On average, >90% of patients who suffer from a cardiac arrest die. Nearly all die unexpectedly fromthis leading cause of death, in part, because the essential components of standard CPR (S-CPR):manual chest compressions at a rate of 100/min, 1 to 1.5 inches in depth and positive pressureventilations, are an inherently inefficient process, providing less than 25% of normal blood flow to theheart and brain. Despite intensive research, little or no improvement in outcomes has been observedfor over half a century. This application builds upon our new understanding of ways to optimize bloodflow to the heart and brain during CPR and protect these organs from reperfusion injury. It promises toprovide new hope for patients who suffer from sudden cardiac death. The proposed research isfocused on demonstrating proof of concept that reducing or preventing reperfusion injury by utilizing abolus dose of anesthetic during the initiation of CPR is both feasible and critical to markedlyenhancing survival with favorable neurological function after cardiac arrest. Building upon recent andsignificant advances in the treatment of cerebral and cardiac ischemia, where controlled reperfusionhas been shown to strikingly reduce stroke and infarct size in patients with cerebral vascular eventsand myocardial infarction, we have recently administered a bolus dose of sevoflurane during the firstthree minutes of CPR in a pig model of prolonged untreated cardiac arrest. The results have beenstriking: after 15 minutes of untreated ventricular fibrillation, performing CPR with a bolus dose ofsevoflurane during the first three minutes of circulation in conjunction with a means to optimize bloodflow to the heart and brain during CPR has normalized brain and heart function < 24-hours afterarrest. These exciting observations contradict what was previously thought impossible; to restore fulllife in the setting of prolonged absence of flow and severe metabolic derangement. This novelapproach that significantly reduces and in some cases prevents reperfusion injury may result in anovel and clinically important method of CPR that is easy to implement by EMS personnel and in thehome. It provides the promise, based upon sound physiological principles and concepts, to markedlyimprove neurologically intact survival in patients that have heretofore never been possible toresuscitate. In this application we propose to further explore these findings. In the current applicationwe propose to a) demonstrate preclinical proof-of-concept that early administration of inhaledanesthetic for reperfusion injury protection will result in superior hemodynamics and survival withfavorable neurological outcomes in established animal models of prolonged (15 minutes) ventricularfibrillation cardiac arrest with and without bystander CPR and pulseless electrical activity, and b)design a device capable of administering a bolus dose of sevoflurane to provide a means to provideprotection from reperfusion injury available to EMS BLS providers. If successful, this therapy will resultin saving >10,000 more Americans each year from out of hospital cardiac arrest and a similar numberof in-hospital survivors based upon the superior blood flow and the ability afforded by PC to protectthe brain and heart from reperfusion injury during CPR.
Thesaurus Terms: Adopted;American;American Heart Association;Anesthetics;Animal Model;Animals;Applications Grants;Base;Basic Life Support;Blood;Blood Circulation;Blood Flow;Blood Vessels;Body Part;Bolus Infusion;Brain;Breathing;Cardiac;Cardiology;Caring;Cause Of Death;Cerebrum;Chest;Clinical;Clinical Trials;Complex;Conditioning;Data;Death, Sudden, Cardiac;Design;Devices;Disease;Disodium Salt Nitroprusside;Dose;Electric Impedance;Emergency Service/First Responder;Emergency Situation;Employee Strikes;Environmental Air Flow;Epinephrine;Event;Family Suidae;Foundations;Heart;Heart Arrest;Heart Function;Hemodynamics;Home Environment;Hospitals;Hour;Human Resources;Improved;Individual;Infarction;Injury;Intravenous;Ischemia;Life;Life Support Care;Literature;Manuals;Medical;Metabolic;Methods;Modeling;Molecular;Morbidity - Disease Rate;Mortality Vital Statistics;Myocardial;Myocardial Infarction;Nervous System Physiology;Neurological Outcome;Neurology;Novel;Novel Strategies;Organ;Outcome;Outcome Forecast;Patients;Pharmaceutical Preparations;Phase 1 Study;Physiological;Physiology;Pre-Clinical;Pressure;Prevent;Process;Provider;Public Health Medicine (Field);Public Health Relevance;Recovery;Reperfusion Injury;Reperfusion Therapy;Research;Resistance;Resuscitation;Series;Sevoflurane;Small Business Innovation Research Grant;Sodium;Sound;Stroke;Survivors;System;Technology;Testing;Therapeutic Target;Time;Translating;Transplantation;United States;Vasoconstrictor Agents;Vasodilator Agents;Ventricular Fibrillation;Western World;
