Abstract 15214: β-Estradiol Fails to Reverse Post-Resuscitation Myocardial Dysfunction in Male Sprague-Dawley Rats
Background: In two previous series of experiments, conducted in a rat model of VF and closed chest resuscitation, β-estradiol failed to demonstrate beneficial effects on resuscitability or survival regardless of the dose used. However, a β-estradiol dose aimed at attaining a plasma level of 102 nM during closed chest resuscitation was associated with higher mean aortic pressure post-resuscitation. This observation prompted us to examine whether such dose could help reverse post-resuscitation myocardial dysfunction when used in conjunction with dobutamine; a hypothesis based on recent studies showing that erythropoietin (which activates similar protective pathways as estrogen) reversed post-resuscitation myocardial dysfunction in the same rat model.
Methods: VF was electrically induced in 12 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 delivery of electrical shocks. Rats were randomized 1:1 to receive a continuous right atrial infusion of β-estradiol 3,17-disulfate dipotassium salt aimed at attaining a plasma level of 102 nM during chest compression or 0.9% NaCl control. The infusion was started coincident with chest compression and maintained for 15 minutes post-resuscitation. A dobutamine infusion (15 µg/kg·min-1) was continuously delivered through a 180 minute post-resuscitation interval. The investigators were blind to the assignment.
Results: Dobutamine provided inotropic support securing hemodynamic stability throughout the post-resuscitation interval. However, in contrast to the previously observed effect of erythropoietin, β-estradiol had no additional effects on left ventricular or hemodynamic function (Table).
Conclusions: β-estradiol failed to help reverse post-resuscitation myocardial dysfunction suggesting activation of cell mechanisms different than those activated by erythropoietin.
- © 2012 by American Heart Association, Inc.