Endothelin-1 vasoconstriction during swine cardiopulmonary resuscitation improves coronary perfusion pressures but worsens postresuscitation outcome

Abstract

Background - Vasoconstriction during cardiopulmonary resuscitation (CPR) improves Coronary perfusion pressure (CPP) and thereby outcome. The combination of endothelin-1 (ET-l) plus epinephrine improved CPP during CPR compared with epinephrine alone in a canine cardiac arrest model. The effect of the combination on outcome variables, such as successful resuscitation and survival, has not been investigated. Methods and Results - Twenty-seven swine were randomly provided with 1 mg epinephrine (Epi group) or 1 mg epinephrine plus 0.1 mg ET-1 (ET-1 group) during a prolonged ventricular fibrillatory cardiac arrest. ET-1 resulted in substantially superior aortic relaxation pressure and CPP during CPR. These hemodynamic improvements tended to increase initial rates of restoration of spontaneous circulation (8 of 10 versus 8 of 17, P=0.12). However, continued intense vasoconstriction from ET- 1 led to higher aortic diastolic pressure and very narrow pulse pressure after resuscitation. The mean pulse pressure 1 hour after resuscitation was 7±8 mm Hg with ET-1 versus 24±1 mm Hg with Epi, P<0.01. Most importantly, the postresuscitation mortality was dramatically higher in the ET-1 group (6 of 8 versus 0 of 8 in the Epi group, P<0.01). Conclusions - These data establish that administration of ET-1 during CPR can result in worse postresuscitation outcome. The intense vasoconstriction from ET-1 improved CPP during CPR but had detrimental effects in the postresuscitation period.