Although almost 400,000 patients suffer cardiac arrest each year in the United States, average survival rates following Cardiopulmonary Resuscitation (CPR) have averaged <5% for the last 5 decades. Regrettably, manual standard CPR is inherently inefficient. Recent efforts have been shifted to reduce the ischemic damage to the brain and heart by increasing circulation with mechanical adjuncts and post arrest therapeutic hypothermia (TH). A method which promotes normalization of vital organ blood flow and simultaneously allows for intra-CPR TH could have the greatest impact on neurologically intact survival in cardiac arrest since the first description of chest compressions 50 years ago. In our grant proposal we describe the first favorable results and suggest research that needs to be performed on a new method of CPR with the potential to be used in all patients with cardiac arrest and maintain heart and brain viability for prolonged periods regardless of the presenting rhythm. We hypothesize that by using a combination of sodium nitroprusside (SNP), a potent vasodilator, and mechanical CPR adjuncts we can effectively normalize CPR-generated blood flow to the heart and brain. We further hypothesize that the pharmacologically induced cutaneous vasodilatation, combined with high forward blood flow, will facilitate intra- CPR heat exchange and TH. Our pilot data indicate that an achievable goal of this proposal is to conclusively show that elimination of thoracic and cerebral vasoconstriction with a potent vasodilator combined with non- invasive mechanical adjuncts that promote cardiac output and increase sub-diaphragmatic vascular resistance, will normalize and maintain vital organ perfusion during CPR. The pharmacological cutaneous vasodilatation will expedite heat exchange with surface cooling so that clinically valuable TH can be achieved before return to spontaneous circulation. Our proposed research will: 1.) identify the optimal combination of mechanical adjuncts and the optimal dose of sodium nitroprusside (SNP) to optimize flow and survival after cardiac arrest, 2.) demonstrate that SNP CPR offers similar benefits in different cardiac arrest models, and 3.) demonstrate that SNP CPR can provide immediate and effective intra-CPR therapeutic hypothermia.

Public Health Relevance

Due to inherent ineffectiveness of standard CPR a new more efficient method is needed to significantly improve resuscitation outcomes and long term neurological intact survival. We propose a new method which includes a potent arterial dilator (sodium nitroprusside or SNP) and non invasive mechanical adjuncts that increase cardiac output and re-direct flow to the heart and brain. The proposed combination can efficiently be used for initiation of therapeutic hypothermia during CPR and preliminary studies have demonstrated a distinctive advantage compared to standard CPR in all resuscitation related outcomes.

Agency
National Institute of Health (NIH)
Type
Research Project (R01)
Project #
5R01HL108926-04
Application #
8676557
Study Section
Clinical and Integrative Cardiovascular Sciences Study Section (CICS)
Program Officer
Sopko, George
Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of Minnesota Twin Cities
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
City
Minneapolis
State
MN
Country
United States
Zip Code
55455
Garcia, Santiago; Drexel, Todd; Bekwelem, Wobo et al. (2016) Early Access to the Cardiac Catheterization Laboratory for Patients Resuscitated From Cardiac Arrest Due to a Shockable Rhythm: The Minnesota Resuscitation Consortium Twin Cities Unified Protocol. J Am Heart Assoc 5:
Debaty, Guillaume; Matsuura, Timothy R; Bartos, Jason A et al. (2015) Sodium nitroprusside-enhanced cardiopulmonary resuscitation facilitates intra-arrest therapeutic hypothermia in a porcine model of prolonged ventricular fibrillation. Crit Care Med 43:849-55
Debaty, Guillaume; Metzger, Anja; Rees, Jennifer et al. (2015) Enhanced perfusion during advanced life support improves survival with favorable neurologic function in a porcine model of refractory cardiac arrest. Crit Care Med 43:1087-95
Bartos, Jason A; Matsuura, Timothy R; Sarraf, Mohammad et al. (2015) Bundled postconditioning therapies improve hemodynamics and neurologic recovery after 17 min of untreated cardiac arrest. Resuscitation 87:7-13
Riess, Matthias L; Matsuura, Timothy R; Bartos, Jason A et al. (2014) Anaesthetic Postconditioning at the Initiation of CPR Improves Myocardial and Mitochondrial Function in a Pig Model of Prolonged Untreated Ventricular Fibrillation. Resuscitation 85:1745-51
Bartos, Jason A; Debaty, Guillaume; Matsuura, Timothy et al. (2014) Post-conditioning to improve cardiopulmonary resuscitation. Curr Opin Crit Care 20:242-9
Sideris, Georgios; Magkoutis, Nikolaos; Sharma, Alok et al. (2014) Early coronary revascularization improves 24h survival and neurological function after ischemic cardiac arrest. A randomized animal study. Resuscitation 85:292-8
Bartos, Jason A; Yannopoulos, Demetris (2013) Novelties in pharmacological management of cardiopulmonary resuscitation. Curr Opin Crit Care 19:417-23
Yannopoulos, Demetris; Segal, Nicolas; Matsuura, Timothy et al. (2013) Ischemic post-conditioning and vasodilator therapy during standard cardiopulmonary resuscitation to reduce cardiac and brain injury after prolonged untreated ventricular fibrillation. Resuscitation 84:1143-9
Segal, Nicolas; Matsuura, Timothy; Caldwell, Emily et al. (2012) Ischemic postconditioning at the initiation of cardiopulmonary resuscitation facilitates functional cardiac and cerebral recovery after prolonged untreated ventricular fibrillation. Resuscitation 83:1397-403

Showing the most recent 10 out of 16 publications