title: Graded response and restitution hypotheses of ventricular vulnerability to fibrillation: insights into the mechanism of initiation of fibrillation.
abstract: According to the upper limit of vulnerability (ULV), failed defibrillation (DF) shocks reinitiate ventricular fibrillation (VF) by falling on the vulnerable period of one or more of the fibrillation wavefronts. The failed shock first induces reentry (stage I VF), which within few cycles degenerate to stage II VF. We developed 2 hypotheses of vulnerability that explain DF failure using isolated and intact in situ ventricles. Activation maps were constructed with high-resolution electrodes and action potential (AP) recorded with microelectrodes. According to the graded response (GR) hypothesis, reentry is formed when a critical shock strength induces a GR that transiently increases local refractoriness. The GR propagates and initiates distal regenerative activity that propagates around the site of block to reenter through it as it recovers. Ultrastrong shocks prevent reentry by converting unidirectional block to bidirectional block by excessive increase in refractoriness, a finding that supports the ULV hypothesis. In situ ventricle stimulus-induced termination of reentry and stage I VF (protective zone) could be explained by the GR hypothesis. The induced functional reentry with periods of 100 to 160 ms engages the steep (unstable) portion of the AP duration restitution curves (slope >1) that promotes meandering and breakup. This leads to transition from stage I to stage II VF (the restitution hypothesis). We conclude that the GR and restitution hypotheses provide an insight into the mechanism of ventricular vulnerability to fibrillation induced by a stimulus. These hypotheses provide a new paradigm for effective antifibrillatory strategies.
authors.affiliation: Department of Medicine, Cedars-Sinai Research Institute and UCLA School of Medicine, Los Angeles, California, USA.
authors.forename: H S
authors.initials: HS
authors.lastname: Karagueuzian
authors.forename: P S
authors.initials: PS
authors.lastname: Chen
mesh_terms: D000818:Animals; D016880:Anisotropy; D004285:Dogs; D004554:Electric Countershock; D004562:Electrocardiography; D006352:Heart Ventricles / Q000503:physiopathology; D008955:Models, Cardiovascular; D010496:Pericardium / Q000503:physiopathology; D012815:Signal Processing, Computer-Assisted; D013611:Tachycardia, Atrioventricular Nodal Reentry / Q000503:physiopathology / Q000628:therapy; D014693:Ventricular Fibrillation / Q000503:physiopathology* / Q000628:therapy