Effects of rotigaptide, a gap junction modifier, on defibrillation energy and resuscitation from cardiac arrest in rabbits.
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.
Zhong
Jing-quan
JQ
Department of Medicine, University of Toronto and Division of Cardiology, St. Michael's Hospital, 30 Bond Street, Toronto, Ontario, Canada.
Laurent
Gabriel
G
So
Petsy Pui-Sze
PP
Hu
Xudong
X
Hennan
James K
JK
Dorian
Paul
P
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*
D018031:Connexin 43; D009842:Oligopeptides; C029579:antiarrhythmic peptide; C477643:rotigaptide