Circulation, Vol 73, 224-226, Copyright © 1986 by American Heart Association
JW Hammon and JA Oates
The occurrence of ventricular fibrillation after occlusion of the
circumflex coronary artery in the conscious dog was examined as one
preparation for sudden cardiac death arising from coronary artery disease.
The incidence of ventricular fibrillation after after circumflex occlusion
was reduced from 53% to 6% (p less than .01) by the infusion of
prostacyclin in doses that do not alter cardiac output or peripheral
resistance. This effect of prostacyclin led to the evaluation of two
structurally different inhibitors of thromboxane synthase in this
preparation; RO 22-4679 and U-63557A reduced ventricular fibrillation by
82% and 100%, respectively (p less than .05). The inhibition of ventricular
fibrillation by U-63557A was abrogated by pretreatment with indomethacin,
suggesting that a metabolite of the endoperoxide that accumulated during
thromboxane synthase inhibition was responsible for the protection from
ventricular fibrillation.
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