alternan and Arrhythmias--Cardiac

Essentially all previous research on alternans has been restricted to normal myocardium, whereas sudden cardiac death (SCD) occurs most commonly in patients with ventricular dysfunction (i.e., heart failure), which is associated with marked disruption of proteins responsible for normal calcium cycling in myocytes. Several lines of evidence from studies in normal hearts suggest a link between impaired calcium cycling which characterizes ventricular mechanical dysfunction and impaired calcium cycling that is responsible for alternans. In normal myocardium, cells which exhibit the slowest calcium cycling, and not the slowest repolarization, are most susceptible to alternans. Decreased expression of key calcium cycling proteins is observed in alternans-prone cells. Sarcoplasmic reticulum ATPase (SERCA2a) expression is decreased, suggesting a mechanism for the slower sarcoplasmic reticulum (SR) calcium reuptake observed in alternans-prone cells. In addition, diminished ryanodine receptor (RyR) function leading to abnormal calcium release from the SR is also linked to cellular alternans. Although impaired contractile function clearly predisposes to SCD, the mechanisms linking mechanical to electrophysiological dysfunction in the heart are unclear. We propose that cellular calcium alternans may be an important mechanism linking mechanical dysfunction to cardiac arrhythmogenesis.

Topics: Animals; Arrhythmias, Cardiac; Biomarkers; Calcium; Death, Sudden, Cardiac; Glucans; Humans

Atrial fibrillation (AF) is the most common arrhythmia in humans, yet; treatment has remained sub-optimal due to poor understanding of the underlying mechanisms. Cardiac alternans precede AF episodes, suggesting an important arrhythmia substrate. Recently, we demonstrated ventricular SERCA2a overexpression suppresses cardiac alternans and arrhythmias. Therefore, we hypothesized that atrial SERCA2a overexpression will decrease cardiac alternans and arrhythmias.. Adult rat isolated atrial myocytes where divided into three treatment groups 1) Control, 2) SERCA2a overexpression (Ad.SERCA2a) and 3) SERCA2a inhibition (Thapsigargin, 1μm). Intracellular Ca2+ was measured using Indo-1AM and Ca2+ alternans (Ca-ALT) was induced with a standard ramp pacing protocol.. As predicted, SR Ca2+ reuptake was enhanced with SERCA2a overexpression (p< 0.05) and reduced with SERCA2a inhibition (p<0.05). Surprisingly, there was no difference in susceptibility to Ca-ALT with either SERCA2a overexpression or inhibition when compared to controls (p = 0.73). In contrast, SERCA2a overexpression resulted in increased premature SR Ca2+ (SCR) release compared to control myocytes (28% and 0%, p < 0.05) and concomitant increase in SR Ca2+ load (p<0.05). Based on these observations we tested in-vivo atrial arrhythmia inducibility in control and Ad.SERCA2a animals using an esophageal atrial burst pacing protocol. There were no inducible atrial arrhythmias in Ad.GFP (n = 4) animals though 20% of Ad.SERCA2a (n = 5) animals had inducible atrial arrhythmias (p = 0.20).. Our findings suggest that unlike the ventricle, SERCA2a is not a key regulator of cardiac alternans in the atrium. Importantly, SERCA2a overexpression in atrial myocytes can increase SCR, which may be arrhythmogenic.

Topics: Animals; Arrhythmias, Cardiac; Atrial Fibrillation; Brugada Syndrome; Calcium; Cardiac Conduction System Disease; Gene Expression Regulation; Glucans; Heart Atria; Heart Conduction System; Humans; Myocytes, Cardiac; Patch-Clamp Techniques; Rats; Sarcoplasmic Reticulum Calcium-Transporting ATPases; Thapsigargin

Topics: Arrhythmias, Cardiac; Electrocardiography; Geriatrics; Glucans; Heart Block; Heart Diseases; Tachycardia

Topics: Arrhythmias, Cardiac; Brugada Syndrome; Cardiac Complexes, Premature; Cardiac Conduction System Disease; Electrocardiography; Glucans; Heart Conduction System; Humans; Hypokalemia

