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Electrical Remodelling (electrical + remodelling)

Distribution by Scientific Domains
Medical Sciences100%

Selected Abstracts

A Metabolic Mechanism For Cardiac K+ Channel Remodelling

CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 1-2 2002
George J Rozanski
SUMMARY 1. Electrical remodelling of the ventricle is a common pathogenic feature of cardiovascular disease states that lead to heart failure. Experimental data suggest this change in electrophysiological phenotype is largely due to downregulation of K+ channels involved in repolarization of the action potential. 2. Voltage-clamp studies of the transient outward current (Ito) in diabetic cardiomyopathy support a metabolic mechanism for K+ channel downregulation. In particular, Ito density is significantly increased in diabetic rat isolated ventricular myocytes treated in vitro with insulin or agents that activate pyruvate dehydrogenase. Recent data suggest this mechanism is not limited to diabetic conditions, because metabolic stimuli that upregulate Ito in diabetic rat myocytes act similarly in non- diabetic models of heart failure. 3. Depressed Ito channel activity is also reversed by experimental conditions that increase myocyte levels of reduced glutathione, indicating that oxidative stress is involved in electrical remodelling. Moreover, upregulation of Ito density by activators of glucose utilization is blocked by inhibitors of glutathione metabolism, supporting the premise that there is a functional link between glucose utilization and the glutathione system. 4. Electrophysiological studies of diabetic and non-diabetic disease conditions affecting the heart suggest Ito channels are regulated by a redox-sensitive mechanism, where glucose utilization plays an essential role in maintaining a normally reduced state of the myocyte. This hypothesis has implications for clinical approaches aimed at reversing pathogenic electrical remodelling in a variety of cardiovascular disease states. [source]

Atrial fibrillation: insights from clinical trials and novel treatment options

JOURNAL OF INTERNAL MEDICINE, Issue 6 2007
Y. Blaauw
Abstract., Blaauw Y, Crijns HJGM (University Hospital Maastricht, Maastricht, The Netherlands). Atrial fibrillation: insights from clinical trials and novel treatment options (Review). J Intern Med 2007; 262: 593,614. Atrial fibrillation (AF) is the most common encountered sustained arrhythmia in clinical practice. The last decade the result of large ,rate' versus ,rhythm' control trials have been published that have changed the current day practise of AF treatment. It has become clear that rate control is at least equally effective as a rhythm control strategy in ameliorating morbidity as well as mortality. Moreover, in each individual patient the risk of thromboembolic events should be assessed and antithrombotic treatment be initiated. There have also been great advances in understanding the mechanisms of AF. Experimental studies showed that as a result of electrical and structural remodelling of the atria, ,AF begets AF'. Pharmacological prevention of atrial electrical remodelling has been troublesome, but it seems that blockers of the renin angiotensin system, and perhaps statins, may reduce atrial structural remodelling by preventing atrial fibrosis. Clinical studies demonstrated that the pulmonary veins exhibit foci that can act as initiator and perpetuator of the arrhythmia. Isolation of the pulmonary veins using radiofrequency catheter ablation usually abolishes AF. The most promising advances in the pharmacological treatment of AF include atrial specific antiarrhythmic drugs and direct thrombin inhibitors. In the present review we will describe the results of recent experimental studies, discuss the latest clinical trials, and we will focus on novel treatment modalities. [source]

A Metabolic Mechanism For Cardiac K+ Channel Remodelling

CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 1-2 2002
George J Rozanski
SUMMARY 1. Electrical remodelling of the ventricle is a common pathogenic feature of cardiovascular disease states that lead to heart failure. Experimental data suggest this change in electrophysiological phenotype is largely due to downregulation of K+ channels involved in repolarization of the action potential. 2. Voltage-clamp studies of the transient outward current (Ito) in diabetic cardiomyopathy support a metabolic mechanism for K+ channel downregulation. In particular, Ito density is significantly increased in diabetic rat isolated ventricular myocytes treated in vitro with insulin or agents that activate pyruvate dehydrogenase. Recent data suggest this mechanism is not limited to diabetic conditions, because metabolic stimuli that upregulate Ito in diabetic rat myocytes act similarly in non- diabetic models of heart failure. 3. Depressed Ito channel activity is also reversed by experimental conditions that increase myocyte levels of reduced glutathione, indicating that oxidative stress is involved in electrical remodelling. Moreover, upregulation of Ito density by activators of glucose utilization is blocked by inhibitors of glutathione metabolism, supporting the premise that there is a functional link between glucose utilization and the glutathione system. 4. Electrophysiological studies of diabetic and non-diabetic disease conditions affecting the heart suggest Ito channels are regulated by a redox-sensitive mechanism, where glucose utilization plays an essential role in maintaining a normally reduced state of the myocyte. This hypothesis has implications for clinical approaches aimed at reversing pathogenic electrical remodelling in a variety of cardiovascular disease states. [source]