| Description |
Sudden cardiac arrest (SCA) is a leading killer in the United States. A large number of patients experience SCA outside of hospitals where there is an inherent delay in treatment due to slow first response times. In the out-of-hospital setting, ventricular fibrillation (VF)-induced SCA (VF-SCA) is the most common context in which the event manifests. VF leads to chaotic electrical and hence contractile function of the heart resulting in loss of cardiac output causing ischemia. Left untreated, electrical activity rapidly deteriorates, culminating in complete electrical failure or asystole. Survival rates for patients found in asystole are a mere 1%: asystole is a death sentence. Despite the high event and death rates of VF-SCA, little is known concerning the mechanisms of electrical failure. This dissertation represents the first concerted effort to understand the pathophysiology of electrical failure. The work contained herein can be divided into three projects. These projects were conducted in whole animal and isolated whole heart models of VFSCA. The first is a detailed examination of the complex patterns of electrical failure in VF-SCA. I found a highly complex pattern of electrical failure spanning the intra- and interchamber heterogeneities in three-dimensions. Second, I investigated the contributions of two canonical yet untested theories of electrical failure during VF-SCA: hyperkalemia and ATP-sensitive potassium channel (KATP) opening. I reached the surprising conclusion that neither hyperkalemia nor KATP opening-individually or combined-can explain the pattern of electrical failure in VF-SCA. Third, I investigated the effect of increasing metabolic demand on electrical failure during VF-SCA through increased p-adrenergic stimulation and excitation rate. The findings point toward a necessity to reexamine current resuscitation protocols. Specifically, the use of epinephrine (an α-and β-adrenergic agonist) may promote electrical failure during treatment of VF-SCA leading to increased mortality. |
