Effects of endothelin-1 on resuscitation rate during cardiac arrest

Objectives: Endothelin-1 (ET-1) is a potent peripheral and coronary artery vasoconstrictor and has been shown to improve coronary perfusion pressure (CPP) during cardiac arrest. The effect of ET-1 on return of spontaneous circulation (ROSC) following cardiac arrest has not been studied. Our hypothesis was that ET-1 does not improve ROSC from cardiac arrest when compared to placebo. Methods: A total of 11 immature swine were used in this laboratory study. Animals were randomized to receive 300 μg ET-1 and standard dose epinephrine (SDE) or placebo and SDE during arrest. After a 10- min period of no-flow ventricular fibrillation (VF), CPR was performed for 3 min followed by ET-1/SDE or placebo/SDE administration. Following drug administration, standard ACLS was followed with SDE given every 3 min. Aortic pressure was monitored during resuscitation. ROSC was defined as any perfusing rhythm with a systolic pressure greater than 60 mmHg for 60 s. Animals received post-ROSC care as needed for 2 h post-ROSC. CPP and ROSC were analyzed using repeated measures ANOVA and Fischer's exact test respectively. P < 0.05 was considered significant. Results: Pre-arrest variables and CPP prior to ET-1 administration were not different between groups. Following ET-1 administration, CPP was significantly increased at all time points in ET-1/SDE versus placebo/SDE animals. ROSC was achieved in 1/5 (20%) ET-1/SDE versus 1/6 (16.7%) placebo/SDE animals (P > 0.05). The resuscitated ET-1/SDE animal survived 6.5 min compared to 120 min for the resuscitated placebo/SDE animal. Conclusions: In our study, ET-1 administration during cardiac arrest increases CPP but does not improve ROSC.