title: Intramural optical mapping of V(m) and Ca(i)2+ during long-duration ventricular fibrillation in canine hearts.
abstract: Intramural gradients of intracellular Ca(2+) (Ca(i)(2+)) Ca(i)(2+) handling, Ca(i)(2+) oscillations, and Ca(i)(2+) transient (CaT) alternans may be important in long-duration ventricular fibrillation (LDVF). However, previous studies of Ca(i)(2+) handling have been limited to recordings from the heart surface during short-duration ventricular fibrillation. To examine whether abnormalities of intramural Ca(i)(2+) handling contribute to LDVF, we measured membrane voltage (V(m)) and Ca(i)(2+) during pacing and LDVF in six perfused canine hearts using five eight-fiber optrodes. Measurements were grouped into epicardial, midwall, and endocardial layers. We found that during pacing at 350-ms cycle length, CaT duration was slightly longer (by ≃10%) in endocardial layers than in epicardial layers, whereas action potential duration (APD) exhibited no difference. Rapid pacing at 150-ms cycle length caused alternans in both APD (APD-ALT) and CaT amplitude (CaA-ALT) without significant transmural differences. For 93% of optrode recordings, CaA-ALT was transmurally concordant, whereas APD-ALT was either concordant (36%) or discordant (54%), suggesting that APD-ALT was not caused by CaA-ALT. During LDVF, V(m) and Ca(i)(2+) progressively desynchronized when not every action potential was followed by a CaT. Such desynchronization developed faster in the epicardium than in the other layers. In addition, CaT duration strongly increased (by ∼240% at 5 min of LDVF), whereas APD shortened (by ∼17%). CaT rises always followed V(m) upstrokes during pacing and LDVF. In conclusion, the fact that V(m) upstrokes always preceded CaTs indicates that spontaneous Ca(i)(2+) oscillations in the working myocardium were not likely the reason for LDVF maintenance. Strong V(m)-Ca(i)(2+) desynchronization and the occurrence of long CaTs during LDVF indicate severely impaired Ca(i)(2+) handling and may potentially contribute to LDVF maintenance.
authors.affiliation: Department of Biomedical Engineering, University of Alabama, Birmingham, 35294, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Kong
authors.forename: Raymond E
authors.initials: RE
authors.lastname: Ideker
authors.forename: Vladimir G
authors.initials: VG
authors.lastname: Fast
mesh_terms: D000200:Action Potentials; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling; D002304:Cardiac Pacing, Artificial; D004285:Dogs; D004699:Endocardium / Q000378:metabolism / Q000503:physiopathology; D006339:Heart Rate; D006352:Heart Ventricles / Q000378:metabolism* / Q000503:physiopathology; D066298:In Vitro Techniques; D008297:Male; D009206:Myocardium / Q000378:metabolism; D010477:Perfusion; D010496:Pericardium / Q000378:metabolism / Q000503:physiopathology; D013997:Time Factors; D014693:Ventricular Fibrillation / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D056969:Voltage-Sensitive Dye Imaging
chemical_list: D002118:Calcium