The effects of graded doses of endothelin-1 on coronary perfusion pressure and vital organ blood flow during cardiac arrest

Abstract

Background: Endothelin-1 (ET-1) is a potent vasoconstrictor and has been shown to improve coronary perfusion pressure (CPP) during arrest. The effects of ET-1 on organ blood flow during arrest have not been extensively studied. Objective: To investigate the effects of ET-1 on myocardial and cerebral blood flow during cardiac arrest. Methods: Sixty immature swine were anesthetized and instrumented. The animals were randomized to receive one of three doses of ET-1 (50, 150, or 300 μg) or placebo with/without standard- dose epinephrine (SDE) during cardiac arrest. After a 10-minute period of no- flow ventricular fibrillation (VF), cardiopulmonary resuscitation (CPR) was performed for 3 minutes, followed by drug administration. Placebo or SDE was given every 3 minutes. Myocardial and cerebral blood flow was measured using a fluorescent microsphere technique. Results: Prearrest and CPR variables were not different between groups. Beginning 4 minutes after giving 300 μg ET-1 with or without SDE, CPP was significantly increased compared with SDE alone. Total myocardial blood flow following ET-1 administration was no different than myocardial blood flow following SDE alone. Cerebral blood flow increased 3.5 minutes after administration of 300 μg ET-1 with SDE and reached significance 9.5 minutes after drug administration when compared with SDE alone [92.5 (48.8-117.9) vs 15.6 (7.7-23) mL/min/100 g]. Conclusions: Three hundred μg ET-1 with SDE increases CPP and improves cerebral blood flow but does not improve myocardial blood flow during cardiac arrest. The peripheral effects of ET-1 significantly improve CPP and cerebral blood flow, but myocardial blood flow is not increased due to coronary vasoconstriction.