title: Effects of rotigaptide, a gap junction modifier, on defibrillation energy and resuscitation from cardiac arrest in rabbits.
abstract: The gap junction modifier Rotigaptide (ZP123), which promotes cellular coupling, was hypothesized to decrease defibrillation thresholds during prolonged ventricular fibrillation (VF). Thirty-two New Zealand white rabbits were randomized to receive saline (control, n = 16) or Rotigaptide (n = 16). Following 4 min of untreated VF, biphasic defibrillation shocks were applied through chest wall patches, starting either at 300 volts (V) (n = 16) or 500 V (n = 16), with 200 V increasing steps to 900 V in case of shock failure. Rotigaptide significantly decreased defibrillation voltage requirements (average cumulative voltage of all shocks: 1206 +/- 709 V in control group vs. 844 +/- 546 V in treated group, P = .002). Rotigaptide had no effect on heart rate, QRS duration, QT interval, ventricular effective refractory period, monophasic action potential duration or on connexin 43 density using immunofluorescence. Rotigaptide improves the ability to defibrillate after untreated VF.
authors.affiliation: Department of Medicine, University of Toronto and Division of Cardiology, St. Michael's Hospital, 30 Bond Street, Toronto, Ontario, Canada.
authors.forename: Jing-quan
authors.initials: JQ
authors.lastname: Zhong
authors.forename: Gabriel
authors.initials: G
authors.lastname: Laurent
authors.forename: Petsy Pui-Sze
authors.initials: PP
authors.lastname: So
authors.forename: Xudong
authors.initials: X
authors.lastname: Hu
authors.forename: James K
authors.initials: JK
authors.lastname: Hennan
authors.forename: Paul
authors.initials: P
authors.lastname: Dorian
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D018031:Connexin 43 / Q000378:metabolism; D004195:Disease Models, Animal; D004554:Electric Countershock / Q000379:methods; D004558:Electric Stimulation / Q000379:methods; D004562:Electrocardiography; D005455:Fluorescent Antibody Technique / Q000379:methods; D017629:Gap Junctions / Q000187:drug effects* / Q000502:physiology; D006323:Heart Arrest / Q000503:physiopathology / Q000628:therapy*; D006339:Heart Rate / Q000187:drug effects; D007275:Injections, Intravenous; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D009842:Oligopeptides / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D011817:Rabbits; D011897:Random Allocation; D012151:Resuscitation / Q000379:methods; D014693:Ventricular Fibrillation / Q000503:physiopathology / Q000628:therapy*
chemical_list: D018031:Connexin 43; D009842:Oligopeptides; C029579:antiarrhythmic peptide; C477643:rotigaptide