title: Endothelin-1 attenuates the hemodynamic response to exogenous epinephrine in a porcine ischemic ventricular fibrillation cardiac arrest model.
abstract: Endothelin-1 (ET-1) increases in the ischemically induced ventricular fibrillation (VF) swine model of cardiac arrest and affects outcome by potentially attenuating the hemodynamic response to epinephrine. Fifty-one swine underwent percutaneous left anterior descending occlusion. Seven minutes postonset of ischemic VF, cardiopulmonary resuscitation (CPR) was initiated. If VF persisted after 3 shocks, 1 mg of epinephrine was given. ET-1 (collected at baseline and every 5 min until VF onset) was assayed with ELISA. Bayesian multivariate logistic regression analysis compared peak ET-1 levels with the binary outcome of a positive coronary perfusion pressure response of >20 mmHg following epinephrine. Sixteen animals (31%) failed to achieve a positive response. Restoration of spontaneous circulation (ROSC) was observed in 1/16 (6.3%) of epinephrine nonresponders and 20/35 (57.1%) of epinephrine responders (P = 0.0006). The median peak ET-1 level was 2.71 pg/mL [interquartile range (IQR) 1.06-4.40] in nonresponders and 1.69 pg/mL (IQR 0.99-2.35) in responders. ET-1 levels were inversely associated with epinephrine response with a median posterior odds ratio (OR) of a coronary perfusion pressure response of 0.72 (95% confidence interval [CI] 0.48-1.06) for each one-unit increase in ET-1 and a probability that the associated OR is <1 of 0.95. Peak ET-1 levels predict a lack of a hemodynamic response to epinephrine during treatment of cardiac arrest during ischemic VF.
authors.affiliation: Division of Cardiology, Department of Medicine, University of Chicago, Chicago, Illinois 60637, USA. ashah5@uchicago.edu
authors.forename: Atman P
authors.initials: AP
authors.lastname: Shah
authors.forename: Scott T
authors.initials: ST
authors.lastname: Youngquist
authors.forename: Christian D
authors.initials: CD
authors.lastname: McClung
authors.forename: Joseph L
authors.initials: JL
authors.lastname: Thomas
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Tzvetkova
authors.forename: Mohammed A
authors.initials: MA
authors.lastname: Hanif
authors.forename: John P
authors.initials: JP
authors.lastname: Rosborough
authors.forename: James T
authors.initials: JT
authors.lastname: Niemann
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D019332:Endothelin-1 / Q000494:pharmacology*; D004837:Epinephrine / Q000627:therapeutic use*; D006323:Heart Arrest / Q000097:blood / Q000188:drug therapy*; D006439:Hemodynamics / Q000187:drug effects*; D008297:Male; D017202:Myocardial Ischemia / Q000097:blood / Q000188:drug therapy*; D013552:Swine; D014693:Ventricular Fibrillation / Q000097:blood / Q000188:drug therapy*
chemical_list: D019332:Endothelin-1; D004837:Epinephrine