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Endothelin(ET)-1 (ET-1) increases after myocardial infarction and may have effects on myocardial function. ET-1 has also been shown to affect the action potential (AP) which may be arrhythmogenic and predispose to ventricular fibrillation (VF). The effects of ET-2 and ET-3 are uncertain. We hypothesized that the ETs increase during acute ischemia and that plasma levels are predictive of ischemically induced VF. Thirty-four domestic swine underwent balloon occlusion of the proximal LAD coronary artery. Occlusion was confirmed angiographically. Venous samples were collected from the right atrium at baseline and at 5 min intervals for 30 min or until VF induction. ET-1, ET-2, and ET-3 were measured using ELISA. Changes in plasma concentrations were assessed using repeated measures ANOVA with Dunnett’s. A p < 0.05 was considered statistically significant. All animals had angiographic evidence of successful proximal LAD occlusion. ET-1 levels were significantly increased from a baseline at 20 min and remained elevated during 30 min of occlusion. ET-2 and ET-3 levels did not change from baseline values (figure, mean ± SE). VF occurred in 60% of animals. Peak ET-1 values were not significantly different between VF and non-VF animals (6.2 ± 2.2 vs. 4.8 ± 2.3 pg/mL). No single ET-1 value had a VF predictive value >50%. There is a significant increase in ET-1 level within 20 min of acute myocardial ischemia. Despite known effects of ET-1 on the AP, this increase did not correlate with the occurrence of VF.