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The goals of this study were to quantify the effects of epinephrine on myocardial and cerebral blood flow during conventional cardiopulmonary resuscitation (CPR) and CPR with simultaneous chest compression-ventilation and to test the hypothesis that epinephrine would improve myocardial and cerebral blood flow by preventing collapse of intrathoracic arteries and by vasoconstricting other vascular beds, thereby increasing perfusion pressures. Cerebral and myocardial blood flow were measured by the radiolabeled microsphere technique, which we have previously validated during CPR. We studied the effect of epinephrine on established arterial collapse during CPR with simultaneous chest compression-ventilation with the abdomen bound or unbound. Epinephrine reversed arterial collapse, thereby eliminating the systolic gradient between aortic and carotid pressures and increasing cerebral perfusion pressure and cerebral blood flow while decreasing blood flow to other cephalic tissues. Epinephrine produced higher cerebral and myocardial perfusion pressures during CPR with simultaneous chest compression-ventilation when the abdomen was unbound rather than bound because abdominal binding increased intracranial and venous pressures. In other experiments we compared the effect of epinephrine on blood flow during 1 hr of either conventional CPR or with simultaneous chest compression-ventilation with the abdomen unbound. Epinephrine infusion during conventional CPR produced an average cerebral blood flow of 15 ml/min-100 g (41 + 15% of control) and an average myocardial blood flow of 18 mI/min 100 g (15 ± 8% of control). In our previous studies, cerebral and myocardial blood flow were less than 3 ±+ 1 % of control during conventional CPR without epinephrine. Although flows during CPR with simultaneous chest compression-ventilation without epinephrine were initially higher than those during conventional CPR, arterial collapse developed after 20 min, limiting cerebral and myocardial blood flow. The use of epinephrine throughout 50 min of CPR with simultaneous chest compression-ventilation maintained cerebral blood flow at 22 + 2 ml/min 100 g (73 ± 25% control) and left ventricular blood flow at 38 ± 9 ml/min 100 g (28 ± 8% control). The improved blood flows with epinephrine correlated with improved electroencephalographic activity and restoration of spontaneous circulation. The mechanisms responsible for the increased brain and myocardial blood flow with epinephrine include the prevention of arterial collapse and the intense vasoconstriction of other vascular beds, which prevents the run off of blood into these tissues and preferentially increases cerebral and myocardial perfusion pressures. We conclude that epinephrine substantially improves cerebral and myocardial blood flow during both conventional CPR and CPR with simultaneous chest compression-ventilation and that the combined use of epinephrine and CPR with simultaneous chest compression-ventilation with the abdomen unbound maintains high levels of blood flow to the ...