Hemorrhagic shock that leads to cardiovascular collapse does not respond well to conventional methods of cardiopulmonary resuscitation. Even when the source of bleeding can be controlled and circulation restored, cerebral ischemia lasting 5 minutes or longer results in severe brain damage. Overall survival remains about 5% despite aggressive surgical interventions and open chest cardiac resuscitation. Often the underlying injury is reparable but the patient dies of irreversible shock. In such patients, strategies to maintain cerebral and cardiac viability long enough to gain control of hemorrhage could be life saving. This requires an entirely new approach, with emphasis on rapid total body preservation, repair of injuries during metabolic arrest and delayed resuscitation. Currently, hypothermia is the most effective modality for preservation of cellular viability during periods of ischemia. However, its role in the setting of traumatic hemorrhage has not been established. We plan to use clinically relevant large animal models to test the therapeutic application of induced hypothermia following exsanguinating shock. LONG TERM HYPOTHESIS: Hypothermic arrest can be induced in the setting of traumatic lethal hemorrhagic shock to maintain organ viability during periods of total body ischemia. LONG TERM GOALS: Establish the optimal strategy for induction, maintenance and reversal of total body hypothermia in the setting of lethal uncontrolled hemorrhagic shock. Utilize the period of hypothermic arrest for repair of complex injuries.
SPECIFIC AIM 1 : Determine the optimal rate of induction and reversal of total body hypothermia.
Sub aim : Develop and utilize large animal cognitive function models to test neurologic outcome.
SPECIFIC AIM 2 : Establish the maximum depth and duration for which hypothermic metabolic arrest can be maintained with complete neurologic recovery.
Sub aim : Study the role of optimal a cellular organ preservation fluids in extending the duration of hypothermic metabolic arrest.
SPECIFIC AIM 3 : Determine the duration of uncontrolled hemorrhagic shock, prior to induction of hypothermic arrest, that is compatible with good neurologic outcome.
Sub aim 1 : Demonstrate that the hypothermic arrest period can be used to repair complex multiple organ injuries.
Sub aim 2 : Develop and test methods and techniques that can facilitate the induction of hypothermic arrest in the setting of traumatic shock.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
7R01HL071698-04
Application #
6921957
Study Section
Special Emphasis Panel (ZHL1-CSR-M (S1))
Program Officer
Liang, Isabella Y
Project Start
2002-09-30
Project End
2007-07-31
Budget Start
2005-09-01
Budget End
2007-07-31
Support Year
4
Fiscal Year
2005
Total Cost
$437,500
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
073130411
City
Boston
State
MA
Country
United States
Zip Code
02199
Alam, H B (2012) Translational barriers and opportunities for emergency preservation and resuscitation in severe injuries. Br J Surg 99 Suppl 1:29-39
Alam, Hasan B; Velmahos, George C (2011) New trends in resuscitation. Curr Probl Surg 48:531-64
Alam, Hasan B (2011) Advances in resuscitation strategies. Int J Surg 9:5-12
Alam, Hasan B; Duggan, Michael; Li, Yongqing et al. (2008) Putting life on hold-for how long? Profound hypothermic cardiopulmonary bypass in a Swine model of complex vascular injuries. J Trauma 64:912-22
Sailhamer, Elizabeth A; Chen, Zheng; Ahuja, Naresh et al. (2007) Profound hypothermic cardiopulmonary bypass facilitates survival without a high complication rate in a swine model of complex vascular, splenic, and colon injuries. J Am Coll Surg 204:642-53
Alam, Hasan B; Chen, Zheng; Li, Yongqing et al. (2006) Profound hypothermia is superior to ultraprofound hypothermia in improving survival in a swine model of lethal injuries. Surgery 140:307-14
Alam, Hasan B; Casas, Fernando; Chen, Zhang et al. (2006) Development and testing of portable pump for the induction of profound hypothermia in a Swine model of lethal vascular injuries. J Trauma 61:1321-9
Alam, Hasan B; Rhee, Peter; Honma, Kaneatsu et al. (2006) Does the rate of rewarming from profound hypothermic arrest influence the outcome in a swine model of lethal hemorrhage? J Trauma 60:134-46
Chen, Zhang; Chen, Huazhen; Rhee, Peter et al. (2005) Induction of profound hypothermia modulates the immune/inflammatory response in a swine model of lethal hemorrhage. Resuscitation 66:209-16
Taylor, M J; Rhee, P; Chen, Z et al. (2005) Design of preservation solutions for universal tissue preservation in vivo: demonstration of efficacy in preclinical models of profound hypothermic cardiac arrest. Transplant Proc 37:303-7

Showing the most recent 10 out of 12 publications