This revised biomedical partnership proposal from the Univ. of Chicago and Argonne National Lab aims to develop an intra-arrest cooling system for field use by paramedics during cardiac arrest and is directly responsive to the NIH PULSE Workshop calling for new resuscitation methods. Two prototype microparticle slurries have been developed: one saline-based for intravascular use and another perfluorocarbon-based for pulmonary use. These slurries contain high percentages of small (100mum) highly fluid, smooth ice particles with 8 times the cooling capacity of the same liquid (0 degrees C) without ice. In initial swine studies saline slurry resulted in very rapid brain and heart cooling (>1 degree C every 2 minutes) during cardiac arrest with only chest compression to produce circulation, far superior to any external cooling techniques. Moreover, adverse effects of 30 minutes exposure to perfluorocarbon slurry instilled into the lungs of normal animals (not in cardiac arrest) were mild and improved with time. Animals survived unassisted for 48 hours with A-a gradients not significantly different from controls. Thus, creating an optimal cooling method with minimal adverse effects appears a realistic goal.
Specific aims and milestones include: (i) bioengineering and developing two microparticulate slurries for pulmonary and intravenous use, (ii) using these slurries to optimize """"""""intra-arrest"""""""" cooling rates of the heart and brain of animals during cardiac arrest, (iii) describing and minimizing adverse effects of slurries, and finally (iv) testing whether slurry cooling to 2 different levels of intra-arrest low-flow cooling will improve survival in a swine model of cardiac arrest. Unlike any existing method, paramedics could use this cooling method after failed defibrillation in efforts to delay additional heart and brain damage until full reperfusion can occur. An international advisory committee of noted resuscitation experts will advise the project and many wish to test the slurries in their home laboratories after completion of these aims, increasing the potential impact of this work.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
7R01HL067630-05
Application #
7089887
Study Section
Special Emphasis Panel (ZRG1-CVA (01))
Program Officer
Goldberg, Suzanne H
Project Start
2002-08-05
Project End
2009-07-31
Budget Start
2006-08-01
Budget End
2009-07-31
Support Year
5
Fiscal Year
2006
Total Cost
$895,402
Indirect Cost
Name
University of Pennsylvania
Department
Emergency Medicine
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Lampe, Joshua W; Yin, Tai; Bratinov, George et al. (2018) Effect of compression waveform and resuscitation duration on blood flow and pressure in swine: One waveform does not optimally serve. Resuscitation 131:55-62
Choi, Jaewoo; Yin, Tai; Shinozaki, Koichiro et al. (2018) Comprehensive analysis of phospholipids in the brain, heart, kidney, and liver: brain phospholipids are least enriched with polyunsaturated fatty acids. Mol Cell Biochem 442:187-201
Zhang, Wei; Tam, Jonathan; Shinozaki, Koichiro et al. (2018) Increased Survival Time With SS-31 After Prolonged Cardiac Arrest in Rats. Heart Lung Circ :
Kim, Junhwan; Yin, Tai; Shinozaki, Koichiro et al. (2017) Potential of lysophosphatidylinositol as a prognostic indicator of cardiac arrest using a rat model. Biomarkers 22:755-763
Kim, Junhwan; Yin, Tai; Shinozaki, Koichiro et al. (2016) DHA-supplemented diet increases the survival of rats following asphyxia-induced cardiac arrest and cardiopulmonary bypass resuscitation. Sci Rep 6:36545
Kim, Junhwan; Villarroel, José Paul Perales; Zhang, Wei et al. (2016) The Responses of Tissues from the Brain, Heart, Kidney, and Liver to Resuscitation following Prolonged Cardiac Arrest by Examining Mitochondrial Respiration in Rats. Oxid Med Cell Longev 2016:7463407
Shinozaki, Koichiro; Lampe, Joshua W; Kim, Junhwan et al. (2016) The effects of early high-volume hemofiltration on prolonged cardiac arrest in rats with reperfusion by cardiopulmonary bypass: a randomized controlled animal study. Intensive Care Med Exp 4:25
Kim, Junhwan; Lampe, Joshua W; Yin, Tai et al. (2015) Phospholipid alterations in the brain and heart in a rat model of asphyxia-induced cardiac arrest and cardiopulmonary bypass resuscitation. Mol Cell Biochem 408:273-81
Lampe, Joshua W; Bratinov, George; Weiland 3rd, Theodore R et al. (2015) Volume infusion cooling increases end-tidal carbon dioxide and results in faster and deeper cooling during intra-cardiopulmonary resuscitation hypothermia induction. Intensive Care Med Exp 3:37
Patil, Kaustubha D; Halperin, Henry R; Becker, Lance B (2015) Cardiac arrest: resuscitation and reperfusion. Circ Res 116:2041-9

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