title: Role of calcium and the calcium channel in the initiation and maintenance of ventricular fibrillation.
abstract: The cellular events during the initiation and maintenance of ventricular fibrillation (VF) are poorly understood. We developed a nonischemic, isolated, perfused rabbit Langendorff preparation in which sustained VF could be induced by alternating current (AC) and which allowed changes in perfusate composition. We also used Na(+)-K+ pump inhibition (10 microM ouabain or K(+)-free perfusate) to induce VF. AC stimulation or Na(+)-K+ pump inhibition always initiated VF. Calcium channel blockade by verapamil or nitrendipine uniformly inhibited the initiation of VF in both models. During Na(+)-K+ pump inhibition, 1) VF was prevented by calcium channel blockade, despite evidence of Ca2+ overload, and 2) abolition of spontaneous sarcoplasmic reticulum-generated cytosolic Ca2+ oscillations by ryanodine or Na+ channel blockade with tetrodotoxin did not prevent VF initiation. Lowering extracellular [Ca2+] to 80 microM uniformly prevented the initiation of VF due to Na(+)-K+ pump inhibition but not that due to AC stimulation. VF maintenance also was studied using 1) reduction in perfusate [Ca2+], 2) blockade of Ca2+ channels, or 3) electrical defibrillation. Decreasing the perfusate [Ca2+] to 80 microM resulted in defibrillation during VF whether induced by AC or Na(+)-K+ pump inhibition. Verapamil or nitrendipine also resulted in defibrillation regardless of the initiation method. Electrical defibrillation was successful only in AC-induced VF. The results demonstrate that VF can be initiated and maintained in a nonischemic rabbit Langendorff preparation. The data suggest that increases in slow channel Ca2+ flux, as opposed to increases in cytosolic Ca2+ per se, were necessary for the initiation and maintenance of VF. The data, however, do not exclude an important role for cytosolic Ca2+ in the modulation of VF.
authors.affiliation: Johns Hopkins University School of Medicine, National Institute on Aging, Baltimore, Md.
authors.forename: J C
authors.initials: JC
authors.lastname: Merillat
authors.forename: E G
authors.initials: EG
authors.lastname: Lakatta
authors.forename: O
authors.initials: O
authors.lastname: Hano
authors.forename: T
authors.initials: T
authors.lastname: Guarnieri
mesh_terms: D000818:Animals; D001693:Biological Transport, Active; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism*; D004554:Electric Countershock; D066298:In Vitro Techniques; D009568:Nitrendipine / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism; D011817:Rabbits; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D014693:Ventricular Fibrillation / Q000378:metabolism* / Q000628:therapy; D014700:Verapamil / Q000494:pharmacology
chemical_list: D015220:Calcium Channels; D009568:Nitrendipine; D014700:Verapamil; D011188:Potassium; D002118:Calcium