Abstract 15679: Escalating Doses of β-Estradiol Fail to Improve Resuscitation Outcomes in a Rat Model of Ventricular Fibrillation and Closed Chest Resuscitation
Background: In previous studies, β-estradiol given in bolus dose (1 mg/kg) failed to improve resuscitability and survival in a rat model of VF and closed chest resuscitation. Given that β-estradiol could exert adverse effects at high plasma levels, we conducted additional studies in the same rat model investigating incremental steady doses of β-estradiol.
Methods:VF was induced in 40 male retired breeder Sprague-Dawley rats and left untreated for 8 minutes after which resuscitation was attempted by an 8 minute interval of chest compression and electrical shocks. Rats were randomized 1:1:1:1 to receive 0.9% NaCl (control) or β-estradiol at incremental concentrations designed to attain a plasma level of 100, 102, or 104 nM during chest compression. The infusions were started with chest compression and maintained for 15 minutes post-resuscitation with the investigators blind to the assignment. Rats that restored spontaneous circulation were observed for 180 minutes post-resuscitation.
Results: Cardiac activity was restored in all control rats but in only 8 rats in each β-estradiol group. Survival was reduced in β-estradiol groups, attaining statistical significance when the β-estradiol groups were combined (Figure). Myocardial and hemodynamic function analyzed by two way repeated measures ANOVA showed statistically significant differences only in mean aortic pressure and between the β-estradiol 102 nM group and control (115±19 vs 89±16 mmHg, p=0.015).
Conclusions: The present study not only failed to identify a β-estradiol dose that could be beneficial for resuscitation from VF but suggested that β-estradiol could be instead detrimental and compromise survival when given during the resuscitation effort.
- © 2012 by American Heart Association, Inc.