There are at least 500,000 victims of cardiac arrest each year in the United States. In the majority of these patients, the initial rhythm is not ventricular fibrillation (VF) or ventricular tachycardia (VT), but is pulseless electrical activity (PEA) or asystole. The survival rates for VT/VF arrests average around 20%. The survival rates for PEA and asystolic arrests are much lower, however, and average only around 5%. There is a critical need, therefore, for improved resuscitation strategies, since each 1% increase in survival rate would result in approximately 5000 additional survivors. This critical need is most apparent with PEA arrests, since little is known about the pathophysiology or the optimal treatment of these arrests, especially when compared to VT/VF arrests. Defibrillation is the definitive treatment for VT/VF arrest, but is not indicated in PEA arrest. We present the novel hypothesis that most PEA arrests are due to failure of ventricular muscle from acute ischemia and/or hypoxia in a substrate where there has been chronic ischemia and/or hypoxia. This contrasts with most VT/VF arrests where acute ischemia causes VT/VF in a healthier substrate. We further hypothesize that this chronic ischemia and/or hypoxia induces preconditioning, which prevents or delays the occurrence of VF, resulting in PEA arrest. We hypothesize, therefore, that therapy for PEA arrests must be directed at reversing this profound ischemia and/or hypoxia, as well as mitigating reperfusion injury. Even though there may be preconditioning, such preconditioning may not be uniform. In addition, the already severe compromise of the metabolic status of the heart would make any degree of reperfusion injury more detrimental in PEA arrests than in VT/VF arrests. Therapy should, therefore, be directed at generating substantial blood flow during resuscitation, including the use of vasodilators, to reverse the profound ischemia that may be present. Methods for augmenting blood flow should include the use of improved external compression devices, which may be particularly useful for treating out-of-hospital arrests; and the use of extracorporeal systems, which may be particularly useful for in-hospital arrests. Controlled reperfusion, including post conditioning, may be necessary at the beginning of reperfusion to reduce reperfusion injury. Additional preservation strategies may also be useful, including intra-arrest hypothermia. Finally, we hypothesize that each of these strategies will have incremental and additive improvement in outcomes from PEA cardiac arrest. The goals of this project are to improve our understanding of the pathophysiology of PEA cardiac arrest, develop improved methods for augmenting blood flow during resuscitation, and also develop synergistic, improved strategies for mitigating the effects of the profound ischemia and/or hypoxia present in PEA arrest. These studies should provide new information and insights about the pathophysiology of PEA cardiac arrests, and may lead to substantial improvements in the now dismal outcomes from PEA cardiac arrests.

Public Health Relevance

There are at least 500,000 victims of cardiac arrest each year in the United States. Many of these arrests are due to pulseless electrical activity, in which ther is relatively normal electrical activity of the heart, but no effective heart contractions. Because survival from this type of cardiac arrest is so low, we are studying the mechanisms whereby pulseless electrical activity occurs, and we are also developing improved therapies for treating pulseless electrical activity, based on those mechanisms.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL126092-03
Application #
9178083
Study Section
Clinical and Integrative Cardiovascular Sciences Study Section (CICS)
Program Officer
Sopko, George
Project Start
2014-11-10
Project End
2018-10-31
Budget Start
2016-11-01
Budget End
2017-10-31
Support Year
3
Fiscal Year
2017
Total Cost
Indirect Cost
Name
Johns Hopkins University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21205
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Keller, Steven P; Halperin, Henry R (2015) Cardiac arrest: the changing incidence of ventricular fibrillation. Curr Treat Options Cardiovasc Med 17:392