Topics: Arrhythmias, Cardiac; Electrocardiography; Glucans; Humans

Topics: Arrhythmias, Cardiac; Electrocardiography; Glucans; Humans

Topics: Arrhythmias, Cardiac; Electrocardiography; Glucans; Humans

Topics: Arrhythmias, Cardiac; Carcinoma, Bronchogenic; Cardiac Tamponade; Electrocardiography; Glucans; Humans; Radiography, Thoracic

Topics: Arrhythmias, Cardiac; Electrocardiography; Exudates and Transudates; Glucans; Heart; Humans; Neoplasm Metastasis; Neoplasms; Pericardial Effusion; Pericardium

Topics: Arrhythmias, Cardiac; Cardiac Tamponade; Electrocardiography; Exudates and Transudates; Glucans; Heart; Humans; Pericardium; Serositis; Subclavian Vein; Thrombophlebitis

Topics: Arrhythmias, Cardiac; Electromyography; Glucans; Heart; Pericardial Effusion; Pericardium

Topics: Arrhythmias, Cardiac; Disease; Electrocardiography; Glucans; Heart Diseases; Humans; Pericardial Effusion; Pericardium

Topics: Arrhythmias, Cardiac; Disease; Glucans; Heart Block; Heart Diseases; Humans; Medical Records; Pericardial Effusion; Pericardium

Topics: Arrhythmias, Cardiac; Child; Glucans; Humans; Infant; Myocarditis

Topics: Arrhythmias, Cardiac; Electrocardiography; Epinephrine; Glucans

Topics: Animals; Arrhythmias, Cardiac; Cardiovascular Physiological Phenomena; Dogs; Glucans; Heart Rate; Humans; Pulse

Topics: Animals; Arrhythmias, Cardiac; Dogs; Glucans; Sympathomimetics

Topics: Arrhythmias, Cardiac; Disease; Electrocardiography; Glucans; Heart Diseases; Humans; Pericardial Effusion; Pericardium

Topics: Arrhythmias, Cardiac; Electrocardiography; Glucans; Heart; Humans; Pericardiocentesis; Pericardium; Stomach Neoplasms

Topics: Arrhythmias, Cardiac; Coronary Disease; Glucans; Heart Diseases; Humans; Hypertension

Topics: Arrhythmias, Cardiac; Electrocardiography; Glucans; Humans

Topics: Arrhythmias, Cardiac; Glucans; Humans

Topics: Arrhythmias, Cardiac; Glucans; Heart Block; Mephentermine

Topics: Arrhythmias, Cardiac; Electrocardiography; Glucans; Humans

Topics: Arrhythmias, Cardiac; Electrodiagnosis; Glucans

Topics: Arrhythmias, Cardiac; Glucans; Heart Failure; Heart Ventricles; Humans

Topics: Arrhythmias, Cardiac; Disease; Electrocardiography; Glucans; Heart; Heart Diseases; Humans; Pericardium

Topics: Arrhythmias, Cardiac; Cardiovascular Abnormalities; Cardiovascular System; Glucans; Heart; Humans

Topics: Aged; Arrhythmias, Cardiac; Electrocardiography; Glucans; Humans

Topics: Arrhythmias, Cardiac; Disease; Glucans; Heart Diseases; Humans; Pericardial Effusion; Pericardium

Topics: Arrhythmias, Cardiac; Glucans; Heart Failure; Humans

Topics: Arrhythmias, Cardiac; Diagnosis, Differential; Glucans; Heart Rate; Humans

Topics: Arrhythmias, Cardiac; Cardiovascular Physiological Phenomena; Electromyography; Glucans; Heart Rate; Humans; Pulse

Topics: Arrhythmias, Cardiac; Ballistocardiography; Glucans; Humans

Topics: Arrhythmias, Cardiac; Glucans; Humans; Posture

Topics: Arrhythmias, Cardiac; Glucans; Hemodynamics; Humans

Topics: Arrhythmias, Cardiac; Glucans; Humans

Topics: Arrhythmias, Cardiac; Glucans; Humans; Tachycardia, Ventricular

Topics: Arrhythmias, Cardiac; Electrocardiography; Glucans; Heart; Humans

Topics: Arrhythmias, Cardiac; Electrocardiography; Glucans; Humans

Topics: Arrhythmias, Cardiac; Digitalis; Glucans; Heart Rate; Humans; Tachycardia, Ventricular