New approaches for identifying antiarrhythmic drug targets.
Sudden cardiac death, secondary to ventricular fibrillation (VF), remains the leading cause of death in many developed countries. Substantial experimental and theoretical support exists for the idea that VF is caused by spiral wave re-entry. The initiation and subsequent break-up of spiral waves have been linked to electrical alternans, a phenomenon typically associated with a steeply sloped restitution relationship. Interventions that reduce the slope of the restitution relationship have been shown to prevent the induction of VF and to terminate existing VF in experimental models. These results suggest that electrical restitution may be a promising new target for antiarrhythmic therapies.
Robert F
RF
Gilmour
D000200:Action Potentials / Q000187:drug effects; D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000627:therapeutic use; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology; D002986:Clinical Trials as Topic; D016757:Death, Sudden, Cardiac / Q000517:prevention & control*; D004285:Dogs; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D000072237:ERG1 Potassium Channel; D004562:Electrocardiography / Q000187:drug effects; D051638:Ether-A-Go-Go Potassium Channels / Q000235:genetics / Q000502:physiology; D005822:Genetic Vectors / Q000235:genetics / Q000627:therapeutic use; D006329:Heart Conduction System / Q000187:drug effects*; D015640:Ion Channel Gating / Q000187:drug effects*; D008955:Models, Cardiovascular; D010766:Phosphorylation / Q000187:drug effects; D011188:Potassium / Q000378:metabolism; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D014161:Transduction, Genetic; D014693:Ventricular Fibrillation / Q000188:drug therapy* / Q000503:physiopathology
D000319:Adrenergic beta-Antagonists; D000889:Anti-Arrhythmia Agents; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; D015221:Potassium Channels; D011188:Potassium; D002118:Calcium