Superfusion of the myocytes with either ISO (3 microM) or LPC (5 microM) induced sustained tachyarrhythmias characterized by spasmodic contractures and fibrillation. Addition of 15-20 microM all-trans-RA to the perfusion solution effectively prevented as well as terminated the arrhythmias induced by ISO and LPC. Furthermore, in a whole-animal model of arrhythmia in which the left anterior descending coronary artery (LAD) of the anesthetized rat was occluded for 15 min followed by reperfusion, both the incidence and severity of ventricular tachycardia and fibrillation (VT, VF) were significantly reduced during the ischemic and reperfusion periods by intravenous infusion of all-trans-RA. In contrast, other analogues, including retinol and retinal, and other fat-soluble vitamins, including vitamin D, E, and K, did not have such effects. Our results demonstrate that all-trans-RA can produce antiarrhythmic effects similar to those of PUFA, suggesting a novel role of RA as a potential antiarrhythmic agent.

Topics: Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Cells, Cultured; Isoproterenol; Lysophosphatidylcholines; Myocardial Contraction; Myocardial Ischemia; Myocardial Reperfusion; Rats; Rats, Sprague-Dawley; Tretinoin

Topics: Acne Vulgaris; Adolescent; Arrhythmias, Cardiac; Humans; Male; Quinidine; Tretinoin