Alpha Adrenergic Agonists for CPR

In the United States alone, approximately 450,000 people yearly suffer a cardiac arrest outsidethe hospital. Less than 10% of these patients are discharged from the hospital alive, and of these,approximately 60% suffer some form of permanent neurologic injury. The poor resuscitation rates andneurologic outcome result in part from the low level of myocardial and cerebral blood flow and oxygendelivery generated during cardiopulmonary resuscitation (CPR). While epinephrine (an alpha 1,2;beta-1,2 adrenergic agonist) is currently used during CPR to enhance perfusion, it is unclear whatspecific adrenergic agonist components are required to optimize hemodynamics and minimize toxicity(i.e. increases on oxygen consumption and ventricular dysrhythmias) in this setting. Our specific aimis to synthesize adrenergic agonists that will maximally enhance myocardial and cerebral hemodynamics,resuscitation rates (without the development of hemodynamically significant ventricular dysrhythmias),and neurologic outcome following resuscitation from cardiac arrest.