Abstract 69: Endothelin-1 Levels Predict Response to Exogenous Epinephrine in a Porcine Ischemic Ventricular Fibrillation Cardiac Arrest Model
Background: Plasma endothelin-1 (ET-1) increases in the ischemically induced VF swine model of cardiac arrest and affects outcome. ET-1 regulates arterial tonus and may alter the vascular response to pressors. We hypothesized that ET-1 attenuates the hemodynamic response to epinephrine in the ischemic VF arrest model.
Methods: 51 swine underwent percutaneous LAD occlusion. Seven minutes after the onset of ischemic VF, standard CPR was initiated. If VF persisted after 3 shocks, 1 mg of epinephrine was given and resuscitation continued in accordance with guidelines. Before occlusion and at 5 minute intervals, blood samples were collected from the right atrium. Plasma ET-1 was assayed with ELISA and multivariate logistic regression analysis was used to compare peak ET-1 levels with positive coronary perfusion pressure response of >20 mmHg following epinephrine administration.
Results: Sixteen animals (31%) failed to achieve a positive epinephrine response. Return of spontaneous circulation was observed in only 1/16 (6.3%) of these epinephrine non-responders and 20/35 (57.1%) of epinephrine responders (p=0.0006). The mean peak ET-1 level was 3.9pg/mL (95% CI 2.8–5.1) in non-responders and 2.2pg/mL (95% CI 1.4–3.0) in responders (difference 1.7, 95% CI 0.4–3.1, p=0.01). In univariate logistic regression analysis, a 1 pg/ml difference in peak ET-1 value was associated with an odds ratio (OR) for an epinephrine response of 0.67 (95% CI 0.46 – 0.97, p=0.03). The associated probability curve is given in Figure 1. A cutoff for peak ET-1 of 3.7pg/mL demonstrated an overall accuracy of 75% for predicting CPP response (sensitivity 90%, specificity 44%).
Conclusions: Peak ET-1 levels predict a lack of a hemodynamic response to epinephrine during treatment of cardiac arrest during ischemic VF. ET-1 attenuates the arterial pressor response to epinephrine and may be one mechanism accounting for a variable response to epinephrine administered during resuscitation.
- © 2010 by American Heart Association, Inc